European Heart Rhythm Association (EHRA)
position paper on arrhythmia management and
device therapies in endocrine disorders
endorsed by Asia Pacific Heart Rhythm Society
(APHRS) and Latin American Heart Rhythm
Society (LAHRS)
Bulent Gorenek (Chair)1 Giuseppe Boriani2 Gheorge-Andrei Dan3
Laurent Fauchier4 Guilherme Fenelon5 He Huang6 Gulmira Kudaiberdieva78
Gregory YH Lip910 Rajiv Mahajan11 Tatjana Potpara12 Juan David Ramirez13
Marc A Vos14 and Francisco Marin (Co-Chair)15
ESC Scientific Document Group Carina Blomstrom-Lundqvist16 Aldo Rinaldi17
Maria Grazia Bongiorni18 Elena Sciaraffia19 Jens Cosedis Nielsen20
Thorsten Lewalter21 Shu Zhang22 Oswaldo Gutierrez23 Abdel Fuenmayor24
1Eskisehir Osmangazi University Eskisehir Turkey 2Cardiology Division Department of Diagnostics Clinical and Public Health Medicine University of Modena and ReggioEmilia Policlinico di Modena Modena Italy 3University of Medicine and Pharmacy ldquoCarol Davilardquo Colentina University Hospital Bucharest Romania 4Centre HospitalierUniversitaire Trousseau et Universite Francois Rabelais Tours France 5Hospital Israelita Albert Einstein S~ao Paulo Brazil 6Renmin Hospital of Wuhan University WuhanChina 7Adana Turkey 8Center for Postgraduate Education and Research Bishkek Kyrgyzstan 9Institute of Cardiovascular Sciences University of Birmingham Birmingham UK10Aalborg Thrombosis Research Unit Department of Clinical Medicine Aalborg University Aalborg Denmark 11The University of Adelaide Lyell McEwin Hospital RoyalAdelaide Hospital and SAHMRI Adelaide Australia 12School of Medicine Belgrade University Cardiology Clinic Clinical Centre of Serbia Belgrade Serbia 13ClinicaCardioVid Medellın Antioquia Colombia 14Umc Utrecht Utrecht Netherlands 15HU Virgen de la Arrixaca Murcia Spain 16Department of Medical Science andCardiology Uppsala University Uppsala Sweden 17St Thomasrsquo Hospital London UK 18Santa Chiara University Hospital of Pisa Pisa Italy 19Uppsala University HospitalUppsala Sweden 20Aarhus University Hospital Aarhus Denmark 21Peter Osypka Heart Center Munich Germany 22Beijing Fuwai Hospital Beijing China 23HospitalClinica Bblica San Jose Costa Rica and 24Electrophysiology and Arrhythmia Section Cardiovascular Research Institute University Hospital of The Andes Avenida 16 deSeptiembre Merida 5101 Venezuela
Received 19 February 2018 editorial decision 22 February 2018 accepted 25 February 2018
Endocrine disorders are associated with various tachyarrhythmias including atrial fibrillation (AF) ventricular tachy-cardia (VT) ventricular fibrillation (VF) and bradyarrhythmias Along with underlying arrhythmia substrate electro-lyte disturbances glucose and hormone levels accompanying endocrine disorders contribute to development ofarrhythmia Arrhythmias may be life-threatening facilitate cardiogenic shock development and increase mortalityThe knowledge on the incidence of tachy- and bradyarrhythmias clinical and prognostic significance as well as theirmanagement is limited it is represented in observational studies and mostly in case reports on management ofchallenging cases It should be also emphasized that the topic is not covered in detail in current guidelinesTherefore cardiologists and multidisciplinary teams participating in care of such patients do need the evidence-based or in case of limited evidence expert-opinion based recommendations how to treat arrhythmias using con-temporary approaches prevent their complications and recurrence in patients with endocrine disorders In recog-nizing this close relationship between endocrine disorders and arrhythmias the European Heart RhythmAssociation (EHRA) convened a Task Force with representation from Asia-Pacific Heart Rhythm Society (APHRS)
Corresponding author Tel thorn905424312483 E-mail address bulentgorenekcom
Published on behalf of the European Society of Cardiology All rights reserved VC The Author(s) 2018 For permissions please email journalspermissionsoupcom
Europace (2018) 0 1ndash30 EHRA POSITION PAPERdoi101093europaceeuy051
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and Sociedad Latinoamericana de Estimulacion Cardıaca y Electrofisiologıa (SOLAECE) with the remit of compre-hensively reviewing the available evidence and publishing a joint consensus document on endocrine disorders andcardiac arrhythmias and providing up-to-date consensus recommendations for use in clinical practice
Keywords Endocrine disorders bull Arrhythmias bull Atrial fibrillation bull Ventricular arrhythmias bull Cardiac implantableelectronic device bull Pacemaker bull Implantable cardioverter-defibrillator bull Catheter ablation bull Diabetes
bull Thyroid disorders bull Hyperthyroidism bull Hypothyroidism bull Pheochromocytoma bull Growth hormonedysfunction bull Hyperaldosteronism bull Adrenal insufficiency bull Parathyroid disease bull Stroke bull Oralanticoagulation bull EHRA position paper
Table of Contents
Introduction 2Evidence review 2
Mechanisms and pathophysiology of cardiac arrhythmias in endocrinedisorders 2
Management of arrhythmias in specific endocrine disorders 3Pancreas dysfunction 3
Diabetes mellitus 3Thyroid dysfunction 10
Hyperthyroidism 10Hypothyroidism 11Amiodarone-induced thyroid dysfunction 14
Pheochromocytoma 18Growth hormone dysfunction 19
Acromegaly 19Growth hormone deficiency 19
Diseases of adrenal cortex 20Hyperaldosteronism 21Adrenal insufficiency 20
Parathyroid disease 21Sex hormones-related differences in the risk of arrhythmias 21
Stroke risk assessment and prevention of arrhythmias associated withendocrine disorders 22
Catheter ablation of arrhythmias associated with endocrine disorders 23Device-based therapy of arrhythmias in patients with endocrine
disorders 23Current research gaps ongoing trials and future directions 24
Introduction
However the ultimate judgement on the care of a specific patientmust be made by the healthcare provider and the patient in light of allindividual factors presented
Evidence reviewThis document was prepared by the Task Force with representationfrom EHRA APHRS and SOLAECE and peer-reviewed by official ex-ternal reviewers representing EHRA HRS APHRS and SOLAECETheir members made a detailed literature review weighing thestrength of evidence for or against a specific treatment or procedureand including estimates of expected health outcomes where dataexist In controversial areas or with respect to issues without evi-dence other than usual clinical practice a consensus was achieved byagreement of the expert panel after thorough deliberation
In contrast to guidelines we opted for an easier and user-friendlysystem of ranking using lsquocoloured heartsrsquo that should allow physiciansto easily assess the current status of the evidence and consequent guid-ance (Table 1) This EHRA grading of consensus statements does nothave separate definitions of the level of evidence This categorizationused for consensus statements must not be considered as directlysimilar to that used for official society guideline recommendationswhich apply a classification (Class IndashIII) and level of evidence (A B andC) to recommendations used in official guidelines
Thus a green heart indicates a lsquoshould do thisrsquo consensus statementor indicated treatment or procedure that is based on at least onerandomized trial or is supported by strong observational evidencethat it is beneficial and effective A yellow heart indicates generalagreement andor scientific evidence favouring a lsquomay do thisrsquo state-ment or the usefulnessefficacy of a treatment or procedure A lsquoyellowheartrsquo symbol may be supported by randomized trials based on a smallnumber of patients or which is not widely applicable Treatment strat-egies for which there is scientific evidence of potential harm andshould not be used (lsquodo not do thisrsquo) are indicated by a red heart
Mechanisms and pathophysiologyof cardiac arrhythmias inendocrine disorders
A number of cardiac arrhythmia mechanisms may underlie ventricu-lar and atrial arrhythmias such as reentry abnormal automaticity ortriggered activity Normally these mechanisms are not active in anormal (young) heart The only exceptions are inherited arrhythmiasyndromes in which cardiac remodelling may be present that makethe heart more vulnerable often under specific circumstances likethe excess of catecholamines
Acutely hormones can play a crucial role such as in catecholamine-induced polymorphic VT induced by exercise or in the long QT syn-drome (LQTS) induced either by sleep fear or excitement Often thechallenge provided acutely by these hormones exceeds the safety mar-gins (=reserve) of the vulnerable heart to overcome and ventricular ar-rhythmias ensue Thus endocrine disorders may play an acute role inthe triggering of cardiac arrhythmias (Figure 1)
However there are also chronic adaptations induced by endocrinedisorders that can underlie the formation of arrhythmias The action po-tential is controlled by numerous ion currents that either provides in-ward or outward currents It is this delicate balance that shapes the
2 B Gorenek et al
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action potential and determines its duration often measured as QT-duration Overexpression or down-regulation of these ion currents canchronically increase or decrease conduction or repolarization reserve
A few examples have been listed
Diabetes mellitus In an experimental model mimicking diabetes type 1 itwas demonstrated that this metabolic disorder reduced repolarizationreserve by decreasing the outward current lsquoslowly delayed rectifier (IKs)rsquoin the rabbit thereby increasing the liability for drug induced Torsade dePointes1 More recently it has been suggested that the transcription ofion channels due to the involvement of the P13K pathway is responsiblefor this reduced transcription2
Gender differences The incidence and prevalence of AF and sustained ven-tricular arrhythmias and sudden cardiac death (SCD) are lower in womenthan in men However women have a greater chance to developTorsade de Pointes arrhythmias3 It has been shown that sex hormonesaccount for most of the differences in the cardiac electrophysiologicalproperties observed between females and males Human data demon-strate that the expression of a number of potassium channels is reduced
in females accounting for a prolonged duration of the ventricular actionpotential4 Testosterone reduces the ventricular action potential duration(APD) by enhancing the slow delayed rectifier current and by increasingthe l-type calcium current4
Adrenal dysfunction Glucocorticoid has been reported to be important forthe maintenance of membrane Calcium transport in the cardiac sarcoplas-mic reticulum and for the regulation of various ion channels including IKsand the rapid delayed rectifier (IKr) thereby manipulating QT duration5
Management of arrhythmias inspecific endocrine disorders
Diabetes mellitusDiabetes mellitus (DM) type 1 (reduced insulin production) or type 2(increased resistance to insulin) may increase the risk of cardiac ar-rhythmias via many factors including (i) cardiovascular risk factors (eghypertension) (ii) atherosclerotic cardiovascular disease [ie coronary
Table 1 Scientific rationale of recommendationsa
Definitions where related to a treatment or
procedure
Consensus statement
instruction
Symbol
Scientific evidence that a treatment or procedure is
beneficial and effective Requires at least one
randomized trial or is supported by strong observa-
tional evidence and authorsrsquo consensus (as indicated
by an asterisk)
lsquoShould do thisrsquo
General agreement andor scientific evidence favour
the usefulnessefficacy of a treatment or procedure
May be supported by randomized trials based on a
small number of patients or which is not widely
applicable
lsquoMay do thisrsquo
Scientific evidence or general agreement not to use or
recommend a treatment or procedure
lsquoDo not do thisrsquo
aThis categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply aclassification (IndashIII) and level of evidence (A B and C) to recommendations
Slowed conduction - fibrosis
Neuro hormones = Trigger
Ectopy (non) sustained VT and VF when
conduction andrepolarisation reserve
Intracellular Ca handling ndash prolonged repolarization
Reentry
inherited
disease
Abnormal Automaticity Triggered activity
Figure 1 Mechanism of arrhythmias in endocrine disorders The balance between the strength of the heart to de- or repolarize is often challengedby the autonomic nervous system When the balance is off the heart has to allow arrhythmias which can be based upon numerous arrhythmogenicmechanisms VF ventricular fibrillation VT ventricular tachycardia
EHRA position paper on arrhythmia management in endocrine disorders 3
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artery disease (CAD) prior myocardial infarction (MI) stroke or per-ipheral arterial disease]6ndash8 and (iii) DM-associated factors such as glu-cose control diabetic neuropathy or cardiomyopathy (Figure 2)6910
The risk for arrhythmias or SCD in DM patients is closely related tothe presence and severity of underlying cardiovascular disease611ndash13
but the aforementioned DM-related factors could induce arrhythmiasindependently of cardiovascular comorbidities Management of cardiacarrhythmias in DM patients is outlined in Figure 3
Atrial fibrillationMany epidemiological studies have reported an association of DMwith incident AF1415 The duration of DM and glycaemic control werealso associated with AF (each year with DM conferred a 3 increasein the risk of AF)16 whilst HbA1c of gt9 was associated with a nearlytwo-fold increase in AF risk17 A meta-analysis of 11 studies with atotal of 108 703 AF cases in 1 686 097 subjects showed a 40 greaterrisk of AF in the presence of DM but the effect was attenuated afteradjustment for multiple risk factors [relative risk 124 95 confidenceinterval (CI) 106ndash144] whilst the population-attributable estimatefor AF owing to DM was 25 (95 CI 01ndash39)18 In several observa-tional studies the age-adjusted association of DM with incident AFwas no longer significant after multiple adjustments for hypertensioncardiovascular comorbidity body mass index or obesity19ndash21 thus
suggesting that strategies for AF prevention in DM patients shouldfocus on the control of DM-associated comorbidities (especially theweight and blood pressure control)19
Indeed in the ADVANCE (Action in Diabetes and Vascular DiseasePreterax and Diamicron Modified Release Controlled Evaluation) studyDM patients with AF (76) had significantly greater risks for all-causedeath cardiovascular death major cerebrovascular events and heart fail-ure compared with DM patients without AF Blood pressure loweringyielded similar relative risk reduction in all-cause and cardiovascular mor-tality but owing to their higher risk of these events the absolute benefitsfrom blood pressure control appeared much greater in AF patients22 Inthe VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trialhypertensive patients with new-onset DM had higher rates of new-onsetAF compared with non-DM patients and were at higher risk of heart fail-ure23 Hence AF in DM patients should be viewed as a marker ofadverse outcome which should prompt aggressive management of allconcomitant risk factors (Figure 3)24 Importantly intensive glucose low-ering (target HbA1c lt60) has been associated with similar incident AFrates as a less stringent approach (HbA1c lt80) but with increasedrisk of death and other cardiovascular events17
Since asymptomatic (silent) AF is not uncommon especially inpatients with DM25 at least opportunistic screening for AF with pulsepalpation should be performed in DM patients as also recommended
Hypoglycemia Hyperglycemia HypokalemiaInsulin
reduction
Ischemia Catecholamines Oxidave stress
Alteredintercellular
coupling
Reduced Na+
channel function
Cardiacfibosis
Ca++ handlingabnormalities
K+ channelsdysfunction
downregulation
ABNORMALCONDUCTION
PROLONGEDREPOLARIZATION
- Na+ channel dysfunction- Gap junction uncoupling downup regulation- Reduced gap junction conductivity- Fibrosis
- Impaired APD adaptation- APD alternans- EADs and DADs- Abnormal Ca++ cycling
ARRHYTHMOGENESIS
Diabetic
Cardiom
yopathy
Abnormalionchannelfunction
Electricalremodeling
Autonomicdysregulation
Structuralremodeling
Altered m
olecular signaling
ReentryTriggered
activity
CV riskfactors
atheroscleroticCV disease
Diabetic
Neuropathy
Figure 2 Arrhythmogenesis in diabetes mellitus APD action potential duration CV cardiovascular DADs delayed after depolarizations EADsearly after depolarizations dark blue conditions white disorders yellow pathophysiologic and physiologic pathways dark grey contributing dis-orders and risk factors pink structural cellular and ion channel abnormalities blue mechanisms of arrhythmogenesis red electrophysiologicalabnormalities and arrhythmogenesis
4 B Gorenek et al
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Figure 3 General principles of management of cardiac arrhythmias in patients with diabetes mellitus AADs antiarrhythmic drugs ACEi angioten-sin-converting enzyme inhibitor AFL atrial flutter AHI apnoea-hypopnea index ARB angiotensin receptor blocker AVNRT atrioventricular nodalre-entrant tachycardia AVRT atrioventricular re-entrant tachycardia BMI body mass index BP blood pressure CAD coronary artery diseaseCPAP continuous positive airway pressure CRT cardiac resynchronization therapy CV cardiovascular DM diabetes mellitus ECG electrocardio-gram HT hypertension ICD implantable cardioverter-defibrillator LA left atrium LV left ventricle MRI magnetic resonance imaging NOACsnon-vitamin K antagonist oral anticoagulants OAC oral anticoagulant therapy PM pacemaker SE systemic embolism VKA vitamin K antagonistVPBs ventricular premature beats VT ns ventricular tachycardia non-sustained
EHRA position paper on arrhythmia management in endocrine disorders 5
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Figure 3 Continued
6 B Gorenek et al
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Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
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for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
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Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
and Sociedad Latinoamericana de Estimulacion Cardıaca y Electrofisiologıa (SOLAECE) with the remit of compre-hensively reviewing the available evidence and publishing a joint consensus document on endocrine disorders andcardiac arrhythmias and providing up-to-date consensus recommendations for use in clinical practice
Keywords Endocrine disorders bull Arrhythmias bull Atrial fibrillation bull Ventricular arrhythmias bull Cardiac implantableelectronic device bull Pacemaker bull Implantable cardioverter-defibrillator bull Catheter ablation bull Diabetes
bull Thyroid disorders bull Hyperthyroidism bull Hypothyroidism bull Pheochromocytoma bull Growth hormonedysfunction bull Hyperaldosteronism bull Adrenal insufficiency bull Parathyroid disease bull Stroke bull Oralanticoagulation bull EHRA position paper
Table of Contents
Introduction 2Evidence review 2
Mechanisms and pathophysiology of cardiac arrhythmias in endocrinedisorders 2
Management of arrhythmias in specific endocrine disorders 3Pancreas dysfunction 3
Diabetes mellitus 3Thyroid dysfunction 10
Hyperthyroidism 10Hypothyroidism 11Amiodarone-induced thyroid dysfunction 14
Pheochromocytoma 18Growth hormone dysfunction 19
Acromegaly 19Growth hormone deficiency 19
Diseases of adrenal cortex 20Hyperaldosteronism 21Adrenal insufficiency 20
Parathyroid disease 21Sex hormones-related differences in the risk of arrhythmias 21
Stroke risk assessment and prevention of arrhythmias associated withendocrine disorders 22
Catheter ablation of arrhythmias associated with endocrine disorders 23Device-based therapy of arrhythmias in patients with endocrine
disorders 23Current research gaps ongoing trials and future directions 24
Introduction
However the ultimate judgement on the care of a specific patientmust be made by the healthcare provider and the patient in light of allindividual factors presented
Evidence reviewThis document was prepared by the Task Force with representationfrom EHRA APHRS and SOLAECE and peer-reviewed by official ex-ternal reviewers representing EHRA HRS APHRS and SOLAECETheir members made a detailed literature review weighing thestrength of evidence for or against a specific treatment or procedureand including estimates of expected health outcomes where dataexist In controversial areas or with respect to issues without evi-dence other than usual clinical practice a consensus was achieved byagreement of the expert panel after thorough deliberation
In contrast to guidelines we opted for an easier and user-friendlysystem of ranking using lsquocoloured heartsrsquo that should allow physiciansto easily assess the current status of the evidence and consequent guid-ance (Table 1) This EHRA grading of consensus statements does nothave separate definitions of the level of evidence This categorizationused for consensus statements must not be considered as directlysimilar to that used for official society guideline recommendationswhich apply a classification (Class IndashIII) and level of evidence (A B andC) to recommendations used in official guidelines
Thus a green heart indicates a lsquoshould do thisrsquo consensus statementor indicated treatment or procedure that is based on at least onerandomized trial or is supported by strong observational evidencethat it is beneficial and effective A yellow heart indicates generalagreement andor scientific evidence favouring a lsquomay do thisrsquo state-ment or the usefulnessefficacy of a treatment or procedure A lsquoyellowheartrsquo symbol may be supported by randomized trials based on a smallnumber of patients or which is not widely applicable Treatment strat-egies for which there is scientific evidence of potential harm andshould not be used (lsquodo not do thisrsquo) are indicated by a red heart
Mechanisms and pathophysiologyof cardiac arrhythmias inendocrine disorders
A number of cardiac arrhythmia mechanisms may underlie ventricu-lar and atrial arrhythmias such as reentry abnormal automaticity ortriggered activity Normally these mechanisms are not active in anormal (young) heart The only exceptions are inherited arrhythmiasyndromes in which cardiac remodelling may be present that makethe heart more vulnerable often under specific circumstances likethe excess of catecholamines
Acutely hormones can play a crucial role such as in catecholamine-induced polymorphic VT induced by exercise or in the long QT syn-drome (LQTS) induced either by sleep fear or excitement Often thechallenge provided acutely by these hormones exceeds the safety mar-gins (=reserve) of the vulnerable heart to overcome and ventricular ar-rhythmias ensue Thus endocrine disorders may play an acute role inthe triggering of cardiac arrhythmias (Figure 1)
However there are also chronic adaptations induced by endocrinedisorders that can underlie the formation of arrhythmias The action po-tential is controlled by numerous ion currents that either provides in-ward or outward currents It is this delicate balance that shapes the
2 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
action potential and determines its duration often measured as QT-duration Overexpression or down-regulation of these ion currents canchronically increase or decrease conduction or repolarization reserve
A few examples have been listed
Diabetes mellitus In an experimental model mimicking diabetes type 1 itwas demonstrated that this metabolic disorder reduced repolarizationreserve by decreasing the outward current lsquoslowly delayed rectifier (IKs)rsquoin the rabbit thereby increasing the liability for drug induced Torsade dePointes1 More recently it has been suggested that the transcription ofion channels due to the involvement of the P13K pathway is responsiblefor this reduced transcription2
Gender differences The incidence and prevalence of AF and sustained ven-tricular arrhythmias and sudden cardiac death (SCD) are lower in womenthan in men However women have a greater chance to developTorsade de Pointes arrhythmias3 It has been shown that sex hormonesaccount for most of the differences in the cardiac electrophysiologicalproperties observed between females and males Human data demon-strate that the expression of a number of potassium channels is reduced
in females accounting for a prolonged duration of the ventricular actionpotential4 Testosterone reduces the ventricular action potential duration(APD) by enhancing the slow delayed rectifier current and by increasingthe l-type calcium current4
Adrenal dysfunction Glucocorticoid has been reported to be important forthe maintenance of membrane Calcium transport in the cardiac sarcoplas-mic reticulum and for the regulation of various ion channels including IKsand the rapid delayed rectifier (IKr) thereby manipulating QT duration5
Management of arrhythmias inspecific endocrine disorders
Diabetes mellitusDiabetes mellitus (DM) type 1 (reduced insulin production) or type 2(increased resistance to insulin) may increase the risk of cardiac ar-rhythmias via many factors including (i) cardiovascular risk factors (eghypertension) (ii) atherosclerotic cardiovascular disease [ie coronary
Table 1 Scientific rationale of recommendationsa
Definitions where related to a treatment or
procedure
Consensus statement
instruction
Symbol
Scientific evidence that a treatment or procedure is
beneficial and effective Requires at least one
randomized trial or is supported by strong observa-
tional evidence and authorsrsquo consensus (as indicated
by an asterisk)
lsquoShould do thisrsquo
General agreement andor scientific evidence favour
the usefulnessefficacy of a treatment or procedure
May be supported by randomized trials based on a
small number of patients or which is not widely
applicable
lsquoMay do thisrsquo
Scientific evidence or general agreement not to use or
recommend a treatment or procedure
lsquoDo not do thisrsquo
aThis categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply aclassification (IndashIII) and level of evidence (A B and C) to recommendations
Slowed conduction - fibrosis
Neuro hormones = Trigger
Ectopy (non) sustained VT and VF when
conduction andrepolarisation reserve
Intracellular Ca handling ndash prolonged repolarization
Reentry
inherited
disease
Abnormal Automaticity Triggered activity
Figure 1 Mechanism of arrhythmias in endocrine disorders The balance between the strength of the heart to de- or repolarize is often challengedby the autonomic nervous system When the balance is off the heart has to allow arrhythmias which can be based upon numerous arrhythmogenicmechanisms VF ventricular fibrillation VT ventricular tachycardia
EHRA position paper on arrhythmia management in endocrine disorders 3
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artery disease (CAD) prior myocardial infarction (MI) stroke or per-ipheral arterial disease]6ndash8 and (iii) DM-associated factors such as glu-cose control diabetic neuropathy or cardiomyopathy (Figure 2)6910
The risk for arrhythmias or SCD in DM patients is closely related tothe presence and severity of underlying cardiovascular disease611ndash13
but the aforementioned DM-related factors could induce arrhythmiasindependently of cardiovascular comorbidities Management of cardiacarrhythmias in DM patients is outlined in Figure 3
Atrial fibrillationMany epidemiological studies have reported an association of DMwith incident AF1415 The duration of DM and glycaemic control werealso associated with AF (each year with DM conferred a 3 increasein the risk of AF)16 whilst HbA1c of gt9 was associated with a nearlytwo-fold increase in AF risk17 A meta-analysis of 11 studies with atotal of 108 703 AF cases in 1 686 097 subjects showed a 40 greaterrisk of AF in the presence of DM but the effect was attenuated afteradjustment for multiple risk factors [relative risk 124 95 confidenceinterval (CI) 106ndash144] whilst the population-attributable estimatefor AF owing to DM was 25 (95 CI 01ndash39)18 In several observa-tional studies the age-adjusted association of DM with incident AFwas no longer significant after multiple adjustments for hypertensioncardiovascular comorbidity body mass index or obesity19ndash21 thus
suggesting that strategies for AF prevention in DM patients shouldfocus on the control of DM-associated comorbidities (especially theweight and blood pressure control)19
Indeed in the ADVANCE (Action in Diabetes and Vascular DiseasePreterax and Diamicron Modified Release Controlled Evaluation) studyDM patients with AF (76) had significantly greater risks for all-causedeath cardiovascular death major cerebrovascular events and heart fail-ure compared with DM patients without AF Blood pressure loweringyielded similar relative risk reduction in all-cause and cardiovascular mor-tality but owing to their higher risk of these events the absolute benefitsfrom blood pressure control appeared much greater in AF patients22 Inthe VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trialhypertensive patients with new-onset DM had higher rates of new-onsetAF compared with non-DM patients and were at higher risk of heart fail-ure23 Hence AF in DM patients should be viewed as a marker ofadverse outcome which should prompt aggressive management of allconcomitant risk factors (Figure 3)24 Importantly intensive glucose low-ering (target HbA1c lt60) has been associated with similar incident AFrates as a less stringent approach (HbA1c lt80) but with increasedrisk of death and other cardiovascular events17
Since asymptomatic (silent) AF is not uncommon especially inpatients with DM25 at least opportunistic screening for AF with pulsepalpation should be performed in DM patients as also recommended
Hypoglycemia Hyperglycemia HypokalemiaInsulin
reduction
Ischemia Catecholamines Oxidave stress
Alteredintercellular
coupling
Reduced Na+
channel function
Cardiacfibosis
Ca++ handlingabnormalities
K+ channelsdysfunction
downregulation
ABNORMALCONDUCTION
PROLONGEDREPOLARIZATION
- Na+ channel dysfunction- Gap junction uncoupling downup regulation- Reduced gap junction conductivity- Fibrosis
- Impaired APD adaptation- APD alternans- EADs and DADs- Abnormal Ca++ cycling
ARRHYTHMOGENESIS
Diabetic
Cardiom
yopathy
Abnormalionchannelfunction
Electricalremodeling
Autonomicdysregulation
Structuralremodeling
Altered m
olecular signaling
ReentryTriggered
activity
CV riskfactors
atheroscleroticCV disease
Diabetic
Neuropathy
Figure 2 Arrhythmogenesis in diabetes mellitus APD action potential duration CV cardiovascular DADs delayed after depolarizations EADsearly after depolarizations dark blue conditions white disorders yellow pathophysiologic and physiologic pathways dark grey contributing dis-orders and risk factors pink structural cellular and ion channel abnormalities blue mechanisms of arrhythmogenesis red electrophysiologicalabnormalities and arrhythmogenesis
4 B Gorenek et al
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Figure 3 General principles of management of cardiac arrhythmias in patients with diabetes mellitus AADs antiarrhythmic drugs ACEi angioten-sin-converting enzyme inhibitor AFL atrial flutter AHI apnoea-hypopnea index ARB angiotensin receptor blocker AVNRT atrioventricular nodalre-entrant tachycardia AVRT atrioventricular re-entrant tachycardia BMI body mass index BP blood pressure CAD coronary artery diseaseCPAP continuous positive airway pressure CRT cardiac resynchronization therapy CV cardiovascular DM diabetes mellitus ECG electrocardio-gram HT hypertension ICD implantable cardioverter-defibrillator LA left atrium LV left ventricle MRI magnetic resonance imaging NOACsnon-vitamin K antagonist oral anticoagulants OAC oral anticoagulant therapy PM pacemaker SE systemic embolism VKA vitamin K antagonistVPBs ventricular premature beats VT ns ventricular tachycardia non-sustained
EHRA position paper on arrhythmia management in endocrine disorders 5
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Figure 3 Continued
6 B Gorenek et al
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Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
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for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
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Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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action potential and determines its duration often measured as QT-duration Overexpression or down-regulation of these ion currents canchronically increase or decrease conduction or repolarization reserve
A few examples have been listed
Diabetes mellitus In an experimental model mimicking diabetes type 1 itwas demonstrated that this metabolic disorder reduced repolarizationreserve by decreasing the outward current lsquoslowly delayed rectifier (IKs)rsquoin the rabbit thereby increasing the liability for drug induced Torsade dePointes1 More recently it has been suggested that the transcription ofion channels due to the involvement of the P13K pathway is responsiblefor this reduced transcription2
Gender differences The incidence and prevalence of AF and sustained ven-tricular arrhythmias and sudden cardiac death (SCD) are lower in womenthan in men However women have a greater chance to developTorsade de Pointes arrhythmias3 It has been shown that sex hormonesaccount for most of the differences in the cardiac electrophysiologicalproperties observed between females and males Human data demon-strate that the expression of a number of potassium channels is reduced
in females accounting for a prolonged duration of the ventricular actionpotential4 Testosterone reduces the ventricular action potential duration(APD) by enhancing the slow delayed rectifier current and by increasingthe l-type calcium current4
Adrenal dysfunction Glucocorticoid has been reported to be important forthe maintenance of membrane Calcium transport in the cardiac sarcoplas-mic reticulum and for the regulation of various ion channels including IKsand the rapid delayed rectifier (IKr) thereby manipulating QT duration5
Management of arrhythmias inspecific endocrine disorders
Diabetes mellitusDiabetes mellitus (DM) type 1 (reduced insulin production) or type 2(increased resistance to insulin) may increase the risk of cardiac ar-rhythmias via many factors including (i) cardiovascular risk factors (eghypertension) (ii) atherosclerotic cardiovascular disease [ie coronary
Table 1 Scientific rationale of recommendationsa
Definitions where related to a treatment or
procedure
Consensus statement
instruction
Symbol
Scientific evidence that a treatment or procedure is
beneficial and effective Requires at least one
randomized trial or is supported by strong observa-
tional evidence and authorsrsquo consensus (as indicated
by an asterisk)
lsquoShould do thisrsquo
General agreement andor scientific evidence favour
the usefulnessefficacy of a treatment or procedure
May be supported by randomized trials based on a
small number of patients or which is not widely
applicable
lsquoMay do thisrsquo
Scientific evidence or general agreement not to use or
recommend a treatment or procedure
lsquoDo not do thisrsquo
aThis categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply aclassification (IndashIII) and level of evidence (A B and C) to recommendations
Slowed conduction - fibrosis
Neuro hormones = Trigger
Ectopy (non) sustained VT and VF when
conduction andrepolarisation reserve
Intracellular Ca handling ndash prolonged repolarization
Reentry
inherited
disease
Abnormal Automaticity Triggered activity
Figure 1 Mechanism of arrhythmias in endocrine disorders The balance between the strength of the heart to de- or repolarize is often challengedby the autonomic nervous system When the balance is off the heart has to allow arrhythmias which can be based upon numerous arrhythmogenicmechanisms VF ventricular fibrillation VT ventricular tachycardia
EHRA position paper on arrhythmia management in endocrine disorders 3
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artery disease (CAD) prior myocardial infarction (MI) stroke or per-ipheral arterial disease]6ndash8 and (iii) DM-associated factors such as glu-cose control diabetic neuropathy or cardiomyopathy (Figure 2)6910
The risk for arrhythmias or SCD in DM patients is closely related tothe presence and severity of underlying cardiovascular disease611ndash13
but the aforementioned DM-related factors could induce arrhythmiasindependently of cardiovascular comorbidities Management of cardiacarrhythmias in DM patients is outlined in Figure 3
Atrial fibrillationMany epidemiological studies have reported an association of DMwith incident AF1415 The duration of DM and glycaemic control werealso associated with AF (each year with DM conferred a 3 increasein the risk of AF)16 whilst HbA1c of gt9 was associated with a nearlytwo-fold increase in AF risk17 A meta-analysis of 11 studies with atotal of 108 703 AF cases in 1 686 097 subjects showed a 40 greaterrisk of AF in the presence of DM but the effect was attenuated afteradjustment for multiple risk factors [relative risk 124 95 confidenceinterval (CI) 106ndash144] whilst the population-attributable estimatefor AF owing to DM was 25 (95 CI 01ndash39)18 In several observa-tional studies the age-adjusted association of DM with incident AFwas no longer significant after multiple adjustments for hypertensioncardiovascular comorbidity body mass index or obesity19ndash21 thus
suggesting that strategies for AF prevention in DM patients shouldfocus on the control of DM-associated comorbidities (especially theweight and blood pressure control)19
Indeed in the ADVANCE (Action in Diabetes and Vascular DiseasePreterax and Diamicron Modified Release Controlled Evaluation) studyDM patients with AF (76) had significantly greater risks for all-causedeath cardiovascular death major cerebrovascular events and heart fail-ure compared with DM patients without AF Blood pressure loweringyielded similar relative risk reduction in all-cause and cardiovascular mor-tality but owing to their higher risk of these events the absolute benefitsfrom blood pressure control appeared much greater in AF patients22 Inthe VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trialhypertensive patients with new-onset DM had higher rates of new-onsetAF compared with non-DM patients and were at higher risk of heart fail-ure23 Hence AF in DM patients should be viewed as a marker ofadverse outcome which should prompt aggressive management of allconcomitant risk factors (Figure 3)24 Importantly intensive glucose low-ering (target HbA1c lt60) has been associated with similar incident AFrates as a less stringent approach (HbA1c lt80) but with increasedrisk of death and other cardiovascular events17
Since asymptomatic (silent) AF is not uncommon especially inpatients with DM25 at least opportunistic screening for AF with pulsepalpation should be performed in DM patients as also recommended
Hypoglycemia Hyperglycemia HypokalemiaInsulin
reduction
Ischemia Catecholamines Oxidave stress
Alteredintercellular
coupling
Reduced Na+
channel function
Cardiacfibosis
Ca++ handlingabnormalities
K+ channelsdysfunction
downregulation
ABNORMALCONDUCTION
PROLONGEDREPOLARIZATION
- Na+ channel dysfunction- Gap junction uncoupling downup regulation- Reduced gap junction conductivity- Fibrosis
- Impaired APD adaptation- APD alternans- EADs and DADs- Abnormal Ca++ cycling
ARRHYTHMOGENESIS
Diabetic
Cardiom
yopathy
Abnormalionchannelfunction
Electricalremodeling
Autonomicdysregulation
Structuralremodeling
Altered m
olecular signaling
ReentryTriggered
activity
CV riskfactors
atheroscleroticCV disease
Diabetic
Neuropathy
Figure 2 Arrhythmogenesis in diabetes mellitus APD action potential duration CV cardiovascular DADs delayed after depolarizations EADsearly after depolarizations dark blue conditions white disorders yellow pathophysiologic and physiologic pathways dark grey contributing dis-orders and risk factors pink structural cellular and ion channel abnormalities blue mechanisms of arrhythmogenesis red electrophysiologicalabnormalities and arrhythmogenesis
4 B Gorenek et al
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Figure 3 General principles of management of cardiac arrhythmias in patients with diabetes mellitus AADs antiarrhythmic drugs ACEi angioten-sin-converting enzyme inhibitor AFL atrial flutter AHI apnoea-hypopnea index ARB angiotensin receptor blocker AVNRT atrioventricular nodalre-entrant tachycardia AVRT atrioventricular re-entrant tachycardia BMI body mass index BP blood pressure CAD coronary artery diseaseCPAP continuous positive airway pressure CRT cardiac resynchronization therapy CV cardiovascular DM diabetes mellitus ECG electrocardio-gram HT hypertension ICD implantable cardioverter-defibrillator LA left atrium LV left ventricle MRI magnetic resonance imaging NOACsnon-vitamin K antagonist oral anticoagulants OAC oral anticoagulant therapy PM pacemaker SE systemic embolism VKA vitamin K antagonistVPBs ventricular premature beats VT ns ventricular tachycardia non-sustained
EHRA position paper on arrhythmia management in endocrine disorders 5
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Figure 3 Continued
6 B Gorenek et al
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Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
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for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
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Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
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23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
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28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
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39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
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44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
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46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
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95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
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98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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artery disease (CAD) prior myocardial infarction (MI) stroke or per-ipheral arterial disease]6ndash8 and (iii) DM-associated factors such as glu-cose control diabetic neuropathy or cardiomyopathy (Figure 2)6910
The risk for arrhythmias or SCD in DM patients is closely related tothe presence and severity of underlying cardiovascular disease611ndash13
but the aforementioned DM-related factors could induce arrhythmiasindependently of cardiovascular comorbidities Management of cardiacarrhythmias in DM patients is outlined in Figure 3
Atrial fibrillationMany epidemiological studies have reported an association of DMwith incident AF1415 The duration of DM and glycaemic control werealso associated with AF (each year with DM conferred a 3 increasein the risk of AF)16 whilst HbA1c of gt9 was associated with a nearlytwo-fold increase in AF risk17 A meta-analysis of 11 studies with atotal of 108 703 AF cases in 1 686 097 subjects showed a 40 greaterrisk of AF in the presence of DM but the effect was attenuated afteradjustment for multiple risk factors [relative risk 124 95 confidenceinterval (CI) 106ndash144] whilst the population-attributable estimatefor AF owing to DM was 25 (95 CI 01ndash39)18 In several observa-tional studies the age-adjusted association of DM with incident AFwas no longer significant after multiple adjustments for hypertensioncardiovascular comorbidity body mass index or obesity19ndash21 thus
suggesting that strategies for AF prevention in DM patients shouldfocus on the control of DM-associated comorbidities (especially theweight and blood pressure control)19
Indeed in the ADVANCE (Action in Diabetes and Vascular DiseasePreterax and Diamicron Modified Release Controlled Evaluation) studyDM patients with AF (76) had significantly greater risks for all-causedeath cardiovascular death major cerebrovascular events and heart fail-ure compared with DM patients without AF Blood pressure loweringyielded similar relative risk reduction in all-cause and cardiovascular mor-tality but owing to their higher risk of these events the absolute benefitsfrom blood pressure control appeared much greater in AF patients22 Inthe VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trialhypertensive patients with new-onset DM had higher rates of new-onsetAF compared with non-DM patients and were at higher risk of heart fail-ure23 Hence AF in DM patients should be viewed as a marker ofadverse outcome which should prompt aggressive management of allconcomitant risk factors (Figure 3)24 Importantly intensive glucose low-ering (target HbA1c lt60) has been associated with similar incident AFrates as a less stringent approach (HbA1c lt80) but with increasedrisk of death and other cardiovascular events17
Since asymptomatic (silent) AF is not uncommon especially inpatients with DM25 at least opportunistic screening for AF with pulsepalpation should be performed in DM patients as also recommended
Hypoglycemia Hyperglycemia HypokalemiaInsulin
reduction
Ischemia Catecholamines Oxidave stress
Alteredintercellular
coupling
Reduced Na+
channel function
Cardiacfibosis
Ca++ handlingabnormalities
K+ channelsdysfunction
downregulation
ABNORMALCONDUCTION
PROLONGEDREPOLARIZATION
- Na+ channel dysfunction- Gap junction uncoupling downup regulation- Reduced gap junction conductivity- Fibrosis
- Impaired APD adaptation- APD alternans- EADs and DADs- Abnormal Ca++ cycling
ARRHYTHMOGENESIS
Diabetic
Cardiom
yopathy
Abnormalionchannelfunction
Electricalremodeling
Autonomicdysregulation
Structuralremodeling
Altered m
olecular signaling
ReentryTriggered
activity
CV riskfactors
atheroscleroticCV disease
Diabetic
Neuropathy
Figure 2 Arrhythmogenesis in diabetes mellitus APD action potential duration CV cardiovascular DADs delayed after depolarizations EADsearly after depolarizations dark blue conditions white disorders yellow pathophysiologic and physiologic pathways dark grey contributing dis-orders and risk factors pink structural cellular and ion channel abnormalities blue mechanisms of arrhythmogenesis red electrophysiologicalabnormalities and arrhythmogenesis
4 B Gorenek et al
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Figure 3 General principles of management of cardiac arrhythmias in patients with diabetes mellitus AADs antiarrhythmic drugs ACEi angioten-sin-converting enzyme inhibitor AFL atrial flutter AHI apnoea-hypopnea index ARB angiotensin receptor blocker AVNRT atrioventricular nodalre-entrant tachycardia AVRT atrioventricular re-entrant tachycardia BMI body mass index BP blood pressure CAD coronary artery diseaseCPAP continuous positive airway pressure CRT cardiac resynchronization therapy CV cardiovascular DM diabetes mellitus ECG electrocardio-gram HT hypertension ICD implantable cardioverter-defibrillator LA left atrium LV left ventricle MRI magnetic resonance imaging NOACsnon-vitamin K antagonist oral anticoagulants OAC oral anticoagulant therapy PM pacemaker SE systemic embolism VKA vitamin K antagonistVPBs ventricular premature beats VT ns ventricular tachycardia non-sustained
EHRA position paper on arrhythmia management in endocrine disorders 5
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Figure 3 Continued
6 B Gorenek et al
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Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
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for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
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Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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Figure 3 General principles of management of cardiac arrhythmias in patients with diabetes mellitus AADs antiarrhythmic drugs ACEi angioten-sin-converting enzyme inhibitor AFL atrial flutter AHI apnoea-hypopnea index ARB angiotensin receptor blocker AVNRT atrioventricular nodalre-entrant tachycardia AVRT atrioventricular re-entrant tachycardia BMI body mass index BP blood pressure CAD coronary artery diseaseCPAP continuous positive airway pressure CRT cardiac resynchronization therapy CV cardiovascular DM diabetes mellitus ECG electrocardio-gram HT hypertension ICD implantable cardioverter-defibrillator LA left atrium LV left ventricle MRI magnetic resonance imaging NOACsnon-vitamin K antagonist oral anticoagulants OAC oral anticoagulant therapy PM pacemaker SE systemic embolism VKA vitamin K antagonistVPBs ventricular premature beats VT ns ventricular tachycardia non-sustained
EHRA position paper on arrhythmia management in endocrine disorders 5
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Figure 3 Continued
6 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
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Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Figure 3 Continued
6 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
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Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
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Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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Table 2 Randomized controlled trials of intensive vs standard glycaemic control in adult patients with diabetesmellitus
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
ADVANCE72
2008
11 140
DM type 2
Gliclazide HbA1c lt_65 Median 5 years Microvascular events
94 vs 109
HR 086 (077ndash097) P = 001
Macrovascular events
100 vs 106
HR 094 (084ndash106) P = 032
Cardiovascular death
45 vs 52
HR 088 (074ndash104) P = 012
All-cause death
89 vs 96
HR 093 (083ndash106) P = 028
27 vs 15
HR 186 (142ndash240)
P lt 0001
ACCORD54 2008
ACCORD53 2011
10 251
DM Type 2
known CV dis-
ease or CV risk
factors
Various
The intensive
regimen
stopped
early due to
increased
mortality
HbA1c lt60 Mean 35 years All-cause death
141 vs 114
HR 122 (101ndash146) P = 004
Cardiovascular death
26 vs 18
HR 135 (104ndash176) P = 002
Fatal arrhythmia
01 vs 02
Primary outcome (composite of
non-fatal MI stroke or CV
death)
69 vs 72
HR 090 (078ndash104) P = 016
At 5-year follow-up the
rates of non-fatal MI were
lower [118 vs 142 HR
082 (070ndash096) P = 001]
but the rates of CV death
(072 vs 057 HR 129
(104ndash160) P = 002) and
all-cause death [153 vs
127 HR 119 (103ndash138)
P = 002] were higher with
intensive glucose control
Fatal arrhythmia
01 vs 04
31 vs 10
P lt 0001
VADT73 2009 1791 military vet-
erans DM Type
2 40 with pre-
vious CV event
Various
Open-label
study
An absolute
reduction for
15 points in
HbA1c com-
pared with
standard glu-
cose control
Median 56 years 6-year event free rates stand-
ard vs intensive control
Cardiovascular death
096 vs 095
HR 132 (081ndash214) P = 026
All-cause death
088 vs 087
HR 107 (081ndash142) P = 062
Time to first occurrence of a CV
event
HR 088 (074ndash105) P = 014
212 vs 99
P lt 0001
Continued
EHRA position paper on arrhythmia management in endocrine disorders 7
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
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to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
for all individuals aged gt_65 years26 High-risk DM patients would likelybenefit from an active screening for AF but more data are needed todefine optimal AF screening strategy(ies) in DM patients27 Beforetreatment initiation the presence of AF should be documented usinga 12-lead electrocardiogram (ECG)2628 In DM patients with estab-lished AF ventricular rate control is recommended to decrease symp-toms and prevent AF-related complications In patients withpersistent symptoms despite adequate rate control or in those withleft ventricular dysfunction attributable to poorly controlled high ven-tricular rate or as per patientrsquos preference rhythm control strategycould be attempted29 including catheter ablation30ndash32 or cardiover-sion Of note DM has been associated with increased AF recurrencepost successful cardioversion of persistent AF33 For AF-relatedstroke risk management see Stroke risk assessment and prevention inarrhythmias associated with endocrine disorders
Ventricular arrhythmias and sudden cardiac deathCompared with the general population DM patients have an increasedrisk of both SCD1332ndash35 and non-SCD36 In a meta-analysis of 14 studiesinvolving 346 356 participants and 5647 SCD cases the risk of SCD was
two-fold higher in patients with DM compared with non-DM patients[adjusted hazard ratio (HR) 225 95 CI 17ndash297]29 However DMpatients were also shown to be at nearly three-fold greater risk of non-SCD than non-DM patients (adjusted HR 290 95 CI 189ndash446)36
Observational studies reported marked QTc prolongation37 atypicalmicrovolt T-wave alternans patterns38 altered heart rate variability39ndash43
or heart rate turbulence44ndash46 in DM patients but none of these testshave been routinely used to stratify the risk for ventricular arrhythmiasor SCD in clinical practice47 Both hyper- and hypoglycaemia have beenindependently associated with increased risk of ventricular arrhythmias48
Insulin-induced hypoglycaemia has been associated with nocturnal death(so-called lsquodead-in-bed syndromersquo) in DM type 14950 and arrhythmicdeaths were reported in several DM type 2 trials51ndash54 (Table 2)
There is no DM-specific protocol of screening for SCD47 but asshown in Figure 3 all patients diagnosed with DM should undergo regu-lar screening for cardiovascular risk factors or structural heart diseaseand glycaemic targets should be set individually Patients with DMand symptoms suggestive of cardiac arrhythmias (eg palpitations pre-syncope or syncope) should undergo further detailed diagnostic assess-ment as shown in Figure 3
Table 2 Continued
Study year Cohort size Drug Intensive
glucose
control
Follow-up Study outcomes
(intensive vs standard
glucose control)
Significant
hypoglycaemia
NICE-SUGAR74
2009
NICE-SUGAR51
2012
6104 critically ill
patients
Insulin Blood glucose
45ndash60 mmoll
90 days 90-Day all-cause mortality
275 vs 249
OR 114 (102ndash128) P = 002
Both moderate and severe
hypoglycaemia are associ-
ated with increased risk of
death
285 vs 235 HR 141
(121ndash162) P lt 0001
(moderate hypoglycaemia)
354 vs 235 HR 210
(159ndash277) P lt 0001
(severe hypoglycaemia)
68 vs 05
OR 147 (90ndash259)
P lt 0001
Moderate hypoglycae-
mia n = 2714
(450)
Severe hypoglycaemia
n = 223 (37)
ORIGIN52 2013 12 537
DM Type 2 with
additional CV
risk factors
Insulin glargine Normal glycaemia Median 62 years Severe hypoglycaemia vs others
Composite of CV deathMI or
stroke
HR 158 (124ndash202)
P lt 0001
All-cause mortality
HR 174 (139ndash219)
P lt 0001
CV mortality
HR 171 (127ndash230)
P lt 0001
Arrhythmic death
HR 177 (117ndash267) P = 007
Annual rates of severe
hypoglycaemia
09 vs 03
ACCORD The Action to Control Cardiovascular Risk in Diabetes trial ADVANCE The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified ReleaseControlled Evaluation trial CV cardiovascular DM diabetes mellitus HR hazard ratio MI myocardial infarction NICE-SUGAR The Normoglycaemia in Intensive CareEvaluationmdashSurvival Using Glucose Algorithm Regulation trial OR odds ratio ORIGIN Outcomes Reduction with an Initial Glargine Intervention VADT Veterans AffairsDiabetes Trial
8 B Gorenek et al
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Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Hypoglycaemia-associated arrhythmias are difficult to documentbut observational studies using continuous glucose monitoring(CGM) and Holter monitoring in small DM type 2 cohorts (n = 25)showed that hypoglycaemic episodes were common often asympto-matic and associated with various arrhythmias5556 Compared withdaytime hypoglycaemia nocturnal episodes were more common andassociated with greater risk for bradycardia or atrial ectopy whilstventricular arrhythmias were equally common55 In contrast to ani-mal studies57 in a recent retrospective analysis of the ACCORD(Action to Control Cardiovascular Risk in Diabetes) trial the use ofbeta-blockers in DM patients was associated with increased risk ofsevere hypoglycaemia and cardiovascular events58 but more evi-dence is needed to inform optimal use of beta-blockers in DMpatients without established CAD59 Otherwise the use of antiar-rhythmic drugs should follow the general principles and precautionsrelated to pharmacological treatment of cardiac arrhythmias2647
In high-risk patients with established cardiovascular disease andorlong-standing sub-optimally controlled DM type 2 a less stringent gly-caemic control (ie a target HbA1c of lt_8) is recommended60 sinceintensive glycaemic control has been associated with increased risk ofsevere hypoglycaemic episodes counterbalanced by significant reduc-tion only in microvascular but not macrovascular complications (egMI stroke and mortality) The addition of empagliflozine61 or liraglu-tide62 to standard care should be considered in order to reduce
cardiovascular and all-cause mortality or hospitalization for heartfailure63 In addition the LEADER (Liraglutide Effect and Action inDiabetes Evaluation of Cardiovascular Outcome Results) trial datasuggested that liraglutide may have a renal protective effect6264
Although cardiac arrhythmias were not specifically investigated ineither LEADER or EMPA-REG OUTCOME (EmpagliflozineCardiovascular Outcome Event Trial in Type 2 Diabetes MellitusPatients)60 trial an antiarrhythmic effect of these drugs (perhapsmediated via glucagon release stimulation) has been hypothesized tocontribute to the reduced risk for cardiovascular death6162
The CANVAS Program data showed that the use of anothersodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozinwas associated with significantly lower risk of cardiovascular eventsand a renal protective effect compared with placebo in patients withDM type 2 and an elevated risk of cardiovascular disease65 The inci-dence of cardiovascular events with dapagliflozine is currently investi-gated in the DECLARE-TIMI 58 trial66 and a meta-analysis of 21 trialswith this drug67 suggested the potential for a beneficial cardiovasculareffect consistent with the multifactorial benefits on cardiovascularrisk factors associated with other SGLT2 inhibitors6869 Concerningthe cardiovascular effects of the SGLT1 inhibitors other than liraglu-tide (ie exenatide and lixisenatide) there was no significant differ-ence in the rates of cardiovascular events with these agentscompared with placebo in the respective trial7071
Consensus statements Consensus
statement
instruction
Level of
evidence
References
Diagnostic assessment of patients with DM type 1 and type 2 requires aggressive screening for and a
detailed characterization of underlying cardiovascular risk factors atherosclerotic cardiovascular dis-
ease and DM-related factors (ie glucose regulation diabetic neuropathy and cardiomyopathy) all of
which may increase the risk of cardiac arrhythmias and SCD in DM patients
lsquoShould do thisrsquo 6
Glycaemic targets in patients with DM and cardiac arrhythmias should be defined individually taking into
account patient age individual risk profile life expectancy and patient values and preferences
lsquoShould do thisrsquo 60
Severe hypoglycaemia should be avoided in DM patients at risk of cardiac arrhythmias owing to
increased risk of malignant potentially lethal ventricular arrhythmias and all-cause death
lsquoShould do thisrsquo 60
Intensive glucose control with target HbA1c of lt70 (or even lt60) should not be attempted in eld-
erly andor high-risk DM patients owing to increased risk of severe hypoglycaemia and neutral (or
negative effect) on all-cause mortality
lsquoDo not do thisrsquo 60
Intense management of cardiovascular risk factors (eg obesity dyslipidaemia hypertension obstructive
sleep apnoea etc) in DM patients reduces the risk of cardiac arrhythmias (eg AF) by preventing (or
slowing) the development of atherosclerotic cardiovascular disease and arrhythmogenic substrate
lsquoShould do thisrsquo 26
Incident AF in DM patients should be viewed as a marker of increased risk of adverse cardiovascular
events and mortality Intensive glucose control does not reduce the risk of AF but aggressive manage-
ment of cardiovascular risk factors may delay or prevent AF
lsquoShould do thisrsquo 26
Screening for silent AF by pulse palpation (with ECG confirmation) should be performed in all DM
patients at each regular visit
lsquoShould do thisrsquo 2627
The use of (non-selective) beta-blockers in DM patients without established CAD may be weighed
against the risk of severe hypoglycaemia
lsquoMay do thisrsquo 5859
EHRA position paper on arrhythmia management in endocrine disorders 9
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Thyroid dysfunctionThyroid dysfunction is associated with atrial and ventricular tachyar-rhythmias as well as bradyarrhythmias Hyperthyroidism is accompa-nied by increased automaticity and triggered activity in the atria andpulmonary veins (PVs) while in hypothyroidism effective refractoryperiods of the atria atrioventricular (AV) node bypass tracts andHis-Purkinje system are prolonged75ndash77 Genetic mechanisms involv-ing ion channels and autoimmune mechanisms involving muscarinicand beta-adrenoreceptors that are also linked to long-QT syndromemay contribute to ventricular and atrial arrhythmias in thyroid dys-function7879 Tachy- and bradyarrhythmia occurrence is different inhyperthyroidism and hypothyroidism and the evidence on treatmentis limited (Table 3ndash5)
Hyperthyroidism
Hyperthyroidism overt or subclinical [ie reduced serum thyroidstimulating hormone (TSH) concentration but free thyroxine levelswithin reference ranges] (Table 3) is associated with increased risk ofAF80ndash90 before and after establishment of the diagnosis it is associ-ated with increased risk of cardiovascular disease development91
Hypothyroidism either overt or subclinical has been shown by sev-eral studies confer no AF risk808990 though lack of association is notwell-established92ndash97
Atrial fibrillationAntithyroid treatment and attainment of euthyroid state should bethe first line in management of AF in the setting of hyperthyroidism asin most cases AF reverses spontaneously to sinus rhythm once euthy-roid state is achieved usually after 13ndash15 weeks of therapy98ndash101
Treatment using antithyriod agents radioiodine therapy or thyroidec-tomy is accompanied by conversion to sinus rhythm in 75ndash100 ofcases but predictors of persistent arrhythmia are increased age lon-ger pre-treatment duration of AF and hyperthyroidism99100 For ratecontrol of AF and as an adjunct to antithyriod therapy non-selectivebeta-blockers like propranolol may be used as they exert not onlyantisympathetic effects slowing heart rate but also reduce metabolicrate and affect triiodthyronine levels in case of low-output heart
failure they should be used cautiously or other short-acting beta-blockers without intrinsic sympathomimetic activity should be consid-ered102ndash104 It is reasonable to recommend cardioversion in patientswith persistent AF after establishment of euthyroid state and in caseof recurrent AF when the patient is euthyroid ablation should be con-sidered101105ndash110 In patients with persistent AF related to hyperthyr-oidism cardioversion results in restoration of sinus rhythm in 88ndash924 in patients without accompanying structural heart disease 86and 67 of them were arrhythmia-free at 3 years and 67 years offollow-up respectively105106
Hyperthyroidism-related AF usually has a lower recurrence ratethan non-hyperthyroidism-related AF In one study where only elec-trical cardioversion was used the risk of AF recurrence was 36lower in hyperthyroidism than in non-hyperthyroidism AF(P = 0004) and the only predictor of AF recurrence was the longerduration of arrhythmia (P lt 001)107 Few studies have reported out-comes of AF ablation108ndash110 with no difference in long-term (4 years)recurrence rate between hyperthyroidism and non-hyperthyroidism-related AF after PV isolation109 while in another study recurrencewas two-fold higher in hyperthyroid than in non-hyperthyroidpatients after single procedure of PV isolation or substrate ablationwhile after multiple procedures there was no difference110
Hyperthyroidism does not independently confer higher risk forstrokesystemic embolic events as compared to non-hyperthyroidpatients111ndash113 and annual risk of stroke in hyperthyroid patientswith AF is lower than in non-hyperthyroid patients114 Warfarinreduced the risk of ischaemic stroke in non-self-limiting AF patientswith hyperthyroidism and CHA2DS2VASc gt_1114
Ventricular arrhythmiasWhile ventricular arrhythmias are rare in hyperthyroid patients oneof the earliest Holter monitoring studies did not demonstrate reduc-tion of ventricular ectopy with antithyroid therapy115 However QTprolongation is described in Graves disease with thyrotoxicosis116
Few cases of isolated VF without structural heart disease and electro-lyte imbalance in hyperthyroidism have been reported117 amongthem coronary vasospasm was confirmed in two one case was due
Table 3 Definitions of thyroid dysfunction6
TSH levels
(mIUL)
Free thyroxine
(pmolL)
Total thyroxine
(mmolL)
Thyroid function
Euthyroidism 02ndash50 9ndash22 60ndash140
Overt hypothyroidism gt50 lt9 lt60
Subclinical hypothyroidism gt50 9ndash22 60ndash140
Overt hyperthyroidism lt02 gt22 gt140
Subclinical hyperthyroidism lt02 9ndash22 60ndash140
TSH level dependent thyroid dysfunction
Euthyroidism 04ndash50 9ndash22 60ndash140
High-normal euthyroidism 02ndash04 9ndash22 60ndash140
Subclinical hyperthyroidism (reduced TSH) 01ndash02 9ndash22 60ndash140
Subclinical hyperthyroidism (suppressed TSH) lt01 9ndash22 60ndash140
TSH thyroid stimulating hormone
10 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
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Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
to amiodarone-induced toxicity and one case was accompanied byearly repolarization All cases were treated with antithyroid therapyprednisolone beta-blockers and in some cases an implantablecardioverter-defibrillator (ICD) was used117 It should be noted alsothat antithyroid therapy might worsen early repolarization andarrhythmia117
BradyarrhythmiasBradyarrhythmias AV block and sick sinus syndrome (SSS) are rareentities in hyperthyroid patients118119 one study reported that only3 of AV block cases with pacemaker implantation were due to pri-mary hyperthyroidism118
Hypothyroidism
Hypothyroidism is accompanied by ventricular arrhythmias and con-duction disturbances One case-control study of 152 hypothyroidand 152 euthyroid patients revealed higher prevalence of VT(P = 004) and ventricular arrhythmias (P = 0007) in hypothyroidpatients120 and Torsades de Pointes with prolongation of QT intervaland bradycardia may develop in hypothyroidism121ndash127 It is advisedto consider hypothyroidism in differential diagnosis of polymorphic
VT The VTVF accompanying hypothyroidism requires correctionwith thyroid hormones DC shock in urgent cases correction of elec-trolyte balance and bradycardia if QT prolongation and Torsades dePointes arrhythmia If arrhythmia is sustained or recurs the implanta-tion of ICD could be considered128
Rarely in patients with implanted pacemakers and ICDs overt orsubclinical hypothyroidism due to functional changes in tissue mightincrease pacing threshold or create exit block in atrial and ventricularpacing leads that usually are reversible by correction of thyroid sta-tus129ndash132
Conduction abnormalities in the setting of hypothyroidism are rep-resented by fascicular blocks (142) 1st degree AV block (119)133
advanced AV block and sinus node dysfunction118134135 There arealso case reports on advanced AV block of 2nd and 3rd degreereversed by thyroid replacement therapy and temporary pace-maker implantation in overt and subclinical hypothyroidism136ndash140
