Dr Yue Chiu Sun Consultant and Head Division of Cardiology

Dept of Medicine & GeriatricsUnited Christian Hospital

6 Apr 2014

Case 1Mr. WWK age 51Non-smoker, non-drinkerPMH:

psoriasis Mother diagnosed to have HOCMfamily screening previously

recommended

Presentation Played badminton after work -> sudden

collapseBystander CPR started Ambulance crew arrived

VF

At AED BP 133/92 P 120 bpm

Given amiodarone infusionGCS 3/15

PERLIntubated for ventilatory support

Consulted CCU-> admitted for further management

ECG abnormality?

At CCUBedside Echo

Fair echogenicityOverall satisfactory LV systolic function No apparent RWMA notedNo LVH noted to suggest HCM or LVOT

obstructionNo pericardial effusion

Seizuregiven sodium valproate 400 mg q8h ivUrgent CT brain: no SOL / haemorrhage

ProgressConsulted ICUAdmitted ICU

Therapeutic hypothermia sedation (dormicum, morphine) + muscle relaxant

(atracurium) induction with 2.5L of 4°C ice cold saline aimed at body T 32-34°C; maintained with wet

blankets continued rectal probe monitoring

Inotropic supportNG tube feeding startedECG : ST↑V2-3 and T V2-4 LDH 301 → 288; CK 395 → 932TnT 33 → 1169aspirin 160 mg daily PO started

During Hypothermia

ProgressECG : deep T over V2-6 (probable ACS :

Anterior NSTEMI)Echo:

- LV anteroseptal & apical hypokinesia; impaired LV function

Re-warming with 0.25 °C per hrReduced inotropic support graduallyExtubated the next day -> transferred

back to CCU

To CCUClopidogrel, Simvastatin, Metoprolol were

addedbedside echo: LVEF 50%, fair LV contraction;

RWMA noted (similar to ICU findings)Fully alert, not in heart failure

Coronary angiogram and PCI was performedR dominance, LM normal, LAD proximal 80%,

mid LAD 70% stenosis, LCx mild disease, RCA normal

Stenting to proximal and mid LAD

Uneventful recovery and discharged home

Post-PCI

Anterior STEMI: Therapeutic Hypothermia and Primary PCI

Post-Cardiac Arrest Care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Recommend that comatose (ie, lack of meaningful response to verbal commands) adult patients with ROSC after out-of-hospital VF cardiac arrest should be cooled to 32°C to 34°C (89.6°F to 93.2°F) for 12 to 24 hours (Class I, LOE B)

Induced hypothermia also may be considered for comatose adult patients with ROSC after in-hospital cardiac arrest of any initial rhythm or after out-of-hospital cardiac arrest with an initial rhythm of pulseless electric activity or asystole (Class IIb, LOE B)

Circulation. 2010;122:S768-S786

Post–cardiac arrest care algorithm

Peberdy M A et al. Circulation. 2010;122:S768-S786

Copyright © American Heart Association, Inc. All rights reserved.

Case 2Mr WWM age 52History of idiopathic DCMP (CTCA-> normal coronary arteries) and AF

Admitted for post-VT/VF arrest after being found collapse in street (pulseless VT/VF with prolonged resuscitation > 1 hr and repeated defibrillation); intubated for mechanical ventilation

VT after admission

ProgressAcute renal and liver failure requiring

temporary HD supportProgressive improvement and extubated laterEcho: poor LV function EF ~20% with global

hypokinesiaCoronary angiogram: mild CAD onlyICD was implanted Transfer to convalescence hospital for

rehabilitation, good neurological recovery

Diagnostic Approach to SCD survivor

1. Clinical Historyeg. known IHD/congenital heart disease or past

history of MI, CV risk profile, triggering factors (exercise, stress – eg. ACS, WPW, HCM, AS, CPVT )

