Evaluation of Early Complications Relatedto De Novo Cardioverter Defibrillator ImplantationInsights From the Ontario ICD Database
Douglas S. Lee, MD, PHD,*† Andrew D. Krahn, MD,¶ Jeffrey S. Healey, MD, MSC,�David Birnie, MBCHB,# Eugene Crystal, MD,‡ Paul Dorian, MD,§ Christopher S. Simpson, MD,**Yaariv Khaykin, MD,†† Douglas Cameron, MD,† Amir Janmohamed, MD,‡‡ Raymond Yee, MD,¶Peter C. Austin, PHD,* Zhongliang Chen, MD, MSC,* Judy Hardy, RN,* Jack V. Tu, MD, PHD,*‡for the Investigators of the Ontario ICD Database
Toronto, Hamilton, London, Ottawa, Kingston, Newmarket, and Scarborough, Ontario, Canada
Objectives This study examined the predictors of early complications after defibrillator implantation.
Background Although implantable cardioverter-defibrillators are widely used, predictors of procedural complications and theconsequences of these events have not been determined.
Methods In a prospective, multicenter, population-based clinical outcomes registry of all newly implanted defibrillator pa-tients at 18 centers in Ontario, Canada, we examined 45-day complications and all-cause mortality from Febru-ary 2007 to May 2009. Complications were determined longitudinally and were categorized as direct implant-related or indirect events.
Results Among 3,340 patients (mean age 63.8 � 12.5 years, 78.5% men), major complications occurred in 4.1% ofde novo procedures. Compared with those undergoing a single-chamber device, implantation of a cardiacresynchronization defibrillator (adjusted hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.38 to 3.43,p � 0.001) or dual-chamber device (adjusted HR: 1.82, 95% CI: 1.19 to 2.79, p � 0.006) was associated withincreased risk of major complications. Major complications were increased in women (adjusted HR: 1.49, 95%CI: 1.02 to 2.16, p � 0.037) and when left ventricular end-systolic dimension exceeded 45 mm (adjusted HR:1.54, 95% CI: 1.08 to 2.20, p � 0.018). Major complications (excluding death) occurring early after defibrillatorimplantation were associated with increased adjusted risk of subsequent death up to 180 days after defibrillatorimplant (adjusted HR: 3.70, 95% CI: 1.64 to 8.33, p � 0.002). Direct implant-related complications were associ-ated with increased risk of early death (adjusted HR: 24.89, p � 0.01), whereas indirect clinical complicationsconferred increased risk of near-term death (adjusted HR: 12.35, p � 0.001) after defibrillator implantation.
ublished by Elsevier Inc. doi:10.1016/j.jacc.2009.11.029
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udden cardiac events due to ventricular tachyarrhythmiare important causes of premature death. Implantable
rom the *Institute for Clinical Evaluative Sciences, †Toronto General Hospital,Sunnybrook Health Sciences Centre, and §St. Michael’s Hospital, Toronto, On-ario, Canada; �Hamilton Health Sciences Centre, Hamilton, Ontario, Canada;London Health Sciences Centre, London, Ontario, Canada; #University of Ottawaeart Institute, Ottawa, Ontario, Canada; **Kingston General Hospital, Kingston,ntario, Canada; ††Southlake Regional Health Centre, Newmarket, Ontario,anada; and the ‡‡Rouge Valley Health System, Scarborough, Ontario, Canada. The
nstitute for Clinical Evaluative Sciences (ICES) is supported in part by a grant fromhe Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions,esults and conclusions are those of the authors and no endorsement by the
OHLTC or by the ICES is intended or should be inferred. This research wasupported by a grant from the MOHLTC, a Canadian Institutes of Health Research 2
ardioverter-defibrillators (ICDs) have been found to reducehe risk of arrhythmic death and total mortality in patients with
CIHR) clinician-scientist award (to Dr. Lee), a Career Investigator award from theeart and Stroke Foundation of Ontario (to Dr. Austin), and a Canada Researchhair in Health Services Research (to Dr. Tu). Dr. Krahn has received research
unding and is a consultant to Boston Scientific. Dr. Healey has received researchunding from Boston Scientific. Dr. Birnie is a consultant to Medtronic andarticipates in clinical trials sponsored by Medtronic, Boston Scientific, and St. Judeedical. Dr. Crystal has received educational grants from Medtronic, Boston
cientific, and St. Jude. Dr. Simpson has received speaker’s fees from Medtronic. Dr.haykin has received honoraria and speaker’s fees for St. Jude Medical andedtronic. Dr. Yee is a consultant for and on the Speakers’ Bureau of Medtronic.
Manuscript received September 12, 2009; revised manuscript received November 9,
009, accepted November 18, 2009.