Several reports describe underlying hypothyroidism playing a role indevelopment of lithium-induced sinus node dysfunction reversedafter treatment of hypothyroidism134135 Treatment of subclinicalhypothyroidism should follow the recent update on thyroid diseasemanagement88
Table 4 Evidence summary for arrhythmias associated with thyroid dysfunction
Study Design Subjects Follow-up Thyroid dysfunction Arrhythmia Risk (95CI)
Selmer et al80 Cohort 586 460 55 years Euthyroidism
Overt hyperthyroidism
Subclinical hyperthyroidism
Overt hypothyroidism
Subclinical hypothyroidism
TSH levels
Reduced TSH
Suppressed TSH
High-normal euthyroidism
AF
29
46
25
Reference
IRR 142 (122ndash163)
IRR 131 (119ndash144)
IRR 067 (05ndash09)
IRR 087 (07ndash097)
IRR 116 (099ndash136)
IRR 141 (135ndash189)
IRR 112 (103ndash121)
Colett et al86
Thyroid studies
collaborators
Meta-analysis 52 674 88 years Subclinical hyperthyroidism
Reduced TSH
Suppressed TSH
AF HR 168 (116ndash243)
HR 163 (11ndash24)
HR 254 (108ndash599)
Kim et al90
Framingham Heart
study
Cohort 5055 10 years TSH 045ndash45 lULndash54
TSH 45ndash100 lULndash70
TSH 100ndash199 lULndash40
AF Reference
HR 123 (077ndash197)
HR 057 (021ndash154)
Brandt et al91 Observational
cohort
2631 pts with
hyperthyroidism
10 524 controls
67 years
81 female
6 years HyperthyroidismControls CVD thorn arrhythmia
26
19 P lt 0001
HR 134 (115ndash156)
Kobayashi et al117 Summary
of cases
10 pts
wo CVD and
hypokalaemia
ndash Hyperthyroidism
1 patient with amiodarone-
induced thyroid dysfunction
1 early repolarization
2 cases coronary vasospasm
VF isolated
AF atrial fibrillation CI confidence interval CVD cardiovascular disease HR hazard ratio IRR incidence rate ratio pts patients TSH thyroid stimulating hormone VF ven-tricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 11
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Evidence summary for treatment of arrhythmias associated with thyroid dysfunction
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Effect of antithyroid treatment on arrhythmia
Nakazawa et al98 Prospective 163 pts hyperthyr-
oidism and AF
467 years
Antithyroid therapy -
9
RITthorn antithyroid
therapy -87
Thyroidectomy 3
34 months 101 pts with spontaneous
AF conversion to sinus
rhythm upon attain-
ment of euthyroidism
63 pts
persistent AF
Intervals between return
to euthyroidism and
spontaneous AF con-
version to sinus rhythm
lt1 week 43
1ndash3 weeks 752
4ndash6 weeks ndash 871
7ndash9 weeks ndash 931
10ndash12 weeks ndash 97
13ndash15 weeks 100
gt16 weeks -100
Zhou et al99 Prospective 94 pts
hyperthyroidism
412 years
PAF 38 pts
Pers AF 45 pts
Radioiodine therapy 16 years PAF 0
Pers AF 60
Predictors of pers AF
Age gt55 years
RR 276 116ndash879
P lt 001
Duration of
hyperthyroidism
RR 308 122ndash1141
P lt 001
Duration of pre-treat-
ment AF
RR 296 131ndash768
P lt 001
Tsymbaluk et al100 Prospective 61 pts
hyperthyroidism due
to Graves disease
Antithyroid therapy Euthyroid state AF 25
PAC 7
AF rate before and after
antithyroid therapy
72 to 25 P lt 0001
PAC 71ndash7 P lt 0001
Gauthier et al101 Retrospective 40 pts with hyper-
thyroidism due to
GD and 40
euthyroidism mul-
tinodular goiter
Thyroidectomy Before and after
operation
AF 0 (sinus rhythm in
100)
Sinus tachycardia
-688
ndash
Treatment of persistent AF after antithyroid treatment
Nakazawa et al105 Prospective 33 pts with persis-
tent AF
Cardioversion after
Antithyroid treat-
ment for
hyperthyroidism
35 months AFmdash12
SRmdash88
AF free survivalmdash86
Nakazawa et al106 Retrospective 106 pts with persis-
tent AF
wo SHD
476 years
Cardioversion after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
67 years AFmdash76
SRmdash924
Predictor of AF
recurrence
Duration of AF
HR 16 (114ndash226)
P = 0005
Late follow-up SRmdash67
Siu et al107 Prospective case-
controlled
116 pts
58 hyperthyroidism-
related persistent
AF
58 non-hyperthyoid-
ism AF
ECV after
Antithyroid treat-
ment for 3
months for
hyperthyroidism
24 months ndash AF recurrence
Hyperthyroidismmdash59
Non-hyperthyroidismmdash
83
Risk of AF recurrence
hyperthyroidism vs
non-hyperthyroidism
HR 064 (039ndash097)
P = 0004
Predictor of AF
recurrence
Longer duration of AF
HR 101 (10ndash101)
P lt 001
Continued
12 B Gorenek et al
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Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
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Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 5 Continued
Study Design Subjects Treatment Follow-up Arrhythmia after
treatment
Comment
Machino et al109 Prospective 337 pts
Persistent AF with
history of hyper-
thyroidism 47
(16) wo
hyperthyroidism
953 (321)
First AF ablation
(PVI) after 3
months of antithy-
roid therapy for
hyperthyroidism
4 years ndash AF recurrence
hyperthyroidismmdash44
no hyperthyroidismmdash43
Predictors of AF
recurrence
hyperthyroidism
HR 087 (040ndash188)
P = 073
Wongcharoen
et al110
Prospective 717 pts First AF ablation (PVI
and substrate
modification 12)
gt3 month treatment
of hyperthyroidism
before ablation
ndash AF Predictor of AF recur-
rence after single
procedure
History of
hyperthyroidism
OR 207 (127ndash338)
AF recurrence did not
differ after multiple
procedures
Stroke risk in hyperthyroidism-related AF
Chan et al111 Observational
cohort
AntiT and risk of
ischemic stroke in
hyperthyroidism-
related AF
Of 9727 pts with
non-valvular AF
642 (66) pts with
hyperthyroidism
136 ptsmdashwarfarin
243mdashaspirin
263mdashno AntiT
719 years
678 female
Hyperthyroidism vs
non-
hyperthyroidism
2 years Non-valvular AF Warfarin
Reduced risk of stroke by
67
HR 033 (012ndash091)
Annual risk of stroke by
CHA2DS2Vas score
hyperthyroidism-AF vs
non-hyperthyroid-AF
0mdash0 vs 256
1mdash2ndash317 vs 702
gt_3mdash811 vs 1054
Ischaemic stroke 78
Warfarin reduced risk
of stroke in non-self -
limiting AF
CHA2DS2Vascgt_1mdash
P = 004
But not in self-limiting AF
Bruere et al114 Prospective 8962 pts
with AF
141 hyperthyroidism
history
510 hypothyroidism
history
8271 euthyroidism
929 days AF Stroke SE
hyperthyroidism
HR 085 (041ndash176)
hypothyroidism
HR 098 (073ndash134)
Bleeding
hypothyroidism
HR 13 (102ndash179)
Friberg et al112 Swedish Atrial
Fibrillation
Cohort Study
90 490 patients
No anticoagulation
at baseline
Thyroid disease 84
Thyrotoxicosis
553 pts
15 years AF Ischemic stroke
Thyroid disease
HR 095 070ndash119
Thyrotoxicosis
HR 092 (085ndash105)
StrokeTIAsystemic emboli
Thyroid disease
HR 100 (092ndash109)
Thyrotoxicosis
HR 103 (083ndash128)
Petersen et al113 Retrospective 610 patients Hyperthyroidism Stroke
Within 1 year
after 1 year
AF - 91 (149) Stroke n 1st year after
1st year
Sinus rhythm 8 7
AF 5 7
AF atrial fibrillation AIT amiodarone-induced toxicity AntiT antithrombotic therapy CA catheter ablation CI confidence interval CVD cardiovascular disease ECVelectrical cardioversion HR hazard ratio IRR incidence rate ratio OR odds ratio pts patients RIT radioiodine therapy RR relative risk TIA transient ischaemic attack TSHthyroid stimulating hormone VT ventricular tachycardia VF ventricular fibrillation
EHRA position paper on arrhythmia management in endocrine disorders 13
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
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Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
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Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction
About 103ndash147 of patients taking amiodarone for treatment ofventricular and atrial tachyarrhythmias and 167 of patients receiv-ing amiodarone for control of inappropriate ICD shocks developamiodarone-induced thyroid dysfunction (Table 6)
Amiodarone-induced thyroid dysfunction manifests asamiodarone-induced hyperthyroidism with two distinctive typestype 1 which develops in presence of underlying thyroid disease withexcessive hormone production in response to iodide load associatedwith amiodarone leading to true hyperthyroidism and type 2 destruc-tive thyroiditis that develops due to direct toxic effects if iodine associ-ated with amiodarone Differential diagnosis of two types ofhyperthyroidism usually is done using ultrasonography thyroid I131
uptake and thyroid [99m Tc] 2-methoxy-isobutyl-isonitrile (MIBI)scintigraphy142143 Management of amiodarone-induced thyroid dys-function depends on above-mentioned types of dysfunction with hor-mone replacement therapy for amiodarone-induced hypothyroidismantithyroid medications for amiodarone-induced hyperthyroidismtype 1 and steroids for amiodarone-induced hyperthyroidism type 2(thyroiditis) and use of antithyroid medications and steroids in casesof coexistence of hyperthyroidism and thyroiditis142144 Generallyaccepted approaches in prevention and early detection of
amiodarone-induced thyroid dysfunction are baseline assessment ofthyroid function (thyroxine and TSH levels) before initiation of amio-darone treatment and periodic monitoring of thyroid function (within3 months after initiation and every 3ndash6 months thereafter)145ndash147
though latest studies demonstrated conflicting results with no associa-tion of amiodarone-induced thyroid dysfunction occurrence and peri-odic testing of thyroid hormones it should be mentioned also that495 of patients had detectable abnormalities in thyroid functiontests prior to development of amiodarone-induced dysfunction148
Thyroid stimulating hormone receptor autoantibody test and ultraso-nography may be used for differential diagnosis of type I and type IIthyroid dysfunction147
Overt thyroid dysfunction occurs in 36ndash37 of patientsreceiving amiodarone for prevention of SCD and 103ndash147 ofpatients receiving amiodarone for treatment of ventriculararrhythmias and AF149ndash153 and 167 of patients taking amiodar-one for control of inappropriate ICD shocks154 Meta-analyses ofRCTs on secondary prevention of SCD and adverse effects ofamiodarone in patients treated for ventricular arrhythmiasreported 42ndash57-fold increased risk of thyroid dysfunction and178ndash218 times higher risk for development of bradyarrhyth-mias149150 when compared with placebo groups about 13rdndash1
Recommendations on management of tachy- and bradyarrhythmias associated with
thyroid dysfunction
Consensus
statement
instruction
Level of
evidence
References
Correction of thyroid dysfunction with restoration of euthyroid state is one of the primary goals in the
treatment of tachy- and bradyarrhythmias associated with hyperthyroidism or hypothyroidism
lsquoShould do thisrsquo 98ndash101
Correction of subclinical forms of thyroid dysfunction associated with tachy- and bradyarrhythmias may
be required
lsquoMay do thisrsquo 8891
Referral to endocrinologists should be considered for selection of appropriate thyroid function therapy
(thyrosuppressive therapy radioiodine therapy and thyroidectomy)
lsquoShould do thisrsquo 99ndash101
Hyperthyroidism-related AF that persists after euthyroid condition has been achieved (gt3 months of
thyrosuppressive therapy) should be managed using cardioversion or ablation for rhythm control
Antithrombotic therapy should be applied as for non-hyperthyroid-AF
lsquoShould do thisrsquo 26105ndash114
Rare cases of VTVF in the setting of hyperthyroidism should be managed using antiarrhythmics (caution
with amiodaronemdashsee below) DC shock in cases of hemodynamic compromise and therapy with an
ICD if indicated Associated conditionsmdashcoronary vasospasm early repolarisation amiodarone toxic-
ity should be taken in account
lsquoShould do thisrsquo 95117128
Severe bradyarrhythmias accompanying hyperthyroidism and hypothyroidism might require use of tem-
porary pacemaker in persistent cases after restoration of euthyroid condition bradyarrthythmias
should be managed according to the current guidelines
lsquoShould do thisrsquo 118136ndash141
VTVF accompanying hypothyroidism associated with long QT interval should be managed with correc-
tion of bradycardia and electrolyte imbalance avoid antiarrhythmic drugs that prolong the QT inter-
val In acute cases DC shock may be necessary If VTVF persists therapy with an ICD should be
considered
lsquoShould do thisrsquo 95121ndash128
Monitoring and correction of thyroid dysfunction may be considered if lead dysfunctionchange in atrial
or ventricular pacing thresholds appear in patients with implanted pacemakers and ICDs
lsquoMay do thisrsquo 129ndash132
14 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Summary of evidence for amiodarone-induced thyroid dysfunction
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
Piccini et al149 Met-analysis 15
RCTs of amio
vs placebo effi-
cacy in preven-
tion of SCD
safety
8522 pts
4260 amio arm
4262 placebo arm
12ndash455
months
Thyroid 36 vs 04
Pulmonary 29 vs 15
Hepatic 185 vs 07
Bradyarrhythmias 28
vs15
OR 568 (294-1098) P lt 00001
OR 197 (127-304) P = 0002
OR 21 (115-382) P = 0015
OR 178 (116-272) P = 0008
Amio discontinuation rate 316
Vorperian
et al150
Meta-analysis 4
RCTs amio vs
placebo
Adverse effects
738 pts amio arm
727 pts placebo
arm
low dose amio
100ndash400 mg
maintenance
dose
12ndash45
months
TD 37 vs 04
Bradycardia 33 vs 14
Discontinuation rate 229
vs 154
Skin 23 vs 07
Eye 15 vs 01
OR 423 (204ndash874) P = 0001
OR 218 (111ndash427) P = 0024
OR 160 (123ndash209) P lt00001
OR 248 (105ndash617) P = 005
OR 342 (122ndash364) P = 002
Bathcer et al151
Substudy
of SAFE-T
RCT substudy 612 pts with
persistent AF
Amio vs
Sotalolthorn placebo
1ndash45
years
Hypothyroidism
Subcl 258 vs 66
P lt 00001
Overt 50 vs 03
P lt 0001
Hyperthyroidism
Subcl 1 case amio Overt
53 vs 24 P = 007
ndash
Ross et al152 Cohort study 163 patients
Amio for SVT
102 pts VT 55
pts Prevention
3 pts Uncertain
1 pt
679
days
Hypothyroidism
Subclinical 74
Overt 8
Hyperthyroidism
Subcl 06
Transient hyperthyroidism
06
Overt 67
ndash
Kinoshita et al155 Retrospective
cohort study
For overt thyroid
dysfunctions
Indication for
amio
VA 667ndash80
AA 20ndash333
317 pts
Euthyroid 256
Subcl hypothy-
roid 52
Subcl hyperthy-
roid 9
585 years 735
males
5 years Overt hyperthyroidism
95
Overt hypothyroidism
189
Predictors of hyperthyroidism
DCM OR 33 (126-89)
Sarcoidosis OR 647 (16ndash2577)
Predictors of hypothyroidism
Free T4mdashOR 013 (003ndash068)
TSHmdashOR 147 (126ndash174)
Ahmed et al153 Prospective 303 pts
Amio for AF-260
pts VA 43 pts
63 years 66
males
33 years Hyperthyroidism 8
Hypothyroidism 6
Hyperthyroidism
Age lt62 years
HR 24 (10ndash57) P lt 005
Hypothyroidism
TSH gt14 mUL
HR 51 (11ndash224) P = 003
LVEF lt45
HR 38 (11-133) P = 004
DM-HR 33 (11ndash103) P = 004
Lee et al154 Retrospective
Amio vs sotalol
and beta-
55 pts with ICD
Amio 24 pts
Sotalol 17 pts
4 years Hypothyroidism 167
Time to development
163(23) months
Continued
EHRA position paper on arrhythmia management in endocrine disorders 15
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
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score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
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23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
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29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
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42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
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44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
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EHRA position paper on arrhythmia management in endocrine disorders 25
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57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
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61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
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63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
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69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
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72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
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74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
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77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
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79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
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94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
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95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
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101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
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136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
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clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
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167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Table 6 Continued
Study Design Population Follow-up Thyroid dysfunction
toxicity arrhythmia
Predictors of toxicityOR
RRHR (95CI)
blockers for
inappropriate
shock reduction
in ICD pts
Beta-blockers 19 Treatment
Dose reduction in amio hypo-
thyroidism group and dis-
continuation in pulmonary
toxicity group (167) pts
Shiga et al156 Prospective
Recurrence of VT
VF during amio-
darone induced
toxicity as com-
pared to euthy-
roid state
Holter monitoring
and plasma amio
232 pts
amio therapy
2 years Hypothyroidism 108
No change in arrhythmia
recurrence and plasma
amio
Hyperthyroidism 125
VTVF recurrence euthyroid
1 vs hyperthyroid 9 pts
P lt 001 VPC three-fold
increase P lt 005 No
change in plasma amio
Treatment
Hypothyroidism 12-L-thyro-
xine no discontinuation of
amio
hyperthyroidism 6 methimi-
zole 2 prednisolone 3 amio
discontinuation 18mdashgrad-
ual improvement
Czarnywojtek
et al161
Cohort
RIT for pts on
amio and TD
Amio indication
SVT VT ICD
inappropriate
shocks AF
297 cases amio
A 78 euthyroid-
ism on amio
B118
hyperthyroidism
History amio
C 79 hyperthyr-
oidism amio
D 22
hypothyroidism
12 months Recurrence of hypothyroid-
ism after RIT A 538
B 339 C 341
Recurrence of hyperthyroid-
ism after RIT A 77 B
125 C 114
ABC reinstated amio after
3ndash6 weeks of RIT
D permanent hypothyroid-
ismndashthyroxine replacement
therapy
Diederichsen
et al164
RCT double-blind
placebo-
controlled
Amio vs place bo
for 8 weeks after
catheter ablation
of AF
Endpoint TD
212 patients after
catheter ablation
of AF without
history of thy-
roid dysfunction
Amio group 8
weeks amio
Placebo group
6 months Thyroid dysfunction
Amio discontinuation
Amio groupmdash3
Placebomdash1
Amio group significantly
higher TSH fT4 and T4 and
lower fT3 and T3 at 1 and 3
months as compared to
placebo
TD after 1 month of amio
treatment
AA atrial tachyarrhythmias AF atrial fibrillation Amio amiodarone CI confidence interval CVD cardiovascular disease DM diabetes mellitus ECV electrical cardioversionHR hazard ratio ICD implantable-cardioverter defibrillator IRR incidence rate ratio LVEF left ventricular ejection fraction OR odds ratio pts patients RCT randomizedcontrolled trial RIT radioiodine therapy RR relative risk subcl subclinical SVT supraventricular tachycardia TD thyroid dysfunction TSH thyroid stimulating hormone VAventricular arrhythmia VPC ventricular premature complexes VT ventricular tachycardia VF ventricular fibrillation
16 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
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12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
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23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
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29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
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44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
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98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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4th of patients discontinued amiodarone treatment Amiodarone-induced thyroid dysfunction includes overt and subclinical hypo-thyroidism and hyperthyroidism151152 although changes in thy-roid hormone levels in euthyroid patients on amiodaronetreatment are common without clinical manifestations ofamiodarone-induced thyroid dysfunction142 In the SAFE-T(Sotalol-Amiodarone Fibrillation Efficacy) trial overt hypothyr-oidism developed in 50 subclinical hypothyroidism in 258 andovert hyperthyroidism in 53 and itrsquos subclinical form only in onepatient in amiodarone arm that were significantly higher than incontrol arm receiving sotalol or placebo for treatment of persis-tent AF (P lt 005 for all)151 In another cohort study of patientsreceiving amiodarone for ventricular and atrial tachyarrhythmiassubclinical and overt hypothyroidism developed in 74 and 8 ofpatients respectively and subclinical and overt hyperthyroidismin 06 and 67 respectively after 943 days of treatment152
Though the evidence on predictors of amiodarone-induced thy-roid dysfunction is limited two studies153155 addressed the issueof identifying patients at risk of thyroid dysfunction in one studypatients with low thyroxine and high TSH levels were at risk ofhypothyroidism development while patients with dilated cardio-myopathy and sarcoidosis had 33 and 647-fold increased risk ofhyperthyroidism development155 it should be noted that patientswith subclinical thyroid dysfunction at baseline were also included
in the study In another prospective study of patients with AF andventricular arrhythmias receiving amiodarone 8 of patientsdeveloped hyperthyroidism and 6 of patientsmdashhypothyroidismduring 33 years of follow-up and the only predictor for develop-ment of hyperthyroidism was age lt62 years while hypothyroidismrisk was associated with TSH levels gt14 mUL low ejection frac-tion and DM153
In summary amiodarone-induced overt thyroid dysfunctionoccurs in approximately 103ndash147 of patients with arrhythmiasreceiving amiodarone and should be suspected if symptoms of toxic-ity develop including tachy- and bradyarrhythmias other organslesions and change in thyroid tests (Table 3)
Of note amiodarone-induced thyroid dysfunction depends neitheron dose150 nor on plasma concentration of amiodarone156 buttachy- and bradyarrhythmias may occur Holter monitoring study inpatients with VTVF receiving amiodarone treatment demonstratedstatistically significant increase in recurrence of VT and ventricularpremature complexes in hyperthyroid state when compared withbaseline euthyroid state156 and in rare cases of thyroid storm VTVFmay develop128 Withdrawal of amiodarone and switching to otherantiarrhythmic drugs can be effective in treatment of VTVF episodesdue to amiodarone-induced thyroid dysfunction157
