1. Prevention de la Mort Subite Treatment of Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death S. Nasr, M.D. Clinical Cardiac Electrophysiologist Association Franco-Libanaise de Cardiologie 11 Mai 2007 - Beirut, Liban

2. Cause of Death % Total Mortality: Contribution from Sudden Cardiac Death Zheng et al., Circulation 2001

3. Holter recordings from 157 cases with fatal arrhythmias Brady- arrhythmias 62% 17% Bayes de Luna et al. Am Heart J 1989 VT  VF Primary VF9% 13% Torsade de Pointes Sudden Cardiac Death

4. Huikuri et al. NEJM 2001

5. Implantable Defibrillator

6. Myerburg et al., Circulation 1992 30201052103002001000 (% per year) (x 1000) IncidenceEvents per Year Adult population CAD History of a coronary event Heart failure Resuscitation with previous MI Sudden Cardiac Death

7. Secondary Prevention Primary Prevention

8. 1020304060 LV-EF (%) CIDS CASH Dutch trial AVID VF, cardiac arrest sustained VT ICD Trials - Secondary prophylaxis

9. Summary of 2 0 Prevention Trials 0.6 0.81.01.21.4 AVID 1.60.4 1997 N = 1016 0.62 Hazard ratio ICD better 1.8 Other features CASH 2000 N = 191 Aborted cardiac arrest CIDS 2000 N = 659 0.82 Aborted cardiac arrest or syncope Trial Name, Pub Year 0.83 Aborted cardiac arrest HR:0.73 (0.59,0.89) p = 0.0023 Meta ● ● ● ●

10. Recommendations for 2 0 Prevention Class I Recommendations The ICD is effective therapy to reduce mortality by a reduction in SCD in patients with LVD due to prior MI who present with hemodynamically unstable sustained VT, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: A) An ICD should be implanted in patients with non-ischemic DCM and significant LVD who have sustained VT or VF, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: A)

11. 510203040 CAT CABG-Patch MUSTT MADIT I ns VT High risk no VA MADIT II DINAMIT SCD-HeFT DEFINITE LV-EF (%) ICD Trials - Primary prophylaxis

12. ICD 1 0 Prevention Trial Results CABG-Patch MUSTT MADIT I MADIT II DINAMIT SCD-HeFT DEFINITE AMIOVIRT CAT 0 0.511.522.5 CAD, MI NICM CAD, NICM Hazard Ratio ICD betterNo ICD better

13. Risk stratification for sudden death in ICD trials  Ejection fraction (EF <30%, <35%, <40% +...)  Etiology of depressed EF (CAD vs DCM)  EP study (inducible VT, VF)  Timing of remote myocardial infarction ( 40 days / 1 month)  [HRV]  NYHA class  QRS duration

14. StudyMADIT IIDEFINITESCD HeFT Sponsor GuidantSt Jude MIH/Wyeth/Medtronic Reported in NEJM Mar 2002May 2004Jan 2005 No of patients 12324582521 Disease MICM/CHFCHF NYHA I/II/III/IV 37/34.5/24/4.521.6/57.4/21.0/……/70/30/… LVEF, %  30 (23)  35 (21)  35 (25) IHD/NIHD, % 100/……/10052/48 Device ICD 1 o end-point ACM Study duration Jul 1997 – Nov 2001July 1998 – June 2002Sep 1997 – Jul 2001 Follow-up, months 202945.5 Major ICD Secondary Prevention Trials

15. LV-EF is considered as the best parameter for risk stratification after MI exponential increase of risk of SCD below EF 35-40% LV-EF (%) risk LV-function as predictor of SCD MUSST, MADIT, MADIT-2, SCD-HeFT DINAMIT, COMPANION, ………

16. LVEF < 25 ≥ 25 23 0.2 0.4 0.6 0.8 1.0 1.2 1.4 Defibrillator Better 831 401 1232 MADIT II 15 20 25 40 35 30 ≤ 30 Conventional Better Major ICD 1 0 Prevention Trials and LVEF > 30 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1390 285 1675 SCDHeFT 15 20 25 40 35 30  35 25 ≤ 30 LVEF 0.2 0.4 0.6 0.8 1.0 1.2 1.4 310 458  20 < 20 DEFINITE  35 21 15 20 25 40 35 30 LVEF 148

17. Principle of Guidelines 40 35 30 25 Class: 1 LOE: A Class: IIa; LOE: B Class: IIb; LOE: B ABC LVEF 40 35 30 25 Class: 1 LOE: A LVEF Multiple trials with EF < 30% No trials of EF 30-35% or 35-40% EF difficult to measure

18. Examples of Guideline Recommendations 40 35 30 25 Class: 1 LOE: A LVEF Class: 1 LOE: B CHDNICM ≤ 30-40% ≤ 30-35%

19. Etiology of Heart Failure StudyMADIT IIDEFINITESCD HeFTTotal IschaemicAll (1232)N/A52% (884)2116 Non-ischaemicN/AAll (458)48% (792)1250 Aetiologyn Ischaemic884 Non-ischaemic792 Ischaemic506 Non-ischaemic397 0.20.40.60.811.21.4 SCD HeFT COMPANION (ACM only) ICD better ICD not better

20. ICD Recommendation: ≥40 days post MI 6.0 1.5 3.4 3.5 Annual mortality rate, % Probability of Survival 1.0 0.9 0.8 0.7 0.6 0.0 Defibrillator Conventional 01234 Year DINAMIT Hohnloser SH et al, 2004 MADIT II Wilber DJ et al, 2004 MADIT II Moss AJ, 2002 Salukhe TV et al, 2004 LY gained per device Mortality / 100py Life expectancy >1 y

21. Bardy G. et al., N Eng J Med 2005; 352: 225-37 SCD-HeFT NYHA IINYHA III

22. NYHA Functional Class NYHA class, %MADIT IIDEFINITESCD HeFT I3721.6- II34.557.470 III242130 NYHAn I461  I 771 I99 II263 III96 II1160 III516 ICD better ICD not better MADIT II DEFINITE SCD HeFT 00.40.81.21.622.4

23. Recommendations for 1 0 Prevention Class 1 Recommendation: ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with non-ischemic DCM who have an LVEF ≤ 30% to 35%, are NYHA functional class II or III receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: B) Class 1 Recommendation: ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with LVD due to prior MI who are at least 40 days post-MI, have an LVEF ≤ 30% to 40%, are New York Heart Association (NYHA) functional class II or III, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: A)

24. NYHA Functional Class 1 and LVD “The writing committee struggled with this issue since guidelines are meant to summarize current science and not take into account economic issues or the societal impact of making recommendations. However the committee recognizes that the economic impact and societal issues will clearly modulate how these recommendations are implemented” NYHAn I461  I 771 I99 II263 ICD better ICD not better MADIT II DEFINITE 00.40.81.21.622.4

25. NYHA Class I Recommendations Class IIa Implantation of an ICD is reasonable in patients with LVD due to prior MI who are at least 40 days post-MI, have an LVEF of ≤ 30% to 35%, are NYHA functional class I on chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: B) Class IIb Placement of an ICD might be considered in patients who have non-ischemic DCM, LVEF ≤ 30% to 35%, are NYHA functional class I receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: C)

26. Guidelines for the management of patients at risk of sudden death  ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult  ESC 2005 Guideline Update for the Diagnosis and Treatment of Chronic Heart Failure  ACC / AHA 2004 Guidelines for the management of Patients with ST-Elevation Myocardial Infarction  ACC / AHA / NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices

27. ICD Indications Group of patientsACC/AHA HFESC HF ACC/AHA STEMI ACC/AHA/ NASPE for PM and ICD ACC/A/H/A/ESC Ventricular Arrhythmias and Sudden Cardiac Death 2005 update2005200420022006 s/p MI, EF  30%, NYHA II, III Class I, LOE B Class IIb, LOE B Class IIa, LOE B Class IIa, LOE B s/p MI EF ≤ 30-40% NYHA II-III Class I LOE A s/p MI, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A Class IIa, LOE B N/A s/p MI, EF 30-40%, NSVT, positive EPