Invasive Risk Stratification: When is it needed?

Inherited Cardiomyopathies and Channelopathies: Who is at risk for Sudden Cardiac Death? Invasive Risk Stratification: When is it needed? Hung-Fat Tse, MD, PhD Department of Medicine The University of Hong Kong Queen Mary Hospital Hong Kong

Inherited channelopathies Long QT Syndrome Short QT Syndrome Catecholaminergic polymorphic ventricular tachycardia Brugada Syndrome

Long QT Syndrome 15 pts with LQTS with syncope or cardiac arrest Neither the inducibility of non-sustained VT nor the results of drug testing with beta- blockers proved to be of any prognostic value Spontaneous and Inducible VF in patients with LQTS Conclusion: EPS are of limited value in the diagnosis and treatment of pts with LQTS Bhandari AK, et al. Circulation 1985;71: 63-71

Short QT Syndrome 18 pts with SQTS presented with syncope/scd or Dx during family screening underwent EPS mean vent ERP 155ms (CL 500-600ms) and 150ms (CL 400-430), and inducible VF in 11/18 (61%). In 6 pts with VF and SCD, only 3 pts (50%) had inducible VF on EPS. Conclusion: EPS are of limited value in the diagnosis and treatment of pts with SQTS Giustetto C, et al. Eur Heart J 2006;27: 2440-2447

Inherited channelopathies Long QT Syndrome Short QT Syndrome Catecholaminergic polymorphic ventricular tachycardia Brugada Syndrome

Catecholaminergic polymorphic ventricular tachycardia 19 pts with CPVT underwent EPS Polymorphic non-sustained VT was induced by EPS in 2/19 (11%) pts and 6 pts (31%) with polymorphic non-sustained VTwas induced during isoproterenol infusion 11/19 pts (58%) were not inducible. Conclusions: Low sensitivity and specificity of EPS for symptomatic CPVT pts Priori SG, et al. Circulation 2002;106;2426-34

Inherited channelopathies Long QT Syndrome Short QT Syndrome Catecholaminergic polymorphic ventricular tachycardia Brugada Syndrome

Brugada Syndrome Benito B, et al. Prog Cardiovas Dis 2008;51:1-22

Variation of ECG Pattern in Brugada Syndrome Richter S, et al. Eur Heart J 2010

PHARMACOLOGICAL TESTS Suspicion of Brugada Syndrome and a nondiagnostic ECG Drug challenge tests Drug Dosage and Administration (3) Ajmaline 1 mg/kg over 5 min, IV Flecainide 2 mg/kg over 10 min, IV (400 mg, PO) Procainamide 10 mg/kg over 10 min, IV Plisicainide 1 mg/kg over 10 min, IV Never forget to place V 1 and V 2 in 2 nd And 3 rd intercostal space!!! 1. Hong et al. Circ 2004 2. Meregalli et al JCE 2006 3. Antzelevich et al. Circ 2005 4. Mivamoto et al. Am J Cardiol. 2007

Brugada Syndrome Benito B, et al. Prog Cardiovas Dis 2008;51:1-22

Benito B, et al. Prog Cardiovas Dis 2008;51:1-22

Brugada Series Patients Without Prior Cardiac Arrest Multivariate analysis (Independent predictors of events) HR 95% CI P Inducibility in EPS 5.88 2.0-16.7 0.0001 Syncope 2.51 1.5-5.3 0.017 Basal ECG 2.86 0.7-12.3 0.103 30 25 20 15 10 5 0 Inducible Non inducible ECG+syncope ECG+asymptomatic ECG-syncope ECG - asymptomatic Berruezo AJ. HRS 2010

Brugada Series Probability of SCD During Life-Time 45,1 50 40 30 20 10 0 35,5 23,4 4,4 17 3 Inducible Non inducible 11 7,6 ECG - male ECG - female ECG + male ECG + female Berruezo AJ. HRS 2010

Brugada Series: ICD Pts SYMPTOMS Yes : sudden death 79 patients Events : 37/79 (47%) HIGH RISK Yes : syncope 81 patients Events : 21/81 (26%) HIGH RISK No (asymptomatic) 98 patients Events : 11/98 (11%) INTERMEDICATE RISK BASAL ECG Abnormal 83 patients Events : 11/83 (13%) INTERMEDICATE RISK Normal 15 patients Events : 0/15 (0%) LOW RISK Yes 68 patients Events : 11/68 (16%) INTERMEDICATE RISK INDUCIBILITY ON EPS No 15 patients Events : 0/15 (0%) LOW RISK Berruezo AJ. HRS 2010

Number of Patients with EPS Electrophysiological Study in Brugada Syndrome 500 59% 450 400 350 300 59% 250 Brugada series 200 18% 23% Others 150 18% 23% 100 50 0 Cardiac Arrest Syncope Asymptomatic Paul M, et al. Eur Heart J 2007; 28: 2126-33

Asymptomatic Brugada Syndrome Paul M, et al. Eur Heart J 2007; 28: 2126-33

% of Patients Asymptomatic Brugada Syndrome 2% VF 80 70 60 50 1% VF 40 30 20 12% VF 4% VF Others 10 0 EPS -ve EPS +ve Brugada series Paul M, et al. Eur Heart J 2007; 28: 2126-33