Bradyarrhythmias usually occur in hypothyroidism AV block tendsto develop in presence of pre-existing conduction abnormality77
Recommendations on management of amiodarone-induced thyroid
dysfunction
Consensus
statement
instruction
Level of
evidence
References
Before prescribing amiodarone therapy for long-term use it is recommended to weigh risk
benefit of its toxicity and strongly consider catheter ablation to cure or modify the sub-
strate for arrhythmias instead
lsquoShould do thisrsquo 145149ndash151
It is recommended to carry out baseline thyroid tests (thyroxine and TSH) before initiation
of amiodarone treatment) thyroid-directed autoantibodies and ultrasonography should be
considered for differential diagnosis of type I and type II amiodarone-induced
hyperthyroidism
lsquoShould do thisrsquo 116117119120142
143145ndash147163
It is advised to monitor thyroid function tests and ECG for amiodarone-induced thyroid dys-
function screening
lsquoShould do thisrsquo 145147148
If hyperthyroidism occurs during treatment with amiodarone its discontinuation
MANDATORY The eventual decision to initiate or continue amiodarone once the euthy-
roid state is achieved for preventing life-threatening ventricular tachyarrhythmias should
be carefully evaluated in each individual case in terms of expected risk and benefits
lsquoDo not do thisrsquo 142143145154161165
Hypothyroidism should be treated with thyroid replacement agents and amiodarone therapy
may be continued if necessary
lsquoShould do thisrsquo 145156165
In case of VTVF withdraw amiodarone and treat using antiarrhythmics and DC shock if
hemodynamic compromise
lsquoShould do thisrsquo 128156
The use of amiodarone in elderly patients increases the risk of bradyarrhythmias such as
advanced AV block or SSS requiring a permanent pacemaker
lsquoShould do thisrsquo 141160
EHRA position paper on arrhythmia management in endocrine disorders 17
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
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12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
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22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
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27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
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44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
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95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
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98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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Amiodarone-induced thyroid dysfunction may manifest as SSS consti-tuting 22 of all causes of SSS158ndash160 In some circumstances correc-tion of thyroid dysfunction in patients with AF and bradycardiadeveloped on amiodarone treatment unmasks underlying tachycardia-bradycardia syndrome159
Withdrawal of amiodarone therapy should be strongly considered incases of hyperthyroidism proper management of VTVF AV block andSSS is required In a study of amiodarone-induced thyroid dysfunction inpatients receiving amiodarone for prevention of inappropriate shocksdose reduction of amiodarone was adequate to reduce signs ofamiodarone-induced thyroid dysfunction154 Latest studies on use ofantithyroid therapy in patients requiring long-term amiodarone treat-ment (ventricularatrial arrhythmias or inappropriate shock reduction inICD patients) demonstrated that application of antithyroid radioiodinetherapy might be an option to reinstitute amiodarone treatment161radioiodine ablation of thyroid is also an option in amiodarone-inducedthyroid dysfunction with resistant tachyarrhythmias162
It is recommended also to weigh the risk of amiodarone-inducedthyroid dysfunction before considering the long-term treatment orprefer treatment like catheter ablation Monitoring of thyroid func-tion every 6 months and electrocardiogram follow-up in patients onamiodarone therapy should be considered145148163
PheochromocytomaThe prevalence of pheochromocytoma (PCC) discovered duringlife is 015ndash04 however many cases remain undiscovered asthe prevalence noted in autopsy studies is higher166 The clinicalpicture ranges from totally asymptomatic patients to life-threatening complications including MI severe heart failure
Tako-tsubo cardiomyopathy and arrhythmias Typically addi-tional release of catecholamines by PCC is accompanied by par-oxysmal headache sweating hypertension and palpitationsTherefore recurrent arrhythmias in such clinical context shouldraise the suspicion of PCC Palpitations are present in one-halfto 70 of patients167
Arrhythmia mechanisms include beta-adrenergic stimulation ofthe heart alpha1-adrenergic stimulation (especially during myo-cardial ischemia and reperfusion)168 desensitization of adrenergiccardiovascular receptors due to prolonged adrenergic stimulationand reflex increase in vagal tone Most often sinus tachycardia isencountered However a large spectrum of arrhythmias could bepart or the first clinical manifestation of PCC before typical signsare present It includes mostly supraventricular arrhythmias andAF but also malignant and bidirectional VT169 Some PCC patientsmanifest with reflex bradycardia asystole AV dissociation Wolf-Parkinson-White syndrome or SSS170 Patients with PCC maypresent with repolarization abnormalities consisting of markedQT prolongation and deep wide inverted T wave171 with subse-quent risk for Torsades des Pointes
Esmolol a beta1-adrenergic cardioselective blocker with rapidonset of action can be used to control fast rate due to AF or atrialflutter (05 mgkg iv followed by continuous infusion of 01ndash03 mgkgmin)170 Associated alpha-blockade (ie phenoxybenzamine 10 mgonce to 10ndash30 mg twice or a1 blockade with prazosinmdashstarting with1 mg and increasing to 1 or 2 mg two or three times daily) may beused to prevent the incidence of hypertensive crisis during betablockade There is no specific treatment for other arrhythmias andVT could respond to lidocaine172
Recommendations on management of PCC Consensus
statement
instruction
Level of
evidence
References
Pheochromocytoma should be considered as possible diagnosis in patients with paroxysmal
headache hypertension palpitations and recurrent arrhythmia
lsquoShould do thisrsquo 167
Esmolol should be used to control rapid rate in AF and flutter Associated alpha blockade is
mandatory to prevent hypertensive crisis
lsquoShould do thisrsquo 170
Lidocaine may be used to treat sustained VT lsquoMay do thisrsquo 169172173
As PCC can prolong QTc interval antiarrhythmic drugs prolonging the QTc should be used
with caution and only after QTc monitoring
lsquoShould do thisrsquo 171
18 B Gorenek et al
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Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
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QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Growth hormone dysfunctionAcromegaly
Acromegaly is a rare and debilitating disease with a prevalence of 40 permillion characterized by increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Early clinical trials have demonstrated atwo-fold increase in overall mortality in patients with acromegaly whencompared with general population with cardiovascular causes account-ing for 40ndash60 of all deaths174ndash176 Acromegalic cardiomyopathy ischaracterized by biventricular hypertrophy progressing to diastolic andsystolic dysfunction culminating in heart failure in 10 of patients177ndash179
Recent cohorts with patients treated early in the disease course sug-gest lower rates of cardiovascular involvement180181 Classically mono-nuclear cell infiltration182 apoptosis183 myofibrillary abnormalities184
interstitial fibrosis oedema and cardiomyocyte hypertrophy are charac-teristic of acromegalic cardiomyopathy and may represent the histologi-cal substrate for arrhythmias184185
Cardiac arrhythmias in acromegalyThere is paucity of data on the prevalence and severity of cardiacarrhythmias in acromegaly186ndash188 Supraventricular arrhythmias areuncommon in patients with acromegaly with one study reportingsupraventricular arrhythmias in 627 patients while two other showabsence of any increase188ndash190 Asymptomatic sinus node disease hasalso been described in a small proportion of patients in anotherstudy191 However complex ventricular ectopy is common occur-ring in 40ndash48 of acromegalic patients188189192 and increasing withexercise188 The ventricular ectopy increased with duration of
acromegaly and severity of ectopy correlated with left ventricularmass but not GH levels188 Sustained VT and sudden death has beenreported in patients with acromegaly with severe cardi-omyopathy193ndash195 Late potentials are common in acromegalic cardi-omyopathy and correlate with frequency of ventricular ectopy181192
Similarly greater QT dispersion (dQT) and prolonged QTc intervalare seen in active acromegaly and may predispose to ventriculartachyarrhythmia196197
Impact of acromegaly specific treatment on cardiac arrhythmiasThere is lack of longitudinal studies evaluating the impact of treat-ment of acromegaly on associated cardiac arrhythmia Howeverthere is indirect evidence to suggest that control of acromegaly inearly stages may decrease cardiac remodelling180 development oflate potentials181 ventricular arrhythmia198ndash200 and cardiacmortality201
Growth hormone deficiency
Growth hormone deficiency is diagnosed in 01 of the population ingeneral clinical practice and is characterized by the short stature frontalbossing central obesity and high-pitched voice202 Growth hormonedeficiency usually manifests early in childhood while in adults it may beaccompanied by increased sensitivity to insulin in patients with diabetesand manifests with fine wrinkling around eyes and mouth Deficiency ofGH adrenocorticotropic hormone and gonadotropin and hypothyr-oidism are common in hypopituitarism203 Though rarely tachy- andbradyarrhythmias may accompany GH deficiency204205 In one prospec-tive study of pituitary hormone levels in patients who underwent
Aldosterone excess
BaroreceptorsCathecholexcess
Cardiacfibrosis
Cardiac failure Diastotlic andsystolicdysfunction
Na+ H2Oretention
K+ Mg++
loss
Fibrosis andvascularreactivity
Hypertension
Congestion
Arrhythmias
LVH
Figure 4 Effect of aldosterone on the cardiovascular system215 Cathechol cathecholamine LVH left ventricular hypertrophy
EHRA position paper on arrhythmia management in endocrine disorders 19
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cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
cardiopulmonary resuscitation due to VTVF GH deficiency waspresent in 275 of them204 with (GH)-IGF-1 being significantly lowerin a group of patients with GH deficiency when compared with groupof patients with normal GH values There are also reports on increasedcardiovascular morbidity in children with GH deficiency treated withGH due to cardiomegaly205 A complete AV block was described in achild with GH deficiency during therapy with hGH treated successfullyby pacemaker implantation205
Thus cardiac evaluation and monitoring is reasonable in patientswith GH deficiency and during its therapy
Diseases of adrenal cortexHyperaldosteronism
Primary hyperaldosteronism (PH) also known as Connrsquos disease isan endocrine disorder caused by an adrenal adenoma (uni- or bilat-
eral) It causes hypertension hypokalaemia metabolic alkalosis andrenin suppression206ndash208 Long-standing PH has been associated withmyocardial injury leading to heart failure and either atrial or ventricu-lar arrhythmias209ndash214 Figure 4 summarizes the effect of aldosteroneon the cardiovascular system215
Management of PH associated arrhythmias focuses on controllingmetabolic and electrolyte disturbances216 Deleterious cardiovascu-lar effects can be controlled by either performing aldosterone recep-tor blockade or adrenalectomy217 Tables 7 and 8 summarize PHrelated arrhythmias
Specific data on indications for device implantation in PH patientsis very limited and general guideline recommendations apply for thispopulation The main treatment approach for this condition is eithersurgical resection of the adrenal adenoma or pharmacological ther-apy targeting adrenal hyperplasia207ndash210
Adrenal insufficiency
Primary adrenal insufficiency (PAI) also known as Addisonrsquos diseaseit is characterized by corticosteroid and mineralocorticoiddeficiency230231 Patients with PAI typically present with hyponatrae-mia hyperkalaemia hypoglycaemia and hyperpigmentation Cardiacmanifestations include hypotension syncope arrhythmias and cardi-omyopathy Acute exacerbations are called Addisonian crises232
Table 9 summarizes the most common cardiac abnormalities andECG findings which are usually reversible with definitive treatmentof the underlying cause231233
Recommendations Consensus
statement
instruction
Level of
evidence
References
Primary hyperaldosteronism patients with atrial or ventricular arrhythmias should receive
treatment for stabilization of their electrolyte and metabolic disturbances
lsquoShould do thisrsquo 216217
In PH patients with persistent rhythm abnormalities or myocardial damage pacemakers or
high voltage devices may be used according to life expectancy and response to optimal
medical therapy
lsquoMay do thisrsquo 218225226
Table 8 Description of the most important studies on PH
Study Type of study Number of
patients (n)
AF () VT () Sustained
arrhythmias ()
Milliez et al212 Case control 124 73 NA NA
Catena et al228 Prospective cohort 54 NA NA 15
Born et al222 Retrospective cohort 640 71 NA NA
Mulatero et al221 Case control 270 NA NA 78
Savard et al229 Case control 459 39 NA NA
AF atrial fibrillation NA data not available PH primary hyperaldosteronism VT ventricular tachycardia
Table 7 Electrocardiographic disorders associatedwith PH
Prolonged QT-interval218
Atrial fibrillation219220
Atrial flutter221
Ventricular tachycardia222
Polymorphic ventricular tachycardia223224
Ventricular fibrillation225ndash227
PH primary hyperaldosteronism
20 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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Parathyroid diseaseHypoparathyroidism and hyperparathyroidism are rare hormone dis-orders characterized by abnormally low or high levels of the parathy-roid hormone (PTH) Physiologically PTH plays a critical role in the
regulation of calcium homeostasis through several mechanisms Theconsequence of PTH deficiency is hypocalcaemia which can causeQT interval prolongation and arrhythmias In clinical practice how-ever torsades de pointes or other life-threatening tachyarrhythmiasare infrequent in patients with hypoparathyroidism despite extremeQT prolongation242 In the literature there is only one case report ofa patients with hypoparathyroidism who suffered VF probably due toheart failure and severe hypocalcaemia243 Severe hypocalcaemiarequires treatment as soon as possible with intravenous calciumLong-term treatment of hypoparathyroidism includes calcium andVitamin D supplementation for the stable control of plasma calciumlevels243
The main biochemical feature of primary hyperparathyroidism ishypercalcaemia Hypercalcaemia may induce arrhythmias throughboth early and delayed ventricular after depolarization Previousstudies have shown that primary hyperparathyroidism and hypercal-caemia are directly related to electrocardiographic abnormalitiessuch as high-amplitude QRS complex short ST segment and QTinterval and T wave extension244 A variety of arrhythmias such assinus arrest supraVT and AF has been documented in patients withprimary hyperparathyroidism245 Furthermore ventricular arrhyth-mias in association with hyperparathyroidism have been reportedincluding ventricular bigeminy VT and VF246ndash248 Although patientswith hyperparathyroidism have an increased risk of death it is notknown if arrhythmias play any role in increased cardiovascular mor-tality The most effective method for the treatment of primary hyper-parathyroidism is parathyroidectomy However the role of surgeryregarding the effect on cardiac arrhythmia risk is controversial Somestudies did not report a reduced incidence of mortality in hyperpara-thyroidism after parathyroidectomy while the other showed thatparathyroidectomy reduced the occurrence of ventricular arrhyth-mias and restored the QTc adaptation during exercise test249ndash251
A series of case reports indicate that in rare cases ventricular storminduced by hyperparathyroidism may be controlled only after para-thyroid surgery247248252253
Sex hormones-related differences in therisk of arrhythmiasIt is well recognized that men and women differ with respect to therisk of developing arrhythmias3254ndash256 The mechanisms involved inthese differences have not been fully elucidated but may be relatedto the electrophysiological effects of sex hormones In experimentalstudies257258 17b-oestradiol has protective effects on ischemia-induced arrhythmias and reduces L-type Ca2thorn current (ICaL)Nevertheless estrogens may partially suppress the delayed rectifierKthorn current (IKr) thus enhancing drug-induced APD and QTc prolon-gation Progesterone increases slow activating delayed rectifier Kthorn
current (IKs) and modulates ICaL therefore promoting APD short-ening Testosterone also regulates both IKs and ICaL in a dose-dependent manner and results in shortening of APD257258
Women have higher resting heart rate shorter PR and QRS inter-vals and longer QTc intervals whereas men more frequently exhibitearly repolarization3254ndash256 Notably repolarization differencesbetween men and women do not occur in prepubertal children259
Repolarization is also affected by the ovarian cycle since repolarizingcurrents are increased by progesterone and decreased by oestrogen
Table 9 Cardiac abnormalities associated with PAI
Idiopathic dilated cardiomyopathy234
Tako-tsubo cardiomyopathy235
ECG
Low voltage236
Sinus bradycardia237
Prolonged PR-interval237
Prolonged QT-interval238
T-wave inversion239
Brugada like-pattern240
Polymorphic ventricular tachycardia241
Ventricular fibrillation237
ECG electrocardiogram PAI primary adrenal insufficiency
Recommendations Consensus
statement
instruction
Level of
evidence
References
Patients with PAI and ECG
changes should be treated
for electrolyte and meta-
bolic disturbances
lsquoShould
do thisrsquo
230
Patients with PAI in the set-
ting of dilated cardiomy-
opathy andor heart
failure who receive opti-
mal medical therapy
should be started on
hydrocortisone and flu-
drocortisone
Fludrocortisone should be
used with caution
because excessive fluid
retention may lead to or
worsen heart failure
symptoms
lsquoShould
do thisrsquo
231232
Patients with PAI and persis-
tent rhythm abnormalities
or myocardial damage
may be candidates for
pacemakers or high volt-
age device therapy based
on life expectancy and
response to optimal medi-
cal therapy
lsquoMay do thisrsquo 233
EHRA position paper on arrhythmia management in endocrine disorders 21
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
QTc is longer in the follicular phase when compared with the lutealphase255258 The longer repolarization renders women more suscep-tible to drug-induced Torsades de Pointes260 Therefore QT pro-longing drugs should be used carefully in females particularly in thosewith other abnormalities such as electrolyte imbalance Accordinglyprogesterone may attenuate drug-induced QTc lengthening261 Alsowomen have greater arrhythmic risk than men in congenital LQTSespecially after puberty262 Further emphasizing the role of hormonalmodulation in arrhythmia development in congenital LQTS the riskof life-threatening events is reduced during pregnancy but increasedin the postpartum period263 On the other hand Brugada syndromeand AF predominate in men254ndash256 It is well known that women havea higher incidence of AV nodal re-entry tachycardia and inappropri-ate sinus tachycardia264 Exacerbation of supraventricular tachycar-dias may occur during pregnancy likely due to hormonal andautonomic tone changes265
Stroke risk assessment andprevention in arrhythmiasassociated with endocrinedisorders
As described in previous sections the presence of various endocrinedisorders can be associated with AF which is the arrhythmia mostcommonly associated with increased risk of stroke andthromboembolism
Older small studies113 have suggested an association between thy-roid disease and an increased risk of stroke in AF In the largest analysisfrom the Swedish AF cohort study112 a nationwide cohort of 182 678subjects with AF thyroid disease (HR 095 95 CI 085ndash105) or
thyrotoxicosis (HR 092 95 CI 070ndash119) were not independentpredictors of ischaemic stroke in multivariate analysis Similarly eitherthyroid disease or thyrotoxicosis were not independent predictors ofmajor bleeding or intracranial haemorrhage Similar observationswere noted in the Loire Valley AF project where history of hyper-thyroidism was not an independent risk factor for strokesystemicembolism whereas hypothyroidism was associated with a higher riskof bleeding events114 Thus AF patients with thyroid disease are asso-ciated with stroke or thromboembolism only in association with otherestablished stroke risk factors the most common of them areincluded within the CHA2DS2-VASc score266 Similar for stroke orthromboembolism risk assessment should be used to identify patientsat risk for bleeding and to address the potentially reversible bleedingrisk factors as advocated by validated practical bleeding risk scoressuch as the HAS-BLED score267
Diabetes mellitus is well established as a clinical stroke risk factorin AF and is incorporated into the CHA2DS2-VASc score266268
Duration of diabetes may accentuate stroke risk but not bleedingrisk269 Indeed duration of diabetes may be a more important predic-tor of ischaemic stroke than glycaemic control in such patients270
Whilst diabetic complications such as diabetic retinopathy areassociated with higher risks such evidence of lsquodiabetic target organdamagersquo does not independently add to stroke or bleeding riskprediction271
With regard to prevention of stroke the most important measureis oral anticoagulation (OAC) whether given as a Vitamin K antago-nist (VKA eg warfarin) with good quality anticoagulation control(with ldquotime in therapeutic rangerdquo or TTR gt70) or a non-VKA oralanticoagulant (NOAC eg dabigatran rivaroxaban apixaban oredoxaban) The NOACs are the preferred option in most patientsstarting anicoagulation but given the heterogeneity of AF patientsand the availability of different OAC options we should fit the drugto the patient profile In general NOACs appear relatively moreeffective and safer than VKA in reducing strokesystemic embolismand major bleeding irrespective of patient comorbidities272