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775JACC Vol. 55, No. 8, 2010 Lee et al.February 23, 2010:774–82 Complications of ICDs
eft ventricular systolic dysfunction and selected patients withrior cardiac arrest or sustained ventricular tachycardia (1–4).n response to the broadening indication for these devices, these of ICDs has increased to include patients who are asymp-omatic but could be at increased risk of sudden cardiac death.
Implantation of a cardioverter-defibrillator entails a surgicalrocedure with the attendant potential for complications.ittle is known about the rates and predictors of complicationsfter ICD implantation. Indeed, patients who undergo defi-rillator implantation have significant cardiac conditions andoncardiac comorbidities and may therefore be at higher risk ofeveloping complications from the procedure than has beenemonstrated in randomized trials (5). Furthermore, the typesf devices being used currently also differ from those used inhe clinical trials, with greater use of dual-chamber devices orardiac resynchronization defibrillators. Complications of ICDmplantation are not only important from the standpoint ofatient care, but they also add significantly to length of hospitaltay, increase health care costs, and influence the defibrillator’sost-effectiveness (6).
In this study, we examined the outcomes of patientsndergoing defibrillator implantation in the Ontario ICDatabase, a population-based, prospective registry of pa-
ients undergoing device implantation. In de novo defibril-ator recipients undergoing the procedure for primary orecondary prevention, we examined the frequency of thesearly complications and their predictors. We hypothesizedhat the burden of complications after defibrillator implan-ation would be predicted by both patient and deviceharacteristics.
ethods
atients. We examined patients undergoing de novo implan-ation of a cardioverter defibrillator (e.g., for primary orecondary prevention indication) in the Ontario ICD Databaseetween February 2007 and May 2009. The design andethodology of the Ontario ICD Database have been pub-
ished elsewhere (7). Briefly, this project is an ongoing pro-pective clinical registry of all patients (age �16 years) under-oing defibrillator implantation in Ontario, Canada, which haseen mandated by the Ontario Ministry of Health andong-Term Care. Patient data are collected upon initialvaluation, at the time of defibrillator implant, and at eachollow-up visit in the device clinic. As a prescribed entity, weere able to collect data on all patients in this registry without
nformed consent, and therefore all patients had their datantered into the database without participation bias (8).
ata sources. Details of the primary data collection processor the Ontario ICD Database have been described previously7). Briefly, data in the ICD database were collected by thelectrophysiologist and a trained research coordinator at defi-rillator implantation centers, who entered the data into aecure, firewall- and password-protected Web-based registry athe Institute for Clinical Evaluative Sciences. We collected
ata on patient characteristics, indication for the defibrillator, o
omorbidities, left ventricular ejec-ion fraction, and implant-relatedata. We also collected clinical andevice-related events occurring inollow-up, with data entered at themplanting hospital or peripheralmbulatory device clinics. Datauality was continually assessed by:) regular review and correspon-ence with study sites to ensureccuracy of coded data; 2) auto-ated range checks, notification to study sites of uncoded data
lements followed by recoding; 3) logic checks of key datalements including dates of all events; and 4) ongoing randomite audits for reliability and data collection mechanisms.
Deaths were identified by clinical follow-up at routineefibrillator clinic visits and via the Registered Personsatabase linked using the patient’s unique encrypted health
ard number. Vital status data were available for all studyatients. Ethics approval was obtained from the Sunny-rook Health Sciences Centre before study initiation. Aomplete list of participating defibrillator implant andollow-up sites is shown in Online Appendix 1.
omplications. At defibrillator clinic visits after devicemplantation, patients were routinely evaluated for anyevice-related complications that occurred within 45 days ofhe procedure using a standard checklist. We selected 45ays for determination of complications for several reasons:) it was temporally close to the device implant date; 2) allites conducted an initial post-implant clinic visit within 45ays; and 3) most early complications occurred during thiseriod, thus maximizing the potential capture of events (9).ecause the date of the initial post-implant clinic visit couldary, we cross-referenced the recorded dates of complica-ions from subsequent clinic visits and counted those eventsccurring temporally within 45 days following implantation.hese complications were categorized as major or minor
Table 1), based on the consensus of electrophysiologistsrom all participating hospitals, and was guided by arevious report (10). In general, major complications wereistinguished from minor events by the need for an opera-ion to revise the lead or device or for therapeutic relief.linical complications were considered to be major ifospitalization or substantive parenteral therapy were re-uired. Major complications were subclassified as directimplant-related) or indirect (clinical disease) events. Majoromplications included death unless otherwise specified.atients were deemed to have had “any complication” if theyxperienced a major or a minor complication.actors associated with complications. The variablesonsidered in the univariate analysis were determined aftereview of the literature and included age, sex, prior ventric-lar tachycardia, and primary disease etiology (e.g., isch-mic, nonischemic cardiomyopathy, or other conditionsuch as congenital heart disease or hypertrophic cardiomy-
776 Lee et al. JACC Vol. 55, No. 8, 2010Complications of ICDs February 23, 2010:774–82
ion, revascularization procedure, heart failure, New Yorkeart Association functional class, pre-existing pacemaker
ystem, and atrial fibrillation. Noncardiac factors includedeneral laboratory measures (e.g., serum creatinine concen-ration, estimated glomerular filtration rate, serum sodium,emoglobin) and comorbidities. Medications were also ex-mined, including angiotensin-converting enzyme inhibitor orngiotensin-receptor blocker, beta-adrenoreceptor antagonists,oop diuretic, antiplatelet or anticoagulant drug, amiodarone,nd class IC or other class III antiarrhythmic drugs. Diagnosticnvestigations included QRS interval duration (�140 ms vs.