2. Family history of hereditary cardiac arrhythmia or congenital heart disease, FH of SCD

3. Transient and reversible causes 4. Evaluation for structural heart disease 5. Evaluation for those without structural heart

disease

Clinical History and Baseline Investigation

Transient or reversible causes Evidence of ACS esp. STEMI Drug history: anti-arrhythmic drugs,

psychiatric drugs, OTC drugs, herbal medicine, drug abuse

Medications esp. those ↑ QTcElectrolyte and acid-base abnormalities:

hypokalemia K, hyperkalemia ↑K, Ca, acidosis

Investigations for SCD survivor1. ECG

- Myocardial ischemia or infarction (? ST elevation in V1 & aVR)

- myocarditis (eg. T wave inversion, ST segment elevation or depression, heart block, ↑QT interval)

- high grade AV block- Brugada Syndrome (polymorphic VT/VF)- Long QT or short QT- Wolf-Parkinson-White WPW syndrome esp. preexcited AF - CPVT, Early repolarization syndrome (ERS)

ECGPR: short PR (WPW with preexcitation)Q wave: MIQRS: delta wave, BBBQT : congenital long QT, acquired QT : short QTST : STEMI, myocarditis, Brugada syndromeST : myocardial ischemia, NSTEMI, myocarditisT : tall T wave in K, hyperacute phase in AMIT : myocardial ischemia, NSTEMI, epsilon wave

(ARVC)P and QRS relationship: high grade AV blockJ point elevation

ECG diagnosis?

Brugada ECG

Brugada ECG

Brugada syndrome: polymorphic VT/VF

WPW with preexcited AF

Early repolarization syndrome ERS ERS is defined as an elevation of the J point (the junction between the end of the QRS complexand the beginning of the ST segment) and/or ST segment by at least 0.1 mV from baseline

Early repolarization syndrome ERS

ERS can be divided into three subtypes:Type 1 - which is predominantly characterized by an ERP that is detected with lateral precordial leads, is prevalent among healthy male athletes and rarely seen in VF survivors

Type 2 - which is predominantly detected through the inferior or inferolateral leads, is associated with a higher level of arrhythmia risk than type 1 ERS

Type 3 - which involves ERPs that are observed globally through the inferior, lateral, and right precordial leads, is associated with the highest level of risk for malignant arrhythmias and often associated with VF storms

Early repolarization syndrome ERS

early repolarization in the inferior ECG leads has been associated with idiopathic VF and has been termed as ERS

ERS has emerged as a marker of risk for idiopathic VF and sudden death. However, the incidental discovery of a J wave on routine screening should not be interpreted as a marker of “high risk” for sudden death

Ann Noninvasive Electrocardiol 2014;19(1):15–22

Catecholaminergic Polymorphic VT (CPVT)

Affected patients typically present with life-threatening VT or VF occurring during emotional or physical stress, with syncope often being the first manifestation of the disease. Although sporadic cases occur, this is a largely familial disease . The majority of known cases are due to mutations in the cardiac ryanodine receptor, which is the cardiac sarcoplasmic calcium release channel

VT morphology may vary continuously, from beat to beat, or may appear as a bidirectional VT

Congenital Long QT syndrome LQTS With 4 or more points the probability is high for LQTS, and with 1 point or less the

probability is low. Two or 3 points indicates intermediate probability.

QTc (Defined as QT interval / square root of RR interval)

o >= 480 msec - 3 points

o 460-470 msec - 2 points

o 450 msec and male gender - 1 point

Torsades de Pointes ventricular tachycardia - 2 points

T wave alternans - 1 point

Notched T wave in at least 3 leads - 1 point

Low heart rate for age (children) - 0.5 points

Syncope (one cannot receive points both for syncope and Torsades de pointes)

o With stress - 2 points

o Without stress - 1 point

Congenital deafness - 0.5 points

Family history (the same family member cannot be counted for LQTS and sudden

death)

o Other family members with definite LQTS - 1 point

o Sudden death in immediate family (members before the age 30) - 0.5

points

Long QT1

Congenital Long QT syndromeGene Syndrome Frequency Locus

Protein (Functional

Effect)