In summary AF stroke risk stratification even with concomitantendocrine disorders should use the established CHA2DS2-VAScscore266 to initially identify lsquolow riskrsquo patients (CHA2DS2-VASc 0 inmales or 1 in females) who do not need any antithrombotic therapyfollowed by prevention of stroke (ie OAC) in patients with gt1 riskfactor
As OAC is being initiated a clinical bleeding risk score such asHAS-BLED score (see above) should be used to identify patients atrisk for bleeding and importantly to address the potentially reversi-ble bleeding risk factors (that should be considered in all patientsirrespective of HAS-BLED score value) The next step is to considerchoice of OAC and the SAMe-TT2R2 score273 can be used to aiddecision making between a VKA with likelihood of a good TTR (score0ndash2) or those less likely to achieve it thus requiring more regularINR checks or as a better option use of a NOAC274 This simplethree-step pathway has been advocated to help streamline decisionmaking for stroke prevention in AF274
Recommendations Consensus
statement
instruction
Level of
evidence
References
QT prolonging drugs (www
crediblemedsorg) should
always be used carefully in
both women and men
However due to an
increased risk of drug-
induced Torsades de
Pointes this recommenda-
tion should be further
emphasized for women
particularly in the pres-
ence of electrolyte
imbalance
lsquoShould
do thisrsquo
260261
22 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Catheter ablation of arrhythmiasassociated with endocrinedisorders
Catheter ablation for atrial or ventricular arrhythmia is optimally per-formed in as much as possible stable electrolytic and metabolic con-ditions in order to avoid transient arrhythmias Arrhythmiasassociated with endocrine disorders would theoretically need noablation since they are supposed to spontaneously disappear oncereturn to steady state is obtained They may also alter the analysis oftargets to be ablated and interpretation of results for complex proce-dures However ablation sometimes needs to be performed inpatients with acute or subacute endocrine disorders This may applyto patients with severe ventricular tachyarrhythmia and electricalstorm or atrial tachyarrhythmia with haemodynamic compromisenot efficiently treated with other methods
DiabetesA meta-analysis of 15 studies and 1464 patients indicated that cathe-ter ablation of AF in patients with diabetes had similar safety and effi-cacy than that in the general population especially when performedin younger patients with satisfactory glycaemic control29 Catheterablation of AF reduces the amount of patients requiring antiarrhyth-mic drugs an additional benefit in a population commonly exposedto adverse effects of AF pharmacological treatments
Thyroid disordersFT4 levels may influence the success rate of AF ablation procedureseven within the normal range275276 It has been found that right atrialnon-PVs triggers were more prevalent in AF patients treated withthyroid hormone replacement After elimination of non-PV triggersthere was still a worse arrhythmia-free survival in these patients277
Patients with hyperthyroid history have a higher number of PVectopic beats and higher prevalence of non-PV ectopic foci com-pared with euthyroid patients which may result in a higher AF recur-rence rate after ablation procedure110 Catheter ablation for
paroxysmal AF in patients with amiodarone-induced hyperthyroidismis usually safe and effective albeit with higher rate of early AF recur-rences up to 3 months after PV isolation relative to controls but notbeyond 12 months278 Pulmonary vein isolation alone may have alower efficacy for preventing recurrence in paroxysmal AF in thesepatients with amiodarone-induced hyperthyroidism which may needrepeat ablations279
Device-based therapy ofarrhythmias in patients withendocrine disorders
Diabetes and long-term treatment with chronic corticosteroids (fre-quently prescribed in endocrine disorders) are important factorsassociated with an increased risk of infections of cardiac electricalimplanted devices (CIEDs) as shown in Table 8280ndash284 Pacemaker-and ICD-related infections represent one of the most difficult compli-cations that may occur in a patient implanted with a CIED There isincreasing concern on the important clinical and economic conse-quences of the rise in the incidence of CIEDs-related infections thathave occurred in the last 10 years280ndash284 The incidence of pace-maker- and ICD-related infections has been reported to rangebetween 01 and 199 for pacemakers and between 08 and95 for ICDs including biventricular devices in observational studieswith different follow-up durations280ndash284 Cardiac electrical implanteddevices infections usually appear as infections limited to the devicepocket often with fistulas and skin erosion but lead endocarditis maybe detected in around one out of 10 cases with an incidence of 006ndash06280ndash284 The outcome of CIED infections is characterized by seri-ous events including a high risk of death so preventive measures aremandatory on the basis of appropriate identification of risk factors(Table 10)
In patients with an ICD or a device for cardiac resynchronizationtherapy (CRT) implanted diabetes influences outcome similarly toother comorbidities included in the Charlson comorbidity score285
The comorbidities that are represented in the Charlson comorbidity
Recommendations Consensus
statement
instruction
Level of
evidence
References
Irrespective of underlying endocrine abnormalities (which should be concurrently managed)
the CHA2DS2-VASc score should be used to initially identify lsquolow riskrsquo patients
(CHA2DS2-VASc 0 in males or 1 in females) who do not need any antithrombotic therapy
followed by prevention of stroke (ie OAC) in patients with gt1 risk factor
lsquoShould do thisrsquo 266274
As OAC is being initiated a clinical bleeding risk score such as HAS-BLED score should be
used to identify patients at risk for bleeding (HAS-BLED gt_3)
lsquoShould do thisrsquo 266267274
Importantly potentially reversible bleeding risk factors should be considered in all patients
irrespective of HAS-BLED score value
The SAMe-TT2R2 score may be used to aid decision making between a VKA with likelihood
of a good TTR (score 0ndash2) or those less likely to do so thus requiring more regular INR
checks or as a better option use of a NOAC
lsquoMay do thisrsquo 273274
EHRA position paper on arrhythmia management in endocrine disorders 23
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
score are independent predictors of death all-cause and cardiovas-cular hospitalizations as well as of days spent alive and out of hospi-tal286 In a report from the United States on more than 18 000patients with a cardiac resynchronization therapy-defibrillator (CRT-D) device implanted patients with diabetes had a higher mortalitythan those without diabetes both at 1 and 3 years287 in agreementwith a meta-analysis based on five studies on cardiac resynchroniza-tion in heart failure288289 However these findings have to beanalysed in combination with the evidence derived from randomizedstudies that CRT is equally effective in reducing mortality vs controlin diabetic as compared to non-diabetic patients288290
The effectiveness of ICDs for primary prevention of SCD inpatients with diabetes has raised great interest since diabetes as wellas other comorbidities may be also associated with a high risk ofnon-arrhythmic cardiac and non-cardiac death This complex topichas been studied through subanalysis of randomized trials systematicreviews and meta-analysis291 The subanalysis of diabetic patients inrandomized clinical trials provides reassurance since the beneficialeffect of ICD on survival is confirmed both in patients with and with-out diabetes291ndash293 The frequent association between diabetes andchronic kidney disease (CKD) is of great relevance since CKD per semay condition the outcome and the benefits after implant of a ICDor a CRT device294
In patients implanted with a defibrillator the occurrence of AF dueto hyperthyroidism may induce inappropriate shocks and requiresproper management258 Hyperthyroidism either due to primary
thyroid disease or secondary to amiodarone treatment should beexcluded in any case of new-onset of atrial tachyarrhythmias295296
Hypothyroidism has been associated with poor outcomes inpatients with heart failure and therefore it is of interest to assess theoutcome of patients with previous diagnosis of hypothyroidism afterCRT device implantation In a case series of heart failure patientsimplanted with CRT a history of hypothyroidism was present in164 and was an independent predictor of poor outcome (cardiacdeath heart failure hospitalization or need for heart transplant)297298
Current research gaps ongoingtrials and future directions
Most of the information present in the literature is based on registriesand the communication of some exceptional cases Mostly there areno data on the specific effect of hormones on heart rate disturbancesand their effects are estimated based on structural remodelling andassociated comorbidities (ie changes in blood pressure obesitysleep disorders or increased catecholamine levels) Importantlythere is scarce evidence of the real incidence of arrhythmias in endo-crine diseases Indeed the lack of clinical trials with specific attentionto the effect on arrhythmias is general Specific randomized trials areneeded beyond drug safety where only the effect on heart rhythmdisturbances is very marginal
Different trials are searching for the biological effect of antidiabeticdrugs on heart rhythm For example it has led to study the effects ofintravenous exenatide on cardiac repolarisation299 exploring changes toQTc interval changes In the same line Addhope 2 trial300 studies theheart rate variability modifications with liraglutide in patients with ischae-mic heart disease and newly diagnosed DM type 2
An interesting field is the diagnosis of AF in patients treated forhyperthyroidism In this setting there is a thumb-ECG ambulantscreening for AF in this type of patients301 though in clinical settingother monitoring methods can be used Whereas TABLAS studyexplores the influence of subclinical hyperthyroidism on the resultsof AF ablation302
Regarding PCC the PRESCRIPT trial compares phenoxybenzaminevs doxazosin and assesses the differences in high blood pressure andtachycardia episodes303 There is also an ongoing study in acromegalypatients it is exploring the effects of repeated subcutaneous injectionwith BIM23B065mdasha somatostatin 2 receptor agonist-in acromegalicpatients304 on blood pressure heart rate and QT interval
Cardiac arrhythmias in endocrine disorders are frequent and mod-ify the natural history of the disease These facts invite cardiologists toparticipate in future research and trials to explore pathophysiologicpathways diagnosis and therapeutic approach in endocrine disorders
Supplementary material
Supplementary material is available at Europace online
AcknowledgementsThe authors thank EHRA Scientific Documents Committee GregoryYH Lip Laurent Fauchier David Arnar Carina Blomstrom-Lundqvist Zbigniew Kalarus Gulmira Kudaiberdieva Georges H
Table 10 Risk of CIED infection according to aseries of risk factors as reported in literature280ndash284
Odds ratio for
the risk of
CIED infection
Patient factors
Male gender 15
Younger age 14ndash45
Diabetes 23ndash35
Chronic kidney disease 46ndash63
Haemodialysis 86
Treatment with anticoagulants 26ndash34
Chronic corticosteroid use 91
History of malignancy 40
Underlying heart disease 31
High Charlson co-morbidity index 27ndash30
Fever systemic infection 58
Device or procedure-related factors
Prior CIED infection 113
gt_3 implanted leads 40ndash54
Device replacement device upgrades
or implant revision
17ndash31
Early reinterventions 27ndash15
Temporary pacing prior to implantation 25
Post-operative haematoma at pocket site 40ndash67
Physician experience 25
CIED cardiac electrical implanted device
24 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
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4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
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27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
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29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
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47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
Mairesse Tatjana Potpara Irina Savelieva Jesper Hastrup SvendsenVassil B Traykov
Conflict of interest none declared
References1 Lengyel S Vira L Kova PP Kristo A Pacher P Kocsis E Role of slow delayed
rectifier K-current in QT prolongation in the alloxan-induced diabetic rabbitheart Acta Physiol 2008192359ndash62
2 Ballou LM Lin RZ Cohen IS Control of cardiac repolarization by phosphoino-sitide 3-kinase signaling to ion channels Circ Res 2015116127ndash37
3 Boriani G Lorenzetti S Cerbai E Oreto G Bronzetti G Malavasi VL et al Theeffects of gender on electrical therapies for the heart physiology epidemiologyand access to therapies a report from the XII Congress of the ItalianAssociation on Arrhythmology and Cardiostimulation (AIAC) Europace 2017191418
4 Gilles AM Atrial fibrillation and ventricular arrhythmias sex differences in elec-trophysiology epidemiology clinical presentation and clinical outcomeCirculation 2017135593ndash608
5 Lang F Shumilina E Regulation of ion channels by the serum and glucocortoidinducible kinase SGK1 FASEB J 2013273ndash12
6 American Diabetes A 9 Cardiovascular disease and risk management DiabetesCare 201740(Suppl 1) S75ndash87
7 Malmberg K Yusuf S Gerstein HC Brown J Zhao F Hunt D et al Impact ofdiabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction results of the OASIS (Organization to AssessStrategies for Ischemic Syndromes) Registry Circulation 20001021014ndash9
8 Scirica BM Bhatt DL Braunwald E Raz I Cavender MA Im K et al Prognosticimplications of biomarker assessments in patients with type 2 diabetes at highcardiovascular risk a secondary analysis of a randomized clinical trial JAMACardiol 20161989
9 Tse G Lai ET Tse V Yeo JM Molecular and electrophysiological mechanismsunderlying cardiac arrhythmogenesis in diabetes mellitus J Diabetes Res 201620161
10 Koektuerk B Aksoy M Horlitz M Bozdag-Turan I Turan RG Role of diabetesin heart rhythm disorders World J Diabetes 2016745ndash9
11 Fox CS Coady S Sorlie PD Levy D Meigs JB DrsquoAgostino RB Sr et al Trends incardiovascular complications of diabetes JAMA 20042922495ndash9
12 Cho E Rimm EB Stampfer MJ Willett WC Hu FB The impact of diabetes mel-litus and prior myocardial infarction on mortality from all causes and from cor-onary heart disease in men J Am Coll Cardiol 200240954ndash60
13 Balkau B Jouven X Ducimetiere P Eschwege E Diabetes as a risk factor forsudden death Lancet 19993541968ndash9
14 Chamberlain AM Agarwal SK Folsom AR Soliman EZ Chambless LE Crow Ret al A clinical risk score for atrial fibrillation in a biracial prospective cohort(from the Atherosclerosis Risk in Communities [ARIC] study) Am J Cardiol201110785ndash91
15 Kannel WB Wolf PA Benjamin EJ Levy D Prevalence incidence prognosisand predisposing conditions for atrial fibrillation population-based estimatesAm J Cardiol 1998822Nndash9N
16 Dublin S Glazer NL Smith NL Psaty BM Lumley T Wiggins KL et al Diabetesmellitus glycemic control and risk of atrial fibrillation J Gen Intern Med 201025853ndash8
17 Fatemi O Yuriditsky E Tsioufis C Tsachris D Morgan T Basile J et al Impactof intensive glycemic control on the incidence of atrial fibrillation and associatedcardiovascular outcomes in patients with type 2 diabetes mellitus (from theAction to Control Cardiovascular Risk in Diabetes Study) Am J Cardiol 20141141217ndash22
18 Huxley RR Filion KB Konety S Alonso A Meta-analysis of cohort and case-control studies of type 2 diabetes mellitus and risk of atrial fibrillation Am JCardiol 201110856ndash62
19 Krahn AD Manfreda J Tate RB Mathewson FA Cuddy TE The natural historyof atrial fibrillation incidence risk factors and prognosis in the Manitobafollow-up study Am J Med 199598476ndash84
20 Watanabe H Tanabe N Watanabe T Darbar D Roden DM Sasaki S et alMetabolic syndrome and risk of development of atrial fibrillation the Niigatapreventive medicine study Circulation 20081171255ndash60
21 Schoen T Pradhan AD Albert CM Conen D Type 2 diabetes mellitus and riskof incident atrial fibrillation in women J Am Coll Cardiol 2012601421ndash8
22 Du X Ninomiya T de Galan B Abadir E Chalmers J Pillai A et al Risks of car-diovascular events and effects of routine blood pressure lowering among pa-tients with type 2 diabetes and atrial fibrillation results of the ADVANCEstudy Eur Heart J 2009301128ndash35
23 Aksnes TA Schmieder RE Kjeldsen SE Ghani S Hua TA Julius S Impact ofnew-onset diabetes mellitus on development of atrial fibrillation and heart fail-ure in high-risk hypertension (from the VALUE Trial) Am J Cardiol 2008101634ndash8
24 Gallagher C Hendriks JM Mahajan R Middeldorp ME Elliott AD Pathak RKet al Lifestyle management to prevent and treat atrial fibrillation Expert RevCardiovasc Ther 201614799ndash809
25 Nichols GA et al Independent contribution of diabetes to increased prevalenceand incidence of atrial fibrillation Diabetes Care 2009321851ndash6
26 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B et al 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78
27 Freedman B Camm J Calkins H Healey JS Rosenqvist M Wang J et alScreening for atrial fibrillation a report of the AF-SCREEN international collab-oration Circulation 20171351851ndash67
28 Mairesse GH Moran P Van Gelder I Elsner C Rosenqvist M Mant J et alScreening for Atrial Fibrillation a European Heart Rhythm Association (EHRA)consensus document endorsed by the Heart Rhythm Society (HRS) Asia PacificHeart Rhythm Society (APHRS) and Societad Latinoamericana de EstimulationCardiaca y Electrofisiologia (SOLAECE) Europace 2017191851ndash67
29 Zaccardi F Khan H Laukkanen JA Diabetes mellitus and risk of sudden cardiacdeath a systematic review and meta-analysis Int J Cardiol 2014177535ndash7
30 Anselmino M Matta M DrsquoAscenzo F Pappone C Santinelli V Bunch TJ et alCatheter ablation of atrial fibrillation in patients with diabetes mellitus a sys-tematic review and meta-analysis Europace 2015171518ndash25
31 Bogossian H Frommeyer G Brachmann J Lewalter T Hoffman E Kuck KHet al Catheter ablation of atrial fibrillation and atrial flutter in patients with dia-betes mellitus who benefits and who does not Data from German ablationregistry Int J Cardiol 201621425ndash30
32 Forleo GB Mantica M De Luca L Leo R Santini L Panigada S et al Catheterablation of atrial fibrillation in patients with diabetes mellitus type 2 resultsfrom a randomized study comparing pulmonary vein isolation versus antiar-rhythmic drug therapy J Cardiovasc Electrophysiol 20092022
33 Jouven X Lemaıtre RN Rea TD Sotoodehnia N Empana JP Siscovick DSDiabetes glucose level and risk of sudden cardiac death Eur Heart J 2005262142ndash7
34 Potpara T Marinkovic-Eric J Grujic M Radojkovic-Cirovic B Vujisic-Tesic BPetrovic M [Effect of diabetes mellitus in recovery and maintenance of sinusrhythm in patients with persistent atrial fibrillation] Srp Arh Celok Lek 2002130189ndash92
35 Kucharska-Newton AM Couper DJ Pankow JS Prineas RJ Rea TDSotoodehnia N et al Diabetes and the risk of sudden cardiac death theAtherosclerosis Risk in Communities study Acta Diabetol 201047(Suppl 1)161ndash8
36 Eranti A Kerola T Aro AL Tikkanen JT Rissanen HA Anttonen O et alDiabetes glucose tolerance and the risk of sudden cardiac death BMCCardiovasc Disord 20161651
37 Cardoso CR Salles GF Deccache W Prognostic value of QT interval param-eters in type 2 diabetes mellitus results of a long-term follow-up prospectivestudy J Diabetes Complications 200317169ndash78
38 Molon G Costa A Bertolini L Zenari L Arcaro G Barbieri E et al Relationshipbetween abnormal microvolt T-wave alternans and poor glycemic control intype 2 diabetic patients Pacing Clin Electrophysiol 2007301267ndash72
39 OrsquoBrien IA OrsquoHare JP Lewin IG Corrall RJ The prevalence of autonomic neur-opathy in insulin-dependent diabetes mellitus a controlled study based on heartrate variability Q J Med 198661957ndash67
40 Tsuji H Venditti FJ Jr Manders ES Evans JC Larson MG Feldman CL et alReduced heart rate variability and mortality risk in an elderly cohort TheFramingham Heart Study Circulation 199490878ndash83
41 Vinik AI Ziegler D Diabetic cardiovascular autonomic neuropathy Circulation2007115387ndash97
42 Singh JP Larson MG OrsquoDonnell CJ Wilson PF Tsuji H Lloyd-Jones DM et alAssociation of hyperglycemia with reduced heart rate variability (TheFramingham Heart Study) Am J Cardiol 200086309ndash12
43 Cherney DZ Perkins BA Soleymanlou N Har R Fagan N Johansen OE et alThe effect of empagliflozin on arterial stiffness and heart rate variability in sub-jects with uncomplicated type 1 diabetes mellitus Cardiovasc Diabetol 20141328
44 Balcıoglu S Arslan U Turkoglu S Ozdemir M Cengel A Heart rate variabilityand heart rate turbulence in patients with type 2 diabetes mellitus with versuswithout cardiac autonomic neuropathy Am J Cardiol 2007100890ndash3
45 Miwa Y Miyakoshi M Hoshida K Yanagisawa R Abe A Tsukada T et al Heartrate turbulence can predict cardiac mortality following myocardial infarction inpatients with diabetes mellitus J Cardiovasc Electrophysiol 2011221135ndash40
46 Bissinger A Ruxer J Ahmed RB Lubinski A Heart rate turbulence in patientswith poorly controlled diabetes mellitus type 2 Arch Med Sci 2014101073ndash7
EHRA position paper on arrhythmia management in endocrine disorders 25
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
47 Priori SG Blomstrom-Lundqvist C Mazzanti A Blom N Borggrefe M Camm Jet al 2015 ESC Guidelines for the management of patients with ventricular ar-rhythmias and the prevention of sudden cardiac death Europace 2015171601ndash87
48 Chen-Scarabelli C Scarabelli TM Suboptimal glycemic control independentlyof QT interval duration is associated with increased risk of ventricular arrhyth-mias in a high-risk population Pacing Clin Electrophysiol 2006299ndash14
49 Secrest AM Becker DJ Kelsey SF Laporte RE Orchard TJ Characterizingsudden death and dead-in-bed syndrome in Type 1 diabetes analysis fromtwo childhood-onset Type 1 diabetes registries Diabet Med 201128293ndash300
