Tailored treatment in Brugada syndrome

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1 Tailored treatment in Brugada syndrome Lars Eckardt Department of Cardiology and Angiology Division of Experimental and Clinical Electrophysiology University of Münster, Germany

2 45 yr old male preoperative routine ECG asymptomatic FHx: 1 brother (SCD aged 45) 2 healthy brothers father died aged 85 (cancer) mother (79 years)

3 What would you do? Nothing Quinidine ICD depending on EP study ICD

4 Brugada Syndrome I avr ST-elevation in V1 - V3 II III avl avf V1 V2 Syncope and sudden cardiac death due to polymorphic VT Up to 50% of deaths in pts without structural heart disease men > women (8:1) V1 V4 V3 8:10 ratio of deadly vs nonlethal events (LQTS 8:60 ratio) More prevalent in South Asia V2 V5 ~ 20% SCN5A mutations V3 V6

5 Brugada Syndrome ST-elevation in V1 - V3 Syncope and sudden cardiac death due to polymorphic VT Up to 50% of deaths in pts without structural heart disease men > women (8:1) 8:10 ratio of deadly vs nonlethal events (LQTS 8:60 ratio) More prevalent in South Asia ~ 20% SCN5A mutations

6 Brugada Syndrome ST-elevation in V1 - V3 Syncope and sudden cardiac death due to polymorphic VT Up to 50% of deaths in pts without structural heart disease men > women (8:1) 8:10 ratio of deadly vs nonlethal events (LQTS 8:60 ratio) More prevalent in South Asia ~ 20% SCN5A mutations

7 Brugada Syndrome I avr ST-elevation in V1 - V3 II III avl avf V1 V2 Syncope and sudden cardiac death due to polymorphic VT Up to 50% of deaths in pts without structural heart disease men > women (8:1) V1 V4 V3 8:10 ratio of deadly vs nonlethal events (LQTS 8:60 ratio) More prevalent in South Asia V2 V5 ~ 20% SCN5A mutation V3 V6

8 Prevalence-Estimations Brugada-ECG or Brugada-Sign Asian: 1:1000 (Denjoy et al, 2007) Caucasian: 5:1000 (Napolitano et al, 2006) Japanese: 14:1000 (Napolitano et al, 2006) Asia: 3.2 million Japan: Germany:

9 Brugada Syndrome Nishizaki et al., Circulation Journal 2010

10 (Class II a) (Class II a) (Class I) (Class I) (Class II a) Antzelevitch et al., Circulation 2005; 111:

11 (Class II a) (Class II a) (Class I) (Class I) (Class II a) Antzelevitch et al., Circulation 2005; 111:

12 Scientific publications on Brugada Syndrome It is time for a new consensus paper! n= 553 n= 1065 modified from Brugada et al., Hellenic J Cardiol 2009

13 Widespread use of prophylactic ICD is associated with intolerably high rates of complications Much longer survival of BS pts as compared to ICD pts with structural heart disease Sacher et al., Circ 2006 Rosso et al., Isr Med Assoc J 2008 J Cardiovasc Electrophysiol 2011

14 Asymptomatic individuals with an arrhythmic event during follow-up in different publications 3% 0.8% 1998 Paul et al., Eur Heart J 2007; 28:

15 Asymptomatic individuals with an arrhythmic event during follow-up in different publications 3% 0.8% Paul et al., Eur Heart J 2007; 28:

16 Asymptomatic individuals with an arrhythmic event during follow-up in different publications 3% 0.8%

17 Brugada et al., Circulation 2003

18 Mean follow-up: months: n=9 VT/VF events!! VT/VF inducibility without predictive value!!! asymptomatic syncope SCD p=0.05 p=0.006 p=ns Non-inducible Inducible Eckardt et al., Circulation 2005

19 n=9 VT/VF events during follow-up EP in all 9 pts - n=5 inducible (2 with one; 3 with 2 extra beats) - n=3 with a coupling interval < 200ms PVS 3 2 Extras sensitivity (%) specificity (%) I II III V1 V2 V3 positive predictive value (%) negative predictive value (%) Eckardt et al., Circulation 2005

20 Viskin and Rosso, JACC 2011 Outcomes of Patients With Asymptomatic Brugada Syndrome It can be concluded from these data incl. 95% confidence intervals that: - the risk for spontaneous VF at 4 to 5 years follow-up is likely between 1 and 6 % for asymptomatic individuals and inducible VF and -between 1% and 4% for asympt. pts and negative EPS - long term risk?? Kamakura et al., Circ EP 2009 Probst et al., Circ 2010

21 Brugada Syndrome risk stratification History of VF/VT or syncope Male Gender?? but 70% of asymp. are male (FINGER) Family History Mutation Spontaneous type 1 (coved type) ECG But high variability But not found in large Japanese registry Late potentials Early repola. pattern inferolat. leads ST elevation during recovery of exercise But test failed to indentify 68% of SCD QRS fragmentation in V1-V3 YES Perhaps Probably not Probably not Probably Perhaps Perhaps Perhaps Perhaps

22 Morita et al., Circ 2008

23 Nademanee et al., Circ 2011

24 Nademanee et al., Circ 2011

25 Circ 2004 Zhou et al., J Cardiovasc Dis Res, 2011

26 Risk vs Benefit of quinidine Quinidine often causes side effects (e.g. diarrhea) 1 of 3 discontinues drug? Low dose quinidine Proarrhythmia (aquired LQTS) close monitoring required!! Viscin et al., Heart Rhythm 2009

27 Subcutaneous-ICD 78,2 x 68,5 x 15,7 mm Volume: 70 cm³ Weight: 145 g Duration: ~ 5 yrs Maximal energy: 80 J Post-shock pacing 1 or 2 zones bpm

28 Primary ICD prophylaxis in Brugada syndrome Syncope in the presence of Brugada ECG (IIA) Asymptomatic pts with a Brugada-ECG have a relatively low arrhythmogenic risk The accidental finding of a Brugada -ECG alone does not jusitfy ICD-implantation Programmed ventricular stimulation is of limited value for risk stratification (IIB) ACC/AHA/ESC Practice Guidelines Prevention of SCD 2006

29 Tailored treatment of Brugada syndrome The ICD is the only proven effective therapy for secondary prophylaxis of SCD Treatment of asymptomtic individuals remains difficult Open discussion No therapy Quinidine Ablation S-ICD { whether this would substitute for an ICD remains unknown

30 Yann Arthus-Bertrand DIE ERDE VON OBEN Thank YOU

31 BSPM 120 Elektroden gleichmäßig auf dem Thorax verteilt 120 unipolare Elektrogramme mit Wilson s Zentrum als Referenz Ableitungen mit ST Hebungen > 0.2mV wurden automatisch analysiert Körperoberfläche wird aus diesen Abl. und definiertem Elektrodenabstand (horizontal/vertikal) bestimmt V1 V2 V3 V4 V5 V6 Bruns & Eckardt et al., Cardiovasc Res 2002; 54:58-66

32 Body surface potential map (BSPM) beim Brugada Syndrom the area with ST-elevation 0.2mV Area size: 257 cm 2 Eckardt et al., J Cardiovasc Electrophysiol 2003: 13:

33 Body surface area of ST-elevation >0.2mm Body surface potential map (BSPM) beim Brugada Syndrom p= not inducible inducible VT Area size: 257 cm 2 Eckardt et al., J Cardiovasc Electrophysiol 2003: 13:

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