KCNQ1 (LQT1) RWS, JLNS 40–55 11p15.5 Kv7.1 (↓)

KCNH2 (LQT2) RWS 30–45 7q35–36 Kv11.1 (↓)

SCN5A (LQT3) RWS 5–10 3p21–p24 NaV1.5 (↑)

ANKB (LQT4) RWS <1% 4q25–q27 Ankyrin B (↓)

KCNE1 (LQT5) RWS, JLNS <1% 21q22.1 MinK (↓)

KCNE2 (LQT6) RWS <1% 21q22.1 MiRP1 (↓)

KCNJ2 (LQT7) AS <1% 17q23 Kir2.1 (↓)

CACNA1C (LQT8)

TS <1% 12p13.3L-type calcium

channel (↑)

CAV3 (LQT9) RWS <1% 3p25 Caveolin 3 (↓)

SCN4B (LQT10) RWS <1% 11q23.3Sodium channel-

β4 (↓)

AKAP9 (LQT11) RWS <1% 7q21–q22 Yotiao (↓)

SNTA1 (LQT12) RWS <1% 20q11.2Syntrophin α1

(↓)

KCNJ5 (LQT13) RWS <1% 11q24 Kir3.4 (↓)

Short QT syndrome

Genetic basis of SQTS

  QTc (msec) LocusGene (cardiac ion channel)

SQT 1 286 ± 6 11p15 KCNH2 (IKr) ↑

SQT 2 302 7q35 KCNQ1 (IKs) ↑

SQT 3 315-330 17q23 KCNJ2 (IK1) ↑

SQT 4 331-370 10p12CACNB2b (ICa) ↓

SQT 5 346-360 12p13CACNA1C (ICa) ↓

SQT 6 330 7q21-22CACNA2D1 (ICa) ↓

Investigations for SCD survivor2. Blood tests

eg. RFT, ABG, cardiac biomarkers, Ca, Mg, drug level (digoxin, TCA etc.), toxicology screen

Investigations for SCD survivor

3. Echocardiogram- LV function and EF, RWMA, heart

chamber size- significant valvular disease eg. aortic

stenosis- cardiomyopathy eg. DCM, HCM/HOCM,

ARVC

Investigations for SCD survivor4. Coronary angiography and cardiac catheterization

- r/o significant coronary artery disease, anomalous coronary arteries (? coronary artery course between aorta & pulmonary trunk), congenital heart disease5. CT scan

- aortic dissestion, coronary anomaly, congenital heart disease6. Cardiac MRI

- structural heart disease eg. HCM, ARVC, LV non-compaction

Investigations for SCD survivor7. EP study (limited role : post-cardiac arrest)

- exclude other arrhythmias, ablative therapy (?WPW, VT foci)

8. Genetic testing, family screening and counselling

eg. long QT, HCM, Brugada syndrome, CPVT- commercially available genetic testing

exists for HCM, DCM, ARVC, LV non-compaction, LQTS, SQTS, CPVT, and BrS

Genetic Testing for Potentially Lethal, Highly Treatable Inherited Cardiomyopathies/Channelopathies in Clinical Practice

David J. Tester and Michael J. Ackerman

Circulation. 2011;123:1021-1037

Indications for genetic testing. Provided is a table of possible indications for genetic testing for hypertrophic cardiomyopathy (HCM), long-QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS). LVH indicates left ventricular hypertrophy; QTc, corrected QT interval; TdP, torsade de pointes; Neg., negative; and SUD, sudden unexplained death. The plus symbol ( ) represents a positive indication for genetic testing; the negative symbol ( ) represents an indicator that does not warrant genetic testing for the specific disorder; and the / symbol represents an indicator that may or may not warrant genetic testing.

Utility of genetic testing. Shown is the current diagnostic, prognostic, and therapeutic utility of genetic testing for hypertrophic cardiomyopathy (HCM), long-QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS). The plus symbol ( ) indicates the test has utility, the negative symbol ( ) indicates no current measurable utility, and the / symbol indicates the test may have some utility