50 Tanenberg RJ Newton CA Drake AJ Confirmation of hypoglycemia in theldquodead-in-bedrdquo syndrome as captured by a retrospective continuous glucosemonitoring system Endocr Pract 201016244ndash8
51 NICE-SUGAR Study Investigators Finfer S Liu B Chittock DR Norton RMyburgh JA et al Hypoglycemia and risk of death in critically ill patients N EnglJ Med 20123671108ndash18
52 ORIGIN Trial Investigators Mellbin LG Ryden L Riddle MC Probstfield JRosenstock J et al Does hypoglycaemia increase the risk of cardiovascularevents A report from the ORIGIN trial Eur Heart J 2013343137ndash44
53 Gerstein HC Miller ME Genuth S Ismail-Beigi F Buse JB Goff DC Jr et alACCORD Study Group Long-term effects of intensive glucose lowering oncardiovascular outcomes N Engl J Med 2011364818ndash28
54 Gerstein HC Miller ME Byington RP Goff DC Jr Bigger JT Buse JB et alAction to Control Cardiovascular Risk in Diabetes Study Group Effects ofintensive glucose lowering in type 2 diabetes N Engl J Med 20083582545ndash59
55 Chow E Bernjak A Williams S Fawdry RA Hibbert S Freeman J et al Risk ofcardiac arrhythmias during hypoglycemia in patients with type 2 diabetes andcardiovascular risk Diabetes 2014631738ndash47
56 Hay LC Wilmshurst EG Fulcher G Unrecognized hypo- and hyperglycemia inwell-controlled patients with type 2 diabetes mellitus the results of continuousglucose monitoring Diabetes Technol Ther 2003519ndash26
57 Reno CM Daphna-Iken D Chen YS Vander Weele J Jethi K Fisher SJ Severehypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoa-drenal activation Diabetes 2013623570ndash81
58 Tsujimoto T Sugiyama T Shapiro MF Noda M Kajio H Risk of cardiovascularevents in patients with diabetes mellitus on beta-blockers Hypertension 201770103ndash10
59 Bangalore S Messerli FH Kostis JB Pepine CJ Cardiovascular protection usingbeta-blockers a critical review of the evidence J Am Coll Cardiol 200750563ndash72
60 American Diabetes A 6 Glycemic targets Diabetes Care 201740(Suppl 1)S48ndash56
61 Zinman B Wanner C Lachin JM Fitchett D Bluhmki E Hantel S et alEmpagliflozin cardiovascular outcomes and mortality in type 2 diabetes N EnglJ Med 20153732117ndash28
62 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JFE Nauck MAet al LEADER Steering Committee LEADER Trial Investigators Liraglutide andcardiovascular outcomes in type 2 diabetes N Engl J Med 2016375311ndash22
63 American Diabetes A 8 Pharmacologic approaches to glycemic treatmentDiabetes Care 201740(Suppl 1) S64ndash74
64 Mann JFE Oslashrsted DD Brown-Frandsen K Marso SP Poulter NR Rasmussen Set al Liraglutide and renal outcomes in type 2 diabetes N Engl J Med 2017377839ndash48
65 Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N et alCanagliflozin and cardiovascular and renal events in type 2 diabetes N Engl JMed 2017377644ndash57
66 Raz I Wiviott SD Multicenter trial to evaluate the effect of dapagliflozin on theincidence of cardiovascular events (DECLARE-TIMI58) ClinicalTrialsgovIdentifier NCT01730534
67 Sonesson C Johansson PA Johnsson E Gause-Nilsson I Cardovascular effectsof dapagliflozin in patients with type 2 diabetes and different risk categories ameta-analysis Cardiovasc Diabetol 20161537
68 Wu JHY Foote C Blomster J Toyama T Perkovic V Sundstrom J et al Effectsof sodium-glucose cotransporter-2 inhibitors on cardiovascular events deathand major safety outcomes in adults with type 2 diabetes a systematic reviewand meta-analysis Lancet Diabetes Endocrinol 20164411ndash9
69 Kalra S Sodium-glucose cotransporter 2 (SGLT2)inhibiotrs and cardiovasculardisease a systematic review Cardiol Ther 20165161ndash8
70 Holman RR Bethel MA Mentz RJ Thompson VP Lokhnygina Y Buse JB et alEffects of once-weekly exenatide on cardiovascular outcomes in type 2 dia-betes N Engl J Med 20173771228ndash39
71 Pfeffer MA Claggett B Diaz R Dickstein K Gerstein HC Kober LV et alLixisenatide in patients with type 2 diabetes and acute coronary syndrome NEngl J Med 20153732247ndash57
72 ADVANCE Collaborative Group Patel A MacMahon S Chalmers J Neal BBillot L et al Intensive blood glucose control and vascular outcomes in patientswith type 2 diabetes N Engl J Med 20083582560ndash72
73 Duckworth W Abraira C Moritz T Reda D Emanuele N Reaven PD et alGlucose control and vascular complications in veterans with type 2 diabetesN Engl J Med 2009360129ndash39
74 NICE-SUGAR Study Investigators Finfer S Chittock DR Su SY Blair D FosterD et al Intensive versus conventional glucose control in critically ill patientsN Engl J Med 20093601283ndash97
75 Chen YC Chen SA Chen YJ Chang MS Chan P Lin CI Effects of thyroid hor-mone on the arrhythmogenic activity of pulmonary vein cardiomyocytes J AmColl Cardiol 200239366ndash 7
76 Zhang Y Dedkov EI Lee B 3rd Li Y Pun K Gerdes AM Thyroid hormone re-placement therapy attenuates atrial remodeling and reduces atrial fibrillationinducibility in a rat myocardial infarction-heart failure model J Card Fail 2014201012ndash9
77 Mangiardi L Gaita F Brun S Presbitero P Nademanee K Singh BNAtrioventricular block complicating amiodarone-induced hypothyroidism in apatient with pre-excitation and rate-dependent bilateral bundle branch blockJ Am Coll Cardiol 19867180ndash4
78 Purtell K Roepke TK Abbot GW Cardiac arrhythmias and thyroid dysfunctiona novel genetic link Int J Biochem Cell Biol 2010421767ndash70
79 Galloway A Li H Vanderlinde-Wood M Khan M Benbrook A Liles C et alActivating autoantibodies to the b12-adrenergic and M2 muscarinic receptorsassociate with atrial tachyarrhythmias in patients with hyperthyroidismEndocrine 201549457ndash63
80 Selmer C Olesen JB Hansen ML Lindhardsen J Schjerning Olsen AMClausager J et al The spectrum of thyroid disease and risk of new onset atrialfibrillation a large population cohort study BMJ 2012345e7895
81 Frost L Vestergaard P Mosekilde L Hyperthyroidism and risk of atrial fibril-lation or flutter a population-based study Arch Intern Med 20041641675ndash8
82 Cappola AR Fried LP Arnold AM Danese MD Kuller LH Burke JL et alThyroid status cardiovascular risk and mortality in older adults JAMA 20062951033ndash41
83 Sawin CT Geller A Wolf PA Belanger AJ Baker E Bacharach P et al Lowserum thyrotropin concentrations as a risk factors for atrial fibrillation in olderpersons N Engl J Med 19943311249ndash52
84 Auer J Scheibner P Mische T Langsteger W Eber O Eber B Subclinicalhypothyroidism as a risk factor for atrial fibrillation Am Heart J 2001142838ndash42
85 Gammage MD Parle JV Holder RL Roberts LM Hobbs FDR Wilson S et alAssociation between free thyroxine concentration and atrial fibrillation ArchIntern Med 2007167928ndash34
86 Collet TH Gussekloo J Bauer DC den Elzen WPJ Wendy PJ Cappola ARet al MAS for the Thyroid Studies Collaboration Subclinical hyperthyroidismand the risk of coronary heart disease and mortality Arch Intern Med 2012172799ndash809
87 Heeringa J Hoogendoorn EH van der Deure WM Hofman A Peeters RP HopWCJ et al High-normal thyroid function and risk of atrial fibrillation Arch InternMed 20081682219ndash24
88 Floriani C Gencer B Collet TH Rodondi N Subclinical thyroid dysfunctionand cardiovascular diseases 2016 update Eur Heart J 2017 doi101093eurheartjehx050
89 Gorenek B Pelliccia A Benjamin EJ Boriani G Crijns HJ Fogel RI et alEuropean Heart Rhythm Association (EHRA)European Association ofCardiovascular Prevention and Rehabilitation (EACPR) position paper on howto prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) andAsia Pacific Heart Rhythm Society (APHRS) Europace 201719190ndash225
90 Kim EJ Lyass A Wang N Massaro JM Fox CS Benjamin EJ et al Relation ofhypothyroidism and incident atrial fibrillation (from the Framingham HeartStudy) Am Heart J 2014167123ndash6
91 Brandt F Thvilum M Almind D Christensen K Green A Hegedu L et alMorbidity before and after the diagnosis of hyperthyroidism a nationwideregister-based study PLoS One 20118e66711
92 Chauhan V Hypothyroidism was 300 more frequent that hyperthyroidismin patients with atrial fibrillation enrolled over 10 years Am J Med 2015128e51
93 Martinez-Comendador J Marcos-Vidal JM Gualis J Martin CE Marin E Otero Jet al Subclinical hypothyroidism might increase the risk of postoperative atrialfibrillation after aortic valve replacement Thorac Cardiovasc Surg 201664427ndash33
94 Jolobe OMP Thyroid heart disease should include the coincidental associationof hypothyroidism and atrial fibrillation Am J Med 2015128e9
26 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
95 Worku B Tortolani AJ Gulkarov I Isom OW Klein I Preoperative hypothy-roidism is a risk factor for postoperative atrial fibrillation in cardiac surgical pa-tients J Card Surg 201530307ndash12
96 Zhang Y Dedkov EI Teplitsky D Weltman NY Pol CJ Rajagopalan V et alBoth hypothyroidism and hyperthyroidism increase atrial fibrillation inducibilityin rats Circ Arrhythm Electrophysiol 20136952ndash9
97 Kolettis TM Tsatsoulis A Subclinical hypothyroidism an overlooked cause ofatrial fibrillation J Atr Fibrillation 20125710
98 Nakazawa HK Sakurai K Hamada N Momotani N Ito K Management of atrialfibrillation in the post-thyrotoxic state Am J Med 198272903ndash6
99 Zhou ZH Ma LL Wang LX Risk factors for persistent atrial fibrillation follow-ing successful hyperthyroidism treatment with radioiodine therapy Intern Med2011502947ndash51
100 Tsymbaliuk I Unukovych D Shvets N Dinets A Cardiovascular complicationssecondary to Gravesrsquo disease a prospective study from Ukraine PLoS One201510e0122388
101 Gauthier JM Mohamed HE Noureldine SI Nazari-Shafti TZ Thethi TK KandilE Impact of thyroidectomy on cardiac manifestations of Gravesrsquo diseaseLaryngoscope 20161261256ndash9
102 Feely J Peden N Use of beta-adrenoreceptor blocking drugs in hyperthyroid-ism Drugs 198427425ndash46
103 Jansson S Lie-Karlsen K Stenqvist O Korner U Lundholm K Tisell LE Oxygenconsumption in patients with hyperthyroidism before and after treatment withbeta-blockade vs thyrostatic treatment a prospective randomized study AnnSurg 200123360ndash4
104 Dalan R Leow MK Leow MC Leow M Cardiovascular collapse associatedwith beta-blockade in thyroid storm Exp Clin Endocrinol Diabetes 2007115392ndash6
105 Nakazawa HK Handa S Nakamura Y Oyanagi H Hasegawa M Ishikawa Net al High maintenance rate of sinus rhythm after cardioversion in post-thyrotoxic chronic atria1 fibrillation Int J Cardiol 19871647ndash55
106 Nakazawa H Lythall DA Noh J Ishikawa N Sugino K Ito K et al Is there aplace for the late cardioversion of atrial fibrillation A long-term follow-up studyof patients with post-thyrotoxic atrial fibrillation Eur Heart J 200021327ndash33
107 Siu C-W Jim M-H Zhang X Chan Y-H Pong V Kwok J et al Comparison ofatrial fibrillation recurrence rates after successful electrical cardioversion in pa-tients with hyperthyroidism-induced versus non-hyperthyroidism-induced per-sistent atrial fibrillation Am J Cardiol 2009103540ndash3
108 Ma CS Liu X Hu FL Dong JZ Liu XP Wang XH Catheter ablation of atrial fib-rillation in patients with hyperthyroidism J Interv Card Electrophysiol 200718137ndash42
109 Machino T Tada H Sekiguchi Y Yamasaki H Kuroki K Igarashi M Prevalenceand influence of hyperthyroidism on the long-term outcome of catheter abla-tion for drug-refractory atrial fibrillation Circ J 2012762546ndash51
110 Wongcharoen W Lin YJ Chang SL Lo LW Hu YF Chung FP History ofhyperthyroidism and long-term outcome of catheter ablation of drug-refractoryatrial fibrillation Heart Rhythm 2015121956ndash62
111 Chan PH Hai J Yeung CY Lip GY Lam KS Tse HF et al Benefit of anticoagula-tion therapy in hyperthyroidism-related atrial fibrillation Clin Cardiol 201538476ndash82
112 Friberg L Rosenqvist M Lip GY Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation theSwedish Atrial Fibrillation cohort study Eur Heart J 2012331500ndash10
113 Petersen P Hansen JM Stroke in thyrotoxicosis with atrial fibrillation Stroke19881915ndash8
114 Bruere H Fauchier L Bernard Brunet A Pierre B Simeon E Babuty D et alHistory of thyroid disorders in relation to clinical outcomes in atrial fibrillationAm J Med 201512830ndash7
115 von Olshausen K Bischoff S Kahaly G Mohr-Kahaly S Erbel R Beyer J et alCardiac arrhythmias and heart rate in hyperthyroidism Am J Cardiol 198963930ndash3
116 Kulairi Z Deol N Tolly R Manocha R Naseer M QT prolongation due toGravesrsquo disease Case Rep Cardiol 201720171
117 Kobayashi H Haketa A Abe M Tahira K Hatanaka Y Tanaka S et al Unusualmanifestation of Gravesrsquo disease ventricular fibrillation Eur Thyroid J 20154207ndash12
118 Ozcan KS Osmonov D Erdinler I Altay S Yildirim E Turkkan C et alAtrioventricular block in patients with thyroid dysfunction prognosis aftertreatment with hormone supplementation or antithyroid medication J Cardiol201260327ndash32
119 Namura M Kanaya H Lkeda M Shibayama S Ohka T Hyperthyroidism compli-cated with sick sinus syndrome Jpn Circ J 199559824ndash8
120 Kannan L Kotus-Bart J Amanullah A Prevalence of cardiac arrhythmias inhypothyroid and euthyroid patients Horm Metab Res 201749430ndash3
121 Lim CH Lim P Recurrent ventricular tachycardia in hypothyroidism Aust N Z JMed 1976668ndash70
122 Fredlund BO Olsson SB Long QT interval and ventricular tachycardia of ldquotor-sade de pointerdquo type in hypothyroidism Acta Med Scand 1983213231ndash5
123 Kukla P Szczuka K Słowiak-Lewinska T Bromblik A Hajduk B Kluczewski MAcquired long QT syndrome with torsade de pointes in a patient with primaryhypothyroidism Kardiol Pol 200358224ndash6
124 Schenck JB Rizvi AA Lin T Severe primary hypothyroidism manifesting withtorsades de pointes Am J Med Sci 2006331154ndash6
125 Kandan SR Saha M Severe primary hypothyroidism presenting with torsadesde pointes BMJ Case Rep 20122012bcr1220115306 doi 101136bcr1220115306
126 Ellis CR Murray KT When an ICD is not the answer Hypothyroidism-induced cardiomyopathy and torsades de pointes J Cardiovasc Electrophysiol2008191105ndash7
127 Rosengarten M Brooks R Torsade de pointes ventricular tachycardia in a hypo-thyroid patient treated with propafenone Can J Cardiol 19873234ndash9
128 Pedersen CT Kay GN Kalman J Borggrefe M Della-Bella P Dickfeld T et alEHRAHRSAPHRS expert consensus on ventricular arrhythmias Europace2014161257ndash83
129 Esposito F Liguori V Maresca G Cerrone A De Filippo O Trimarco B et alSubclinical hypothyroidism a reversible cause of complete loss of ventricularlead capture Circ Arrhythm Electrophysiol 20147182ndash4
130 Schlesinger Z Rosenberg T Stryjer D Gilboa Y Exit block in myxedematreated effectively by thyroid hormone therapy Pacing Clin Electrophysiol 19803737ndash9
131 Patton KK Levy M Viswanathan M Atrial lead dysfunction an unusual featureof hypothyroidism Pacing Clin Electrophysiol 2008311650ndash2
132 Basu D Chatterjee K Unusually high pacemaker threshold in severe myx-edema Decrease with thyroid hormone therapy Chest 197670677ndash9
133 Lardoux H Cenac A Perlemuter L Bernheim R Hazard J Disorders of intra-cardiac conduction and hypothyroidism in adults A systematic study of 42cases Nouv Presse Med 197541859ndash62
134 Numata T Abe H Terao T Nakashima Y Possible involvement of hypothyroid-ism as a cause of lithium-indiced sinus node dysfunction Pacing ClinElectrophysiol 199922954ndash7
135 Blanco VM Moller I Castano G Casares G Reversible sick sinus syndrome andhypothyroidism due to lithium Med Clin (Barc) 2003120478ndash9
136 Schantz ET Dubbs AW Complete auriculoventricular block in myxedema withreversion to normal sinus rhythm on thyroid therapy Am Heart J 195141613ndash9
137 Chatzitomaris A Scheeler M Gotzmann M Koditz R Schildroth J Knyhala KMet al Second degree AV block and severely impaired contractility in cardiacmyxedema a case report Thyroid Res 201586
138 Seol SH Kim DI Park BM Kim DK Song PS Jin HY et al Complete atrioven-tricular block presenting with syncope caused by severe hypothyroidismCardiol Res 20123239ndash41
139 Schoenmakers N de Graaff WE Peters RH Hypothyroidism as the cause ofatrioventricular block in an elderly patient Neth Heart J 20081657ndash9
140 Nakayama Y Ohno M Yonemura S Uozumi H Kobayakawa N Fukushima Ket al A case of transient 2 1 atrioventricular block resolved by thyroxine sup-plementation for subclinical hypothyroidism Pacing Clin Electrophysiol 200629106ndash8
141 Brignole M Auricchio A Baron-Esquivias G Bordachar P Boriani G BreithardtOA et al 2013 ESC guidelines on cardiac pacing and cardiac resynchronizationtherapy the task force on cardiac pacing and resynchronization therapy of theEuropean Society of Cardiology (ESC) Developed in collaboration with theEuropean Heart Rhythm Association (EHRA) Europace 2013151070ndash118
142 Jabrocka-Hybel A Bednarczuk T Bartalena L Pach D Ruchała M Kaminski Get al Amiodarone and the thyroid Endokrynol Pol 201566176ndash96
143 Bogazzi F Bartalena L Martino E Approach to the patient with amiodarone-induced thyrotoxicosis J Clin Endocrinol Metab 2010952529ndash35
144 De Leo S Lee SY Braverman LE Hyperthyroidism Lancet 2016388906ndash18145 Vassallo P Trohman RC Prescribing amiodarone an evidence-based review of
clinical indications JAMA 20072981312ndash22146 Barbesino G Tomer Y Clinical Utility of TSH Receptor Antibodies J Clin
Endocrinol Metab 2013982247ndash55147 Ross DS Burch HB Cooper DS Greenlee MC Laurberg P Maia AL et al 2016
American Thyroid Association guidelines for diagnosis and management ofhyperthyroidism and other causes of thyrotoxicosis Thyroid 2016261343ndash421
148 Benjamens S Dullaart RPF Sluiter WJ Rienstra M van Gelder IC Links TP Theclinical value of regular thyroid function tests during amiodarone treatment EurJ Endocrinol 20171779ndash14
149 Piccini JP Berger JS OrsquoConnor CM Amiodarone for the prevention of suddencardiac death a meta-analysis of randomized controlled trials Eur Heart J 2009301245ndash53
150 Vorperian VR Havighurst TC Miller S January CR Adverse effects of low doseamiodarone a meta-analysis J Am Coll Cardiol 199730791ndash8
EHRA position paper on arrhythmia management in endocrine disorders 27
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
151 Batcher EL Tang XC Singh BN Singh SN Reda DJ Hershman JM SAFE-TInvestigators Thyroid function abnormalities during amiodarone therapy forpersistent atrial fibrillation Am J Med 2007120880ndash5
152 Ross IL Marshall D Okreglicki A Isaacs S Levitt NS Amiodarone-induced thy-roid dysfunction S Afr Med J 200595180ndash3
153 Ahmed S Van Gelder IC Wiesfeld AC Van Veldhuisen DJ Links TPDeterminants and outcome of amiodarone-associated thyroid dysfunction ClinEndocrinol (Oxf) 201175388ndash94
154 Lee CH Nam G-B Park H-G Kim HY Park K-M Kim J et al Effects of antiar-rhythmic drugs on inappropriate shocks in patients with implantable cardi-overter defibrillators Circ J 200872102ndash5
155 Kinoshita S Hayashi T Wada K Yamato M Kuwahara T Anzai T et al Risk fac-tors for amiodarone-induced thyroid dysfunction in Japan J Arrhythm 201632474ndash80
156 Shiga T Wakaumi M Matsuda N Shoda M Hagiwara N Sato K et alAmiodarone-induced thyroid dysfunction and ventricular tachyarrhythmias dur-ing long-term therapy in Japan Jpn Circ J 200165958ndash60
157 Pillarisetti J Vanga SR Lakkireddy D Amiodarone induced thyrotoxicosismdashfluctuating RVOT and LV scar VT J Atr Fibrillation 201357ndash9
158 Mun H-S Shen C Pak H-N Lee M-H Lin S-F Chen P-S et al Chronic amiodar-one therapy impairs the function of the superior sinoatrial node in patients withatrial fibrillation Circ J 2013772255ndash63
159 Cracana I Vasilcu TF Mardare A Alexa ID Marcu DT Severe amiodarone-induced bradycardia conceals sick sinus syndrome case report Rev Med ChirSoc Med Nat Iasi 2016120110ndash3
160 Essebag V Hadjis T Platt RW Pilote L Amiodarone and the risk of bradyar-rhythmia requiring permanent pacemaker in elderly patients with atrial fibrilla-tion and prior myocardial infarction J Am Coll Cardiol 200341249ndash54
161 Czarnywojtek A Plazinska MT Zgorzalewicz-Stachowiak M Wolinski KStangierski A Miechowicz I et al Dysfunction of the thyroid gland during amio-darone therapy a study of 297 cases Ther Clin Risk Manag 201612505ndash13
162 Hermida JS Tcheng E Jarry G Moullart V Arlot S Rey JL et al Radioiodine ab-lation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxi-cosis in patients with resistant tachyarrhythmias Europace 20046169ndash74
163 UK Guidelines for the Use of Thyroid Function Tests 2002 wwwbritish-thyorid-associationorg (15 December 2017 date last accessed)
164 Diederichsen SZ Darkner S Chen X Johannesen A Pehrson S Hansen J et alShort-term amiodarone treatment for atrial fibrillation after catheter ablationinduces a transient thyroid dysfunction results from the placebo-controlledrandomized AMIO-CAT trial Eur J Intern Med 20163336ndash41
165 Hudzik B Zubelewicz-Szkodzinska B Amiodarone-related thyroid dysfunctionIntern Emerg Med 20149829ndash39
166 Zelinka T Petrak O Turkova H Holaj R Strauch B Krsek M et al High inci-dence of cardiovascular complications in pheochromocytoma Horm Metab Res201244379ndash84
167 Prejbisz A Lenders JWM Eisenhofer G Januszewicz A Cardiovascular mani-festations of phaeochromocytoma J Hypertens 2011292049ndash60
168 Dabrowska B Pruszczyk P Dabrowski A Feltynowski T Wocial B JanuszewiczW Influence of alpha-adrenergic blockade on ventricular arrhythmias QTcinterval and heart rate variability in phaeochromocytoma J Hum Hypertens19959925ndash9
169 Traykov VB Kotirkov KI Petrov IS Pheochromocytoma presenting with bidir-ectional ventricular tachycardia Heart 201399509
170 Brouwers FM Eisenhofer G Lenders JWM Pacak K Emergencies caused bypheochromocytoma neuroblastoma or ganglioneuroma Endocrinol Metab ClinNorth Am 200635699ndash724
171 Galetta F Franzoni F Bernini G Poupak F Carpi A Cini G et al Cardiovascularcomplications in patients with pheochromocytoma a mini-review BiomedPharmacother 201064505ndash9
172 Manger WM Gifford RW Pheochromocytoma J Clin Hypertens (Greenwich)2002462ndash72
173 Tewari P Sikora R Hypertension and tachycardia during adrenal manipulationCan J Anaesth 199542417ndash9
174 Colao A Ferone D Marzullo P Lombardi G Systemic complications of acro-megaly epidemiology pathogenesis and management Endocr Rev 200425102ndash52
175 McCabe J Ayuk J Sherlock M Treatment factors that influence mortality in ac-romegaly Neuroendocrinology 201610366ndash74
176 Dekkers OM Biermasz NR Pereira AM Romijn JA Vandenbroucke JPMortality in acromegaly a metaanalysis J Clin Endocrinol Metab 20089361ndash7
177 Katznelson L Laws ER Melmed S Molitch ME Murad MH Utz A et alAcromegaly an endocrine society clinical practice guideline J Clin EndocrinolMetab 2014993933ndash51
178 Ritvonen E Loyttyniemi E Jaatinen P Ebeling T Moilanen L Nuutila P et alMortality in acromegaly a 20-year follow-up study Endocr Relat Cancer 201623469ndash80
179 Bihan H Espinosa C Valdes-Socin H Salenave S Young J Levasseur S et alLong-term outcome of patients with acromegaly and congestive heart failureJ Clin Endocrinol Metab 2004895308ndash13