140 ms), left ventricular ejection fraction (�20%, 21% to5%, or �35%), left ventricular dimension in end-systole ornd-diastole, and left atrial size. We also examined the type ofCD implanted (e.g., dual-chamber, cardiac resynchronizationherapy defibrillator device [CRT-D], or single-chamber de-ice), active versus passive fixation, and single versus dual coilight ventricular lead.tatistical analysis. We performed descriptive analyses ofatients undergoing ICD implant for primary or secondaryrevention indications. We then performed univariate Coxegression analysis to determine predictors of time toomplication after ICD implant. Potential predictors with
� 0.25 on univariate analysis were included in theultiple regression model using a stepwise approach, and
ajor Versus Minor ComplicationsTable 1 Major Versus Minor Complications
Myocardial perforation Lead dislodgement not repositioned
Pericardial tamponade Diaphragmatic stimulation
Pneumothorax/hemothorax Site pain
Pocket infection Lead fracture not requiring intervention
Skin erosion Pocket hematoma
Pocket hematoma requiringintervention
Clinical complications
Pulmonary edema
Electrical storm
Cardiogenic shock
Post implant myocardialinfarction
Hypotension requiringresuscitation
Sepsis
Stroke
Noncerebral embolus
Death
Major nonfatal complications exclude death.
redictors with p � 0.05 in the multivariable model were d
etained. The final model selection was based on clinical andtatistical significance. All models included age irrespectivef statistical significance, because of the potential of thisariable to account for complications.
We determined the association of major complicationsxcluding death (e.g., major nondeath complications) withortality employing complication status as a time-varying
ovariate in Cox regression analysis. In the time-varyingodel, patients were considered complication-free until aajor complication occurred, at which time they were
eclassified. Complications occurring more than 45 daysfter implantation were not included in the determination ofxposure status. We determined the association of majoromplications with death occurring up to 180 days afterefibrillator implant adjusted for age, sex, and ICD type.he preceding analyses were also repeated for minor com-lications. Continuous data are presented as mean � SDnd compared using Student t test. Categorical variablesere compared using the chi-square test, Fisher exact test,r the Mantel-Haenszel test for trend. Exact 95% confi-ence intervals (CIs) were determined using publishedethods. All analyses were performed using SAS software,
ersion 9.1 (SAS Institute, Cary, North Carolina).
esults
atient characteristics. Among a total of 4,217 referrals fore novo ICD from February 2007 to May 15, 2009, patientsere excluded because they refused the procedure (n � 183),nderwent the procedure within 45 days of the last follow-upate (n � 273), or did not meet criteria for the device (n �21). The final study cohort consisted of 3,340 patients, andheir characteristics are shown in Table 2 according to primaryr secondary prevention status. Follow-up data for mortalitynd complications were available for all study patients. Theajority of patients had ischemic heart disease, and nearly
wo-thirds of device implants were for primary preventionndications.
omplication rates. A total of 172 primary (7.4%) and 76econdary (7.6%) prevention patients experienced any com-lication. There was no significant difference in overallomplication rates by primary or secondary preventionndications. Major complications occurred in 90 patients3.8%) undergoing primary prevention ICD and 48 (4.8%)ho underwent secondary prevention device implantation.inor complications occurred in 125 (5.3%) and 45 (4.5%)
f those undergoing primary or secondary prevention defi-rillator implantation. Only a small proportion of compli-ations occurred in-hospital, at rates of 0.5% for major,.5% for minor, and 0.8% for any complication.nivariate predictors of complications. Univariate predic-
ors of major and minor complications are shown in Onlineppendixes 2 and 3, respectively. The most significant factor
ssociated with complications was the type of device im-lanted, with high risk in those undergoing dual-chamber
evice and the highest risk for CRT-D (Fig. 1). The number
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777JACC Vol. 55, No. 8, 2010 Lee et al.February 23, 2010:774–82 Complications of ICDs
f new leads implanted was also a significant predictor of majoromplications, with hazard ratios of 1.78 (95% CI: 1.21 to.63) for 2 leads and 2.17 (95% CI: 1.38 to 3.40) for 3 leads,elative to 1 lead (p � 0.004 and p � 0.001, respectively).