Asymptomatic Brugada Syndrome Japanese Probands N=330, mean age 50 232 pts underwent EPS 57% of asymptomatic pt (n=154, 63%) with inducible VF Mean FU 4 yrs European Probands N=1029, mean age 45 638 pts underwent EPS 37% of asymptomatic pt (n=654, 64%) with inducible VF Mean FU 3 yrs Kamakura S, et al. Circ Arrhythm EP 2009 Probst et al. Circulation 2009

Asymptomatic Brugada Syndrome 100 Japanese Study Europe (FINGER) Study Arrhythmia free survival Asymptomatic Arrhythmia free survival Asymptomatic 100 Syncope Syncope 80% Cardiac arrest 80% Cardiac arrest 60% 60% 100 10 30 50 70 Months follow-up Drug-induced Type I 12 36 56 72 Months follow-up 100 Drug-induced Type I 80% Spontaneous Type I 80% Spontaneous Type I p=0.16 10 30 50 Months follow-up 70 Kamakura S, et al. Circ Arrhythm EP 2009 p=0.01 12 36 56 72 Months follow-up Probst et al. Circulation 2009

Asymptomatic Brugada Syndrome Data on outcome of asymptomatic patients with type I Brugada ECG with INDCIBLE VF Japanese Study Spontaneous Type I 57 Inducible VF Drug-induced type I 34 32 (56%) 20 (58%) Spontaneous VF at 4 years 1/32 = 3% 0/20 = 0 1/52 = 2% Europe FINGER Study Spontaneous Type I 172 Inducible VF Drug-induced type I 197 63 (37%) 74 (37%) Spontaneous VF at 5 years 1/63 = 2% 3/74 = 4% 4/137 = 3% Kamakura S, et al. Circ Arrhythm EP 2009 Probst et al. Circulation 2009

Asymptomatic Brugada Syndrome Japanese Study Arrhythmia free survival Europe (FINGER) Study Arrhythmia free survival 100 Negative EPS 100 Negative EPS 80% Inducible VF 80% Inducible VF p=0.16 p=0.05 60% 60% 40% 10 30 50 70 Follow-up (months) 40% 24 48 72 Follow-up (months)

Data on outcome of asymptomatic patients with type I Brugada ECG with INDUCIBLE VF Data on the Japanese Study and the European FINGER study combined This risk for arrhythmic events -- at 4-5 years -- for asymptomatic patients with inducible VT is : 1/52 + 4/137 = 5/189 = 2.6% Upper limit of the 95% confidence interval = 6% Japanese Study Europe FINGER Study Brugada Series 6% 1/52 + 4/137 + 11/68 = 16/257 Viskin S. HRS 2010

Data on outcome of asymptomatic patients with type I Brugada ECG with NEGATIVE EPS Data on the Japanese Study and the European FINGER study combined This risk for arrhythmic events -- at 4-5 years -- for asymptomatic patients who are NOT inducible 2/39 + 2/76 = 4/115 = 3.5% Upper limit of the 95% confidence interval = 8% And for asymptomatic patients with spontaneous Type I who are NOT inducible : 2/25 + 2/109 = 4/134 = 3% Upper limit of the 95% confidence interval = 7% Viskin S. HRS 2010

Current ACC/AHA/ESC Guideline Long QTS/ CPVT No recommendation for EP testing Brugada Syndrome Class IIb. EP testing may be considered for risk assessment for SCD in pts with ARVC/D (level of evidence C)

Inherited Cardiomyopathy Hypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular Cardiomyopathy Maron BJ. Cardiovas Path 2010 Buja G, et al. Prog Cardiovas Dis 2008

Hypertrophic Cardiomyopathy Asymptomatic Symptomatic Pts with inducible VT on EPS had higher event rate But, predictive accuracy is very low Fananapazir L, et al. Circulation 1992

Arrhythmogenic Right Ventricular Cardiomyopathy The prognostic role of EPS in patients with ARVC/D is controversial. Majority of data are based on retrospective analysis of ARVD pts who underwent ICD implant low predictive accuracy of EPS in pts with definite ARVC/D Pts with probable ARVC/D and ve EP study may represent a low risk group Roguin A, et al. JACC 2004 Piccini JP, et al. Heart Rhythm 2005

Current ACC/AHA/ESC Guideline Hypertrophic Cardiomyopathy Class IIb. EP testing may be considered for risk assessment for SCD in pts with HCM (level of evidence C) Arrhythmogenic Right Ventricular Cardiomyopathy Class IIb. EP testing may be considered for risk assessment for SCD in pts with ARVC/D (level of evidence C)

Conclusions Risk stratification for SCD with EP study in subjects with inherited channelopathy and cardiomyopathy remain challenging No role for invasive EP study in symptomatic pts with LQTS/SQTS/CPVT, but role in asymptomatic subjects unclear? Controversy over the role of EP study in asymptomatic Brugada syndrome/hocm and ARVD role in uncertain case?