180 dos Santos Silva CM Gottlieb I Volschan I Kasuki L Warszawski L BalariniLima GA et al Low frequency of cardiomyopathy using cardiac magnetic reson-ance imaging in an acromegaly contemporary cohort J Clin Endocrinol Metab20151004447ndash55
181 Herrmann BL Bruch C Saller B Ferdin S Dagres N Ose C et al Occurrenceof ventricular late potentials in patients with active acromegaly Clin Endocrinol(Oxf) 200155201ndash7
182 Lie JT Grossman SJ Pathology of the heart in acromegaly anatomic findings in27 autopsied patients Am Heart J 198010041ndash52
183 Frustaci A Chimenti C Setoguchi M Guerra S Corsello S Crea F et al Celldeath in acromegalic cardiomyopathy Circulation 1999991426ndash34
184 Rossi E Zuppi P Pennestri F Biasucci LM Lombardo A De Marinis L et alAcromegalic cardiomyopathy Left ventricular filling and hypertrophy in activeand surgically treated disease Chest 19921021204ndash8
185 Lombardi G Galdiero M Auriemma RS Pivonello R Colao A Acromegaly andthe cardiovascular system Neuroendocrinology 200683211ndash7
186 Clayton RN Cardiovascular function in acromegaly Endocr Rev 200324272ndash7187 Hayward RP Emanuel RW Nabarro JD Acromegalic heart disease influence of
treatment of the acromegaly on the heart Q J Med 19876241ndash58188 Kahaly G Olshausen KV Mohr-Kahaly S Erbel R Boor S Beyer J et al
Arrhythmia profile in acromegaly Eur Heart J 19921351ndash6189 Surawicz B Mangiardi ML Electrocardiogram in endocrine and metabolic dis-
orders Cardiovasc Clin 19778243ndash66190 Marin F Pico AM Martinez JG Domınguez JR Alfayate R Sogorb F Heart dis-
ease in acromegaly Study of 27 patients Med Clin (Barc) 1996107326ndash30191 Rodrigues EA Caruana MP Lahiri A Nabarro JD Jacobs HS Raftery EB
Subclinical cardiac dysfunction in acromegaly evidence for a specific disease ofheart muscle Br Heart J 198962185ndash94
192 Maffei P Martini C Milanesi A Corfini A Mioni R de Carlo E et al Late poten-tials and ventricular arrhythmias in acromegaly Int J Cardiol 2005104197ndash203
193 Matturri L Varesi C Nappo A Cuttin MS Rossi L Sudden cardiac death in ac-romegaly Anatomopathological observation of a case Minerva Med 199889287ndash91
194 Rossi L Thiene G Caragaro L Giordano R Lauro S Dysrhythmias and suddendeath in acromegalic heart disease A clinicopathologic study Chest 197772495ndash8
195 Doimo S Miani D Finato N Driussi M Sinagra G Livi U et al Acromegalic car-diomyopathy with malignant arrhythmogenic pattern successfully treated withmechanical circulatory support and heart transplantation Can J Cardiol 201733830 e9ndashe11
196 Unubol M Eryilmaz U Guney E Ture M Akgullu C QT dispersion in patientswith acromegaly Endocrine 201343419ndash23
197 Baser H Akar Bayram N Polat B Evranos B Ersoy R Bozkurt E et al Theevaluation of QT intervals during diagnosis and after follow-up in acromegalypatients Acta Med Port 201427428ndash32
198 Warszawski L Kasuki L Sa R Dos Santos Silva CM Volschan I Gottlieb I et alLow frequency of cardniac arrhythmias and lack of structural heart disease inmedically-naive acromegaly patients a prospective study at baseline and after 1year of somatostatin analogs treatment Pituitary 201619582ndash9
199 Lombardi G Colao A Marzullo P Biondi B Palmieri E Fazio S Improvement ofleft ventricular hypertrophy and arrhythmias after lanreotide-induced GH andIGF-I decrease in acromegaly A prospective multi-center study J EndocrinolInvest 200225971ndash6
200 Auriemma RS Pivonello R De Martino MC Cudemo G Grasso LF Galdiero Met al Treatment with GH receptor antagonist in acromegaly effect on cardiacarrhythmias Eur J Endocrinol 201216815ndash22
201 Mercado M Gonzalez B Vargas G Ramirez C de los Monteros AL Sosa Eet al Successful mortality reduction and control of comorbidities in patientswith acromegaly followed at a highly specialized multidisciplinary clinicJ Endocrinol Metab 2014994438ndash46
202 Horner JM Thorsson AV Hintz R Growth deceleration patterns in childrenwith constitutional short statue an aid to diagnosis Pediatrics 197862529ndash34
203 Ascoli P Cavagnini F Hypopituitarism Pituitary 20069335ndash42204 Simsek Y Kaya MG Tanriverdi F Calapkorur B Diri H Karaca Z et al
Evaluation of long-term pituitary functions in patients with severe ventriculararrhythmia a pilot study J Endocrinol Invest 2014371057ndash64
205 Okada T Tomoda T Shinohara M Misaki Y Shiraishi T Fujieda M et alAtrioventricular block in a patient with growth hormone deficiency duringgrowth hormone therapy Pediatr Int 19994190ndash3
206 Conn JW Knopf RF Nesbit RM Clinical characteristics of primary aldosteron-ism from an analysis of 145 cases Am J Surg 1964107159ndash72
28 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
207 Lim JS Park S Park SI Oh YT Choi E Kim JY et al Cardiac dysfunction in asso-ciation with increased inflammatory markers in primary aldosteronismEndocrinol Metab (Seoul) 201631567ndash76
208 Iravanian S Dudley SC Jr The renin-angiotensin-aldosterone system (RAAS)and cardiac arrhythmias Heart Rhythm 20085S12ndash7
209 Sechi LA Colussi G Di Fabio A Catena C Cardiovascular and renal damage inprimary aldosteronism outcomes after treatment Am J Hypertens 2010231253ndash60
210 Catena C Colussi G Nait F Martinis F Pezzutto F Sechi LA Aldosterone andthe heart still an unresolved issue Front Endocrinol (Lausanne) 20145168
211 Rhee SS Pearce EN Update systemic Diseases and the Cardiovascular System(II) The endocrine system and the heart a review Rev Esp Cardiol 201164220ndash31
212 Milliez P Girerd X Plouin PF Blacher J Safar ME Mourad JJ Evidence for anincreased rate of cardiovascular events in patients with primary aldosteronismJ Am Coll Cardiol 2005451243ndash8
213 Mihailidou AS Aldosterone in heart disease Curr Hypertens Rep 201214125ndash9214 He BJ Anderson ME Aldosterone and cardiovascular disease the heart of the
matter Trends Endocrinol Metab 20132421ndash30215 Stowasser M New perspectives on the role of aldosterone excess in cardiovas-
cular disease Clin Exp Pharmacol Physiol 200128783ndash91216 Weiss JN Qu Z Shivkumar K Electrophysiology of hypokalemia and hyperkale-
mia Circ Arrhythm Electrophysiol 201710e004667217 Seccia TM Caroccia B Adler GK Maiolino G Cesari M Rossi GP Arterial
hypertension atrial fibrillation and hyperaldosteronism the triple troubleHypertension 201769545ndash50
218 Zelinka T Holaj R Petrak O Strauch B Kasalicky M Hanus T et al Life-threatening arrhythmia caused by primary aldosteronism Med Sci Monit 200915CS174ndash7
219 Porodko M Auer J Eber B Connrsquos syndrome and atrial fibrillation Lancet 20013571293ndash4
220 Watson T Karthikeyan VJ Lip GY Beevers DG Atrial fibrillation in primary al-dosteronism J Renin Angiotensin Aldosterone Syst 200910190ndash4
221 Mulatero P Monticone S Bertello C Viola A Tizzani D Iannaccone A et alLong-term cardio- and cerebrovascular events in patients with primary aldos-teronism J Clin Endocrinol Metab 2013984826ndash33
222 Born-Frontsberg E Reincke M Rump LC Hahner S Diederich S Lorenz Ret al Cardiovascular and cerebrovascular comorbidities of hypokalemic andnormokalemic primary aldosteronism results of the German Connrsquos RegistryJ Clin Endocrinol Metab 2009941125ndash30
223 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ et al 2016ESC Guidelines for the diagnosis and treatment of acute and chronic heart fail-ure the Task Force for the diagnosis and treatment of acute and chronic heartfailure of the European Society of Cardiology (ESC) developed with the specialcontribution of the Heart Failure Association (HFA) of the ESC Eur Heart J2016372129ndash200
224 Sade E Oto A Oto A Oner Z Daver A Onalan O et al Adrenal adenomapresenting with torsade de pointesmdasha case report Angiology 200253471ndash4
225 Geist M Dorian P Davies T Greene M Newman D Hyperaldosteronism andsudden cardiac death Am J Cardiol 199678605ndash6
226 Aydin A Okmen E Erdinler I Sanli A Cam N Adrenal adenoma presentingwith ventricular fibrillation Tex Heart Inst J 20053285ndash7
227 Petramala L Savoriti C Zinnamosca L Marinelli C Settevendemmie A CalvieriC et al Primary aldosteronism with concurrent primary hyperparathyroidism ina patient with arrhythmic disorders Intern Med 2013522071ndash5
228 Catena C Colussi G Nadalini E Chiuch A Baroselli S Lapenna R et alCardiovascular outcomes in patients with primary aldosteronism after treat-ment Arch Intern Med 200816880ndash5
229 Savard S Amar L Plouin PF Steichen O Cardiovascular complications associ-ated with primary aldosteronism a controlled cross-sectional studyHypertension 201362331ndash6
230 Charmandari E Nicolaides NC Chrousos GP Adrenal insufficiency Lancet20143832152ndash67
231 Schumaecker MM Larsen TR Sane DC Cardiac manifestations of adrenal insuf-ficiency Rev Cardiovasc Med 201617131ndash6
232 Mozolevska V Schwartz A Cheung D Shaikh B Bhagirath KM Jassal DSAddisonrsquos disease and dilated cardiomyopathy a case report and review of theliterature Case Rep Cardiol 201620161
233 Fallo F Betterle C Budano S Lupia M Boscaro M Sonino N Regression of car-diac abnormalities after replacement therapy in Addisonrsquos disease Eur JEndocrinol 1999140425ndash8
234 Ikegami Y Fukuda T Jo R Momiyama Y Reversible cardiomyopathy accompa-nied by secondary adrenal insufficiency Circ Heart Fail 20169e002919
235 Singh G Manickam A Sethuraman M Rathod RC Takotsubo cardiomyopathyin a patient with pituitary adenoma and secondary adrenal insufficiency Indian JCrit Care Med 201519731ndash4
236 Somerville W The effect of cortisone on the cardiogram in chronic adrenal in-sufficiency Br Med J 19502860ndash2
237 Nishizawa S Nakamura T Hamaoka T Matsumuro A Sawada T Matsubara HLethal arrhythmia and corticosteroid insufficiency Am J Emerg Med 2009271167 e1ndash3
238 Kanamori K Yamashita R Tsutsui K Hara M Murakawa Y Long QT syndromeassociated with adrenal insufficiency in a patient with isolated adrenocortico-tropic hormone deficiency Intern Med 2014532329ndash31
239 Ozcan F Ustun I Berker D Aydin Y Delibasi T Guler S Inverted T waves inpatient with Addisonian crisis J Natl Med Assoc 2005971539ndash40
240 Dogan M Ertem AG Cimen T Yeter E Type-1 Brugada-like ECG patterninduced by adrenal crisis Herz 201540304ndash6
241 Komuro J Kaneko M Ueda K Nitta S Kasao M Shirai T Adrenal insufficiencycauses life-threatening arrhythmia with prolongation of QT interval HeartVessels 2016311003ndash5
242 Rentoukas E Lazaros G Sotiriou S Athanassiou M Tsiachris D Deftereos Set al Extreme but not life-threatening QT interval prolongation Take a closerlook at the neck J Electrocardiol 201346128ndash30
243 Cakerri L Husi G Minxuri D Roko E Vyshka G Primary hypoparathyroidismpresenting with heart failure and ventricular fibrillation Oxf Med Case Reports2014201477ndash9
244 Lind L Ljunghall S Serum calcium and the ECG in patients with primary hyper-parathyroidism J Electrocardiol 19942799ndash103
245 Voss DM Drake EH Cardiac manifestations of hyperparathyroidism with pres-entation of a previously unreported arrhythmia Am Heart J 196773235ndash9
246 Chadli MC Chaieb L Jemni L Chatti N Allegue M Zebidi A et al Bigeminal ar-rhythmia associated with hyperparathyroid crisis Cmaj 19881381115ndash6
247 Chang CJ Chen SA Tai CT Yu WC Chen YJ Tsai CF et al Ventricular tachy-cardia in a patient with primary hyperparathyroidism Pacing Clin Electrophysiol200023534ndash7
248 Kolb C Lehmann G Schreieck J Ndrepepa G Schmitt C Storms of ventriculartachyarrhythmias associated with primary hyperparathyroidism in a patient withdilated cardiomyopathy Int J Cardiol 200387115ndash6
249 Vestergaard P Mollerup CL Froslashkjaer VG Christiansen P Blichert-Toft MMosekilde L Cardiovascular events before and after surgery for primary hyper-parathyroidism World J Surg 200327216ndash22
250 Hedback G Oden A Tisell LE The influence of surgery on the risk of death inpatients with primary hyperparathyroidism World J Surg 199115399ndash405
251 Pepe J Curione M Morelli S Varrenti M Cammarota C Cilli M et alParathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidismas evaluated by exercise test Eur J Endocrinol 2013169255ndash61
252 Speakman MT Kloner RA Viagra and cardiovascular disease CardiovascPharmacol Therapeut 19994269ndash71
253 Occhetta E Bortnik M Magnani A Francalacci G Vassanelli C Primary hyper-parathyroidism and arrhythmic storm in a patient with an implantable cardi-overter defibrillator for primary prevention of sudden death Europace 20046184ndash8
254 Di Fusco SA Palazzo S Colivicchi F Santini M World Society of ArrhythmiasThe influence of gender on heart rhythm disease Pacing Clin Electrophysiol 201437650ndash7
255 Tadros R Ton AT Fiset C Nattel S Sex differences in cardiac electrophysi-ology and clinical arrhythmias epidemiology therapeutics and mechanisms CanJ Cardiol 201430783ndash92
256 Curtis AB Narasimha D Arrhythmias in women Clin Cardiol 201235166ndash71257 Jonsson MK Vos MA Duker G Demolombe S van Veen TA Gender disparity
in cardiac electrophysiology implications for cardiac safety pharmacologyPharmacol Ther 20101279ndash18
258 Gaborit N Varro A Le Bouter S Szuts V Escande D Nattel S et al Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts J Mol Cell Cardiol 201049639ndash46
259 Surawicz B Parikh SR Prevalence of male and female patterns of early ventricu-lar repolarization in the normal ECG of males and females from childhood toold age J Am Coll Cardiol 2002401870ndash6
260 Makkar RR Fromm BS Steinman RT Meissner MD Lehmann MH Female gen-der as a risk factor for torsades de pointes associated with cardiovascular drugsJAMA 19932702590 7
261 Tisdale JE Jaynes HA Overholser BR Sowinski KM Flockhart DA Kovacs RJInfluence of oral progesterone administration on drug-induced qt intervallengthening a randomized double-blind placebo-controlled crossover studyJACC Clin Electrophysiol 20162765ndash74
262 Locati EH Zareba W Moss AJ Schwartz PJ Vincent GM Lehmann MH et alAge- and sex-related differences in clinical manifestations in patients with con-genital long-QT syndrome findings from the International LQTS RegistryCirculation 1998972237ndash44
263 Seth R Moss AJ McNitt S Zareba W Andrews ML Qi M et al Long QT syn-drome and pregnancy J Am Coll Cardiol 2007491092ndash8
EHRA position paper on arrhythmia management in endocrine disorders 29
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
Downloaded from httpsacademicoupcomeuropaceadvance-article-abstractdoi101093europaceeuy0514939247by kutuphane useron 03 April 2018
264 Rodriguez L-M de Chillou C Schlapfer J Metzger J Baiyan X van den Dool Aet al Age at onset and gender of patients with different types of supraventricu-lar tachycardias Am J Cardiol 1992701213ndash5
265 Silversides CK Harris L Haberer K Sermer M Colman JM Siu SC Recurrencerates of arrhythmias during pregnancy in women with previous tachyarrhythmiaand impact on fetal and neonatal outcomes Am J Cardiol 2006971206ndash12
266 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratifi-cation for predicting stroke and thromboembolism in atrial fibrillation using anovel risk factor-based approach the Euro Heart survey on atrial fibrillationChest 2010137263ndash72
267 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in pa-tients with atrial fibrillation Chest 20101381093ndash100
268 Pisters R Lane DA Marin F Camm AJ Lip GY Stroke and thromboembolismin atrial fibrillation Circ J 2012762289ndash304
269 Overvad TF Skjoth F Lip GY Lane DA Albertsen IE Rasmussen LH et alDuration of diabetes mellitus and risk of thromboembolism and bleeding inatrial fibrillation nationwide cohort study Stroke 2015462168ndash74
270 Ashburner JM Go AS Chang Y Fang MC Fredman L Applebaum KM et alEffect of diabetes and glycemic control on ischemic stroke risk in AF patientsaTRIA study J Am Coll Cardiol 201667239ndash47
271 Lip GY Clementy N Pierre B Boyer M Fauchier L The impact of associateddiabetic retinopathy on stroke and severe bleeding risk in diabetic patients withatrial fibrillation the Loire Valley atrial fibrillation project Chest 20151471103ndash10
272 Lega JC Bertoletti L Gremillet C Chapelle C Mismetti P Cucherat M et alConsistency of safety and efficacy of new oral anticoagulants across subgroupsof patients with atrial fibrillation PLoS One 20149be91398
273 Apostolakis S Sullivan RM Olshansky B Lip GY Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin theSAMe-TT(2)R(2) score Chest 20131441555ndash63
274 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrialfibrillation past present and future Comparing the guidelines and practical de-cision-making Thromb Haemost 20171171230ndash9
275 Tang RB Liu DL Dong JZ Liu XP Long DY Yu RH et al High-normal thyroidfunction and risk of recurrence of atrial fibrillation after catheter ablation Circ J2010741316ndash21
276 Sousa PA Providencia R Albenque JP Khoueiry Z Combes N Combes S et alImpact of free thyroxine on the outcomes of left atrial ablation procedures AmJ Cardiol 20151161863ndash8
277 Kim KH Mohanty S Mohanty P Trivedi C Morris EH Santangeli P et alPrevalence of right atrial non-pulmonary vein triggers in atrial fibrillation pa-tients treated with thyroid hormone replacement therapy J Interv CardElectrophysiol 201749111ndash7
278 Wang M Cai S Sun L Zhao Q Feng W Safety and efficacy of early radiofre-quency catheter ablation in patients with paroxysmal atrial fibrillation compli-cated with amiodarone-induced thyrotoxicosis Cardiol J 201623416ndash21
279 Mikhaylov EN Orshanskaya VS Lebedev AD Szili-Torok T Lebedev DSCatheter ablation of paroxysmal atrial fibrillation in patients with previousamiodarone-induced hyperthyroidism a case-control study J CardiovascElectrophysiol 201324888ndash93
280 Diemberger I Biffi M Martignani C Boriani G From lead management to im-planted patient management indications to lead extraction in pacemaker andcardioverter-defibrillator systems Expert Rev Med Devices 20118235ndash55
281 Mazzotti A Biffi M Massaro G Martignani C Ziacchi M Bacchi Reggiani MLet al From lead management to implanted patient management systematic re-view and meta-analysis of the last 15 years of experience in lead extractionExpert Rev Med Devices 201310551ndash73
282 Habib A Le KY Baddour LM Friedman PA Hayes DL Lohse CM et al MayoCardiovascular Infections Study Group Predictors of mortality in patients withcardiovascular implantable electronic device infections Am J Cardiol 2013111874ndash9
283 De Maria E Diemberger I Vassallo PL Pastore M Giannotti F Ronconi C et alPrevention of infections in cardiovascular implantable electronic devices beyondthe antibiotic agent J Cardiovasc Med (Hagerstown) 201415554ndash64
284 Nielsen JC Gerdes JC Varma N Infected cardiac-implantable electronic de-vices prevention diagnosis and treatment Eur Heart J 2015362484ndash90
285 Charlson ME Pompei P Ales KL MacKenzie CR A new method of classifying-prognostic comorbidity in longitudinal studies development and validationJ Chronic Dis 198740373ndash83
286 Boriani G Berti E Belotti LM Biffi M De Palma R Malavasi VL et al RERAI(Registry of Emilia Romagna on Arrhythmia Interventions) InvestigatorsCardiac device therapy in patients with left ventricular dysfunction and heartfailure 0real-world0 data on long-term outcomes (mortality hospitalizationsdays alive and out of hospital) Eur J Heart Fail 201618693ndash702
287 Echouffo-Tcheugui JB Masoudi FA Bao H Spatz ES Fonarow GC Diabetesand outcomes of cardiac resynchronization with implantable cardioverter defib-rillator therapy in older patients with heart failure Circ Arrhythm Electrophysiol20169e004132
288 Boriani G The impact of diabetes and comorbidities on the outcome of heartfailure patients treated with cardiac resynchronization therapy implications forpatient management Circ Arrhythm Electrophysiol 20169e004463
289 Sun H Guan Y Wang L Zhao Y Lv H Bi X et al Influence of diabetes on car-diac resynchronization therapy in heart failure patients a meta-analysis BMCCardiovasc Disord 20151525
290 Hoppe UC Freemantle N Cleland JG Marijianowski M Erdmann E Effect ofcardiac resynchronization on morbidity and mortality of diabetic patients withsevere heart failure Diabetes Care 200730722ndash4
291 Earley A Persson R Garlitski AC Balk EM Uhlig K Effectiveness of implantablecardioverter-defibrillators for primary prevention of sudden cardiac death insubgroups a systematic review Ann Intern Med 2014160111-121
292 Shahreyar M Mupiddi V Choudhuri I Sra J Tajik AJ Jahangir A Implantable car-dioverter defibrillators in diabetics efficacy and safety in patients at risk of sud-den cardiac death Expert Rev Cardiovasc Ther 201513897ndash906
293 Braunschweig F Boriani G Bauer A Hatala R Herrmann-Lingen C Kautzner Jet al Management of patients receiving implantable cardiac defibrillator shocksrecommendations for acute and long-term patient management Europace 2010121673ndash90
294 Boriani G Savelieva I Dan GA Deharo JC Ferro C Israel CW et al Chronickidney disease in patients with cardiac rhythm disturbances or implantable elec-trical devices clinical significance and implications for decision making-a positionpaper of the European Heart Rhythm Association endorsed by the HeartRhythm Society and the Asia Pacific Heart Rhythm Society Europace 2015171169ndash96
295 Roffi M Cattaneo F Brandle M Thyrotoxicosis and the cardiovascular systemMinerva Endocrinol 20053047ndash58
296 Marketou ME Simantirakis EN Manios EG Vardas PE Electrical storm due toamiodarone induced thyrotoxicosis in a young adult with dilated cardiomyop-athy thyroidectomy as the treatment of choice Pacing Clin Electrophysiol 2001241827ndash8
297 Sharma AK Vegh EM Orencole M Miller A Blendea D Moore S et alAssociation of hypothyroidism with adverse events in patients with heart failurereceiving cardiac resynchronization therapy Am J Cardiol 20151151249ndash53
298 Chen S Shauer A Zwas DR Lotan C Keren A Gotsman I The effect of thy-roid function on clinical outcome in patients with heart failure Eur J Heart Fail201416217ndash26
299 Study of the effects of intravenous exenatide on cardiac repolarizationClinicalTrialsgov Identifier NCT 02650479
300 Haugaard SB Sajadeh A The Effect of liraglutide on the treatment of coronaryartery disease and type 2 diabetes (AddHope2) ClinicalTrialsgov IdentifierNCT 01595789
301 Rosenqvist M Giesecke P Thumb-ECG ambulant screening for atrial fibrillationin patients treated for hyperthyroidism (TAMBOURINE) (TAMBOURINE)ClinicalTrialsgov Identifier NCT 01945229
302 Giesecke P Is a Low Thyreotropin level predictive of recurrent arrhythmiaafter catheter ablative surgery (TABLAS) ClinicalTrialsgov Identifier NCT01789541
303 Kerstens MN Links TP Wietasch GJ Phenoxybenzamine versus doxazosin inPCC patients (PRESCRIPT) ClinicalTrialsgov Identifier NCT 01379898
304 Zhang B Assessment of BIM23B065 given as repeated subcutaneous injectionin subjects with acromegaly (DOPAACRO 002) ClinicalTrialsgov IdentifierNCT03045302
30 B Gorenek et al
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