azard ratios (HRs) for minor complications were 1.51 (95%I: 1.06 to 2.15, p � 0.023) and 2.42 (95% CI: 1.64 to 3.56,� 0.001) for 2 and 3 leads, respectively. The risk of major
omplications was also increased in women (HR: 1.57, 95%I: 1.09 to 2.26) and with New York Heart Association
unctional class III to IV (HR: 1.47, 95% CI: 1.04 to 2.08).Minor complications were more likely to occur in women
HR: 1.40, 95% CI: 1.00 to 1.96), those with New Yorkeart Association functional class III to IV (HR: 1.73, 95%I: 1.27 to 2.35), or those with nonischemic dilated
ardiomyopathy (HR: 2.21, 95% CI: 1.35 to 3.61, whenompared with ischemic). Univariate analyses for primaryrevention device were similar to those for de novo im-lants; however, anticoagulant drug use was a significantredictor of complications in the former group. Amonghose taking oral anticoagulants, aspirin or clopidogrel, the
Rs were 2.15 (95% CI: 1.08 to 4.30, p � 0.030) for majornd 1.85 (95% CI: 1.06 to 3.24, p � 0.031) for minoromplications.
ultivariable predictors of complications. Multivariableredictors of complications among de novo ICD recipientsre shown in Table 3. Age was not significantly associatedith major or minor complications and therefore, theseazard ratios are not shown. Dual-chamber and CRT-Defibrillators were the most significant predictors of majoromplications, with �1.5- and 2-fold increase in risk,espectively, compared with those receiving a single-hamber device. Increased left ventricular end-diastolicimension �45 mm was associated with a 1.5-fold increase
n risk. Women were more likely to develop major compli-ations than men (Table 3). Minor complications were alsoncreased in those receiving dual-chamber and CRT-Devices, and in those with nonischemic cardiac diseasetiologies (Table 3).
In the subset of patients undergoing primary preventionCD implantation, device type had an even greater effect onajor complications with a 2.6- and 3.2-fold risk for
ual-chamber and CRT-D, respectively (Table 4). Prior usef antiplatelet agents or anticoagulants increased the risk ofajor complications, as did the use of class IC or class III
ntiarrhythmic drugs other than amiodarone (Table 4).ypes of complications. The complications occurring withighest frequency are shown in Table 5. In some cases,ultiple complications occurred in the same patient. The most
requent major complications were lead-related, followed byocket infection, electrical storm, and pulmonary edema re-uiring hospitalization. The majority of lead replacements (76f 94 � 81%) and lead extractions (21 of 23 � 91%) were notreceded by a lead recall. Incisional infections and pocketematomas that did not require an operative procedure (med-
cally managed) were the most common minor complications. s
ssociation of complications with death. Patients whoxperienced a major complication (excluding death) had aignificantly higher rate of subsequent mortality than thoseithout a major complication within the first 45 days after
CD implantation. Crude mortality rates were 2.2% versus.5% at 45 days (p � 0.036), 2.9% versus 1.2% at 90 days (p �.09), and 5.1% versus 1.8% at 180 days (p � 0.018) for thoseith versus those without a major nonfatal complication within
he first 45 days. Adjusted mortality was significantly increasedn those who experienced a major complication within 45 days,ut not in those with minor complications (Table 6).
In further analyses, we found that mortality rates wereigher among those who experienced any major complica-ion within the 45-day perioperative period compared withhose without complications (Fig. 2). The HR for directmplant-related complications adjusted for age, sex, andCD type was 24.89 (95% CI: 2.11 to 294.26) in the first 45ays following defibrillator implantation (p � 0.01). Pa-ients with indirect clinical complications (excluding death)ccurring within 45 days of ICD implant were associatedith substantially higher mortality rates when comparedith those patients without early complications (Fig. 2).he adjusted HR for indirect clinical complications was2.35 (95% CI: 4.74 to 32.18) in the 180-day follow-uperiod after defibrillator implantation (p � 0.001).
iscussion
n this population-based registry, we found that periopera-ive complications were not infrequent, with 4.1% experi-ncing major complications after de novo defibrillator im-lantation. The predominant factor associated with bothajor and minor complications was the type of device
mplanted, with increased risk in those receiving dual-hamber devices and the highest risk after cardiac resyn-hronization defibrillator implantation. Women and thoseith an enlarged left ventricular chamber size were at
ncreased risk of complications after de novo defibrillatormplantation. Use of anticoagulants or antiplatelet agentsnd antiarrhythmic drugs also predicted increased risk ofomplications among those undergoing a primary preven-ion defibrillator. The occurrence of a major, early compli-ation was associated with an increased risk of death with a- to 4-fold risk up to 6 months after device implantation.tratified by the type of major complication, we found thatoth direct implant-related and indirect clinical complica-ions were associated with significantly increased risk ofeath.Previous studies have reported on selected complications
fter defibrillator implantation. A German ICD registryeported rates of specific complications and found thatocket hematoma, chronic pain, and lead and device dis-
odgements leading to operative revisions were the mostommon events (11). However, participation in this registryas voluntary with considerable losses to follow-up (11). A
ingle-center study spanning a decade of defibrillator im-
778 Lee et al. JACC Vol. 55, No. 8, 2010Complications of ICDs February 23, 2010:774–82
LVEF by RNA or echocardiography 27.0 � 9.5 37.2 � 14.0 �0.001
LVEDD, mm 62.0 � 11.2 56.8 � 9.7 �0.001
LVESD, mm 51.0 � 12.6 43.7 � 11.6 �0.001
Left atrial size, mm 46.0 � 9.9 42.8 � 8.7 �0.001
Type of device implanted
Single-chamber 1,017 (43.4) 453 (45.3) �0.001
Dual-chamber 624 (26.7) 461 (46.1)
CRT-ICD 700 (29.9) 85 (8.5)
RV lead characteristics*
Passive fixation 140 (6.0) 50 (5.0) 0.29
Active fixation 2,198 (93.9) 938 (93.9)
Continued on next page
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779JACC Vol. 55, No. 8, 2010 Lee et al.February 23, 2010:774–82 Complications of ICDs
lantations reported that 10% of patients experienced aomplication within 30 days and that biventricular andual-chamber devices were associated with more lead-elated complications (12). However, this study was small440 patients) and was limited in the ability to definendependent predictors of major complications (12). Aarger multicenter study reported that lead- and pocket-elated complications occurred in 2.1% and 1.8% of cases,espectively, but predictors of these events were not deter-ined (13). The National Cardiovascular Data Registry
CD Registry reported in-hospital complication rates of.3% for major and 3.6% for any complication (14); thategistry differed from our study because reporting was notandatory from all hospitals (15,16), in-hospital complica-
ions were the primary events counted, and lead complica-ions were not included (14).
Previous studies evaluating defibrillator complicationssing large administrative databases have reported differentvent rates and predictors. Using Medicare administrativeatabases, 90-day complications were reported to haveccurred in 14.2% of patients (17). Many of the majoromplications in this study overlapped with ours; however,
0%
5%
10%
SingleChamber
DualChamber
CRT-D
0%
5%
10%
SingleChamber
DualChamber
CRT-D
Major complications by ICD type (p-trend <0.001)
Minor complications by ICD type(p-trend <0.001)
% M
ajo
rC
om
plic
atio
n%
Min
or
Co
mp
licat
ion
Single Dual CRT-DChamber Chamber
Single Dual CRT-DChamber Chamber
Figure 1 Rates of 45-Day Complications by Defibrillator Type
Rates of major (top) and minor (bottom) 45-day complications by defibrillatortype. CRT-D � cardiac resynchronization therapy defibrillator; ICD � implant-able cardioverter-defibrillator.
ContinuedTable 2 Continued
Characteristic Primary Prev
Number of RV coils†
Single coil 100 (4.3
Dual coil 2,237 (95
Values are n (%) or mean � SD. *Right ventricular lead data availablecoil data available for 2,337 primary and 985 secondary prevention p
radionuclide angiogram; TIA � transient ischemic attack.
t
he predictors differed and were predominantly noncardiacomorbidities (17). Our study differed because we consid-red an early post-procedural time window, which reflectsomplications related to device implantation, and further-ore, we used clinically obtained data on predictors and
vents. Importantly, another study of Medicare beneficiariesound that in-hospital complications occurred in 10.8% ofCD recipients and led to significant increases in length ofospital stay and costs compared with an uncomplicatedrocedure (18).Our study is novel because the data were collected in a
rospective, population-based registry, with detailed longi-udinal follow-up. We also examined outcomes bimodally,sing a combination of both clinical device and passivedministrative data-based follow-up, allowing for capturef important outcomes including death. Our study addso the current literature in several ways. First, we exam-ned complications that occurred in the early post-efibrillator implant period including events followingischarge (19). Second, this registry was mandated by thedministrator of health care services in Ontario, andarticipation from all defibrillator implanting centers wasequired. Thus, our study was not subject to volunteerias, and we were able to study all patients irrespective ofge. Finally, a wide array of potential clinical predictorsnd major and minor complications, including death,ere systematically evaluated.The potential mechanisms of the mortality association
ith major complications may be a direct or indirect resultf complications. The early mortality effects of majoromplications may be the direct consequence of a mechan-cal procedure-related event (e.g., myocardial perforation).hese mechanical complications were potentially related to
ncreasing procedural complexity with greater number ofeads implanted, and anticoagulation or antiplatelet agentsn the subgroup of patients undergoing primary preventionefibrillators. The latter is particularly relevant given theendency of some to implant defibrillators without discon-inuation of oral anticoagulants combined with bridgeherapy (20,21). The mortality effects of indirect clinicalomplications began early and were maintained up to 180ays following implantation, likely reflecting progressiveisease of the underlying cardiovascular disease substrate
Secondary Prevention p Value
27 (2.7) 0.035
958 (95.9)
8 primary and 988 secondary prevention patients. †Right ventricular.
hat predisposed to a higher a priori risk of death. The
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780 Lee et al. JACC Vol. 55, No. 8, 2010Complications of ICDs February 23, 2010:774–82
ssociation of enlarged left ventricular chamber size withomplications may reflect altered biventricular and atrialeometry, which confer both an increased propensity tooth mechanical complications and increased clinicalisk. We have previously shown that heart failure eventsontribute significantly to reduced survival (22), androgressive heart failure substantially increases the risk ofeath among defibrillator recipients who have experi-nced an appropriate therapy (23), signifying the impor-ance of this condition on outcomes after device implan-ation. High mortality rates have been reported in thoseith electrical storm (24,25), but the data are conflicting
26), and prior studies have not examined this in the
Multivariable Predictors of Complications in All(e.g., Primary and Secondary Prevention)Table 3 Multivariable Predictors of Complic(e.g., Primary and Secondary Preve
Major complications*
Women
Secondary vs. primary prevention
Nonischemic vs. ischemic CM
Other cardiac disease vs. ischemic CM
Anticoagulation, aspirin or clopidogrel vs. none
Amiodarone vs. none
Class 1 or other class 3 AAD vs. none
LVESD �45 mm vs. �45 mm
Dual vs. single-chamber ICD
CRT-D vs. single-chamber
Minor complications*
Women
Secondary vs. primary prevention
Nonischemic vs. ischemic CM
Other cardiac disease vs. ischemic CM
Anticoagulation, aspirin, or clopidogrel vs. none
Dual- vs. single-chamber ICD
CRT-D vs. single-chamber
*Age not significant in multivariable model; hazard ratio for age not sCI � confidence interval; CM � cardiomyopathy; CRT-D � cardiac resy
other abbreviations as in Table 2.
Multivariable Predictors of Complications in PrimTable 4 Multivariable Predictors of Complic
Major complications*
Women
Anticoagulation, aspirin or clopidogrel vs. none
Amiodarone vs. none
Class 1 or other class 3 AAD vs. none
Dual-chamber vs. single-chamber ICD
CRT-D vs. single-chamber
Minor complications*
Women
Nonischemic vs. ischemic CM
Other cardiac disease vs. ischemic CM
Dual- vs. single-chamber ICD
CRT-D vs. single-chamber
*Age not significant in multivariable model; hazard ratio for age not shown.Abbreviations as in Tables 2 and 3.
ontext of complications arising in the perioperativehase. The use of antiarrhythmic drugs reflects underly-ng abnormalities in the electrical substrate, which mayave conferred an increase in clinical complicationsecause of more severe structural disease.Few studies have systematically examined the predictors
f major and minor complications according to indicationor the ICD using multivariable analysis. Our study suggestshat early complications of ICD implantation are notnfrequent and suggest an increased risk of death if majoromplications occurred. These data also suggest that com-lications are driven in part by the underlying sickness of theatient, and these factors may be attenuated by optimization
781JACC Vol. 55, No. 8, 2010 Lee et al.February 23, 2010:774–82 Complications of ICDs
f the underlying cardiac disease before defibrillator implan-ation. This may be most relevant for patients who areeferred for CRT-D, who are those at greatest risk ofomplications driven by heart failure and their underlyingardiac status. Although near-term death was infrequent inefibrillator recipients, the association should also be exam-
ned in other cohorts because of the importance of thisutcome. Minor complications remain clinically importantecause these events may influence quality of life, buturther data are needed to determine the degree of thisssociation. Finally, it should carefully be consideredhether patients require more complex, multilead devices aspposed to simpler devices with fewer leads.tudy limitations. Although we identified a number ofredictors of complications, we could not determine theausal pathway by which these factors exerted their effects.t is possible that these effects may be complex, exertingheir effects on subcomplications by a multitude of mecha-isms. We did not examine intraoperative factors such asrocedure duration; however, it would likely have been
onger with implantation of more complex devices. We did
Frequent Major and Minor ComplicationsTable 5 Frequent Major and Minor Complica
NumbOccurr
Major complications*
Lead replacement 94
Lead repositioning 67
Pocket infection requiring debridement 40
Electrical storm 33
Lead dislodgement with repositioning 29
Lead extraction 23
Pulmonary edema 24
Myocardial perforation 15
Pneumothorax/hemothorax 13
Post-implant myocardial infarction 8
Sepsis 8
Cardiogenic shock 7
Minor complications*
Incisional infection 38
Pocket hematoma 41
Lead dislodgement not repositioned† 28
Subclavian vein thrombosis 8
*Only complications with frequency �5 are shown. †Lead dislodgeme
djusted Hazard Ratios for Mortality According toresence of a Major Nondeath Complicationithin 45 DaysTable 6
Adjusted Hazard Ratios for Mortality According toPresence of a Major Nondeath ComplicationWithin 45 Days
HazardRatio 95% CI p Value
Any major complication excluding death
Adjusted for age and sex 3.79 1.69–8.51 0.001
Adjusted for age, sex, and ICD type 3.70 1.64–8.33 0.002
Minor complication
Adjusted for age and sex 1.12 0.35–3.62 0.85
Adjusted for age, sex, and ICD type 1.08 0.33–3.50 0.90
bbreviations as in Table 3.
ot examine those undergoing replacement devices, forhom the predictors and consequences of complicationsay differ substantially from these findings. Lastly, our data
uggested an association of major complications with mor-ality, but could not determine whether the complicationas causally related to death.
onclusions
significant proportion of patients undergoing de novomplantation of cardioverter defibrillators experienced com-lications. The complexity of device implanted, female sex,nd enlarged left ventricular dimension were significant
0%
5%
10%
15%
20%
25%
30%
35%
45 d 90 d 180 d
No ComplAnyClinical
30%
35%
40%
20%
15%
10%
5%
0%*
*
†
†
‡
p <0.05‡ p <0.01† p <0.001
*
Mo
rtal
ity
Rat
e
Figure 2 Mortality Rates for DefibrillatorRecipients With or Without Complications
Mortality rates at 45, 90, and 180 days for defibrillator recipients with clinicalcomplications, any complication (implant-related or clinical), and no complica-tions. The p values for comparison with no complication group are shown.Any � any complication (major or minor); compl � complication.
Number ofPatients Affected
% PatientsWith Complication
90 2.7
67 2.0
32 1.0
29 0.9
28 0.8
23 0.7
21 0.6
14 0.4
13 0.4
8 0.2
7 0.2
6 0.2
35 1.1
33 1.0
27 0.8
8 0.2
out replacement or repositioning.
tions
er ofences
prpots
RIBd
R
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
Kr
FD
782 Lee et al. JACC Vol. 55, No. 8, 2010Complications of ICDs February 23, 2010:774–82
redictors of major complications. Because direct implant-elated complications and indirect disease-related majorerioperative events were associated with an increased riskf death, further evaluations of early defibrillator complica-ions, their potential effects on mortality, and preventativetrategies are needed.
eprint requests and correspondence: Dr. Douglas S. Lee,nstitute for Clinical Evaluative Sciences, Room G-106, 2075ayview Avenue, Toronto, Ontario M4N 3M5, Canada. E-mail:[email protected].
EFERENCES
1. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantablecardioverter-defibrillator for congestive heart failure. N Engl J Med2005;352:225–37.
2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of adefibrillator in patients with myocardial infarction and reduced ejec-tion fraction. N Engl J Med 2002;346:877–83.
3. The Antiarrhythmics Versus Implantable Defibrillators (AVID) In-vestigators. A comparison of antiarrhythmic-drug therapy with im-plantable defibrillators in patients resuscitated from near-fatal ventric-ular arrhythmias. N Engl J Med 1997;337:1576–83.
4. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantabledefibrillator study (CIDS): a randomized trial of the implantablecardioverter defibrillator against amiodarone. Circulation 2000;101:1297–302.
5. Lee DS, Tu JV, Austin PC, et al. Effect of cardiac and noncardiacconditions on survival after defibrillator implantation. J Am CollCardiol 2007;49:2408–15.
6. Al-Khatib SM, Anstrom KJ, Eisenstein EL, et al. Clinical andeconomic implications of the Multicenter Automatic DefibrillatorImplantation Trial-II. Ann Intern Med 2005;142:593–600.
7. Lee DS, Birnie D, Cameron D, et al. Design and implementation ofa population-based registry of Implantable Cardioverter Defibrillators(ICDs) in Ontario. Heart Rhythm 2008;5:1250–6.
8. Tu JV, Willison DJ, Silver FL, et al. Impracticability of informedconsent in the Registry of the Canadian Stroke Network. N EnglJ Med 2004;350:1414–21.
9. Kron J, Herre J, Renfroe EG, et al. Lead- and device-relatedcomplications in the antiarrhythmics versus implantable defibrillatorstrial. Am Heart J 2001;141:92–8.
0. Gould PA, Krahn AD. Complications associated with implantablecardioverter-defibrillator replacement in response to device advisories.JAMA 2006;295:1907–11.
1. Gradaus R, Block M, Brachmann J, et al. Mortality, morbidity, andcomplications in 3344 patients with implantable cardioverter defibril-lators: results from the German ICD Registry EURID. Pacing ClinElectrophysiol 2003;26:1511–8.
2. Alter P, Waldhans S, Plachta E, Moosdorf R, Grimm W. Compli-cations of implantable cardioverter defibrillator therapy in 440 consec-utive patients. Pacing Clin Electrophysiol 2005;28:926–32.
3. Gold MR, Peters RW, Johnson JW, Shorofsky SR, the World-Wide
Jewel Investigators. Complications associated with pectoral implanta- p
tion of cardioverter defibrillators. Pacing Clin Electrophysiol 1997;20:208–11.
4. Peterson PN, Daugherty SL, Wang Y, et al. Gender differences inprocedure-related adverse events in patients receiving implantablecardioverter-defibrillator therapy. Circulation 2009;119:1078–84.
5. Anderson KP. Estimates of implantable cardioverter-defibrillatorcomplications: caveat emptor. Circulation 2009;119:1069–71.
6. Gibbs JL, Monro JL, Cunningham D, Rickards A. Survival aftersurgery or therapeutic catheterisation for congenital heart disease inchildren in the United Kingdom: analysis of the central cardiac auditdatabase for 2000-1. BMJ 2004;328:611.
7. Al-Khatib SM, Greiner MA, Peterson ED, Hernandez AF, SchulmanKA, Curtis LH. Patient and implanting physician factors associatedwith mortality and complications following implantable cardioverter-defibrillator implantation, 2002–2005. Circ Arrhythm Electrophysiol2008;1:240–9.
8. Reynolds MR, Cohen DJ, Kugelmass AD, et al. The frequency andincremental cost of major complications among Medicare beneficiariesreceiving implantable cardioverter-defibrillators. J Am Coll Cardiol2006;47:2493–7.
9. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. Theincidence and severity of adverse events affecting patients after dis-charge from the hospital. Ann Intern Med 2003;138:161–7.
0. Tischenko A, Gula LJ, Yee R, Klein GJ, Skanes AC, Krahn AD.Implantation of cardiac rhythm devices without interruption of oralanticoagulation compared with perioperative bridging with low-molecular weight heparin. Am Heart J 2009;158:252–6.
1. Tolosana JM, Berne P, Mont L, et al. Preparation for pacemaker orimplantable cardiac defibrillator implants in patients with high risk ofthrombo-embolic events: oral anticoagulation or bridging with intra-venous heparin? A prospective randomized trial. Eur Heart J 2009;30:1880–4.
2. Lee DS, Austin PC, Stukel TA, et al. “Dose-dependent” impact ofrecurrent cardiac events on mortality in patients with heart failure.Am J Med 2009;122:162–9.
3. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance ofdefibrillator shocks in patients with heart failure. N Engl J Med2008;359:1009–17.
4. Sesselberg HW, Moss AJ, McNitt S, et al., on behalf of theMADIT-II Research Group. Ventricular arrhythmia storms in postin-farction patients with implantable defibrillators for primary preventionindications: a MADIT-II substudy. Heart Rhythm 2007;4:1395–402.
5. Exner DV, Pinski SL, Wyse DG, et al., on behalf of the AVIDInvestigators. Electrical storm presages nonsudden death: the antiar-rhythmics versus implantable defibrillators (AVID) trial. Circulation2001;103:2066–71.
6. Brigadeau F, Kouakam C, Klug D, et al. Clinical predictors andprognostic significance of electrical storm in patients with implantablecardioverter defibrillators. Eur Heart J 2006;27:700–7.
ey Words: implantable defibrillators y complications y outcomesesearch y mortality y quality of care.
APPENDIX
or a list of participating hospitals and investigators in the Ontario ICDatabase and the univariate predictors of major and minor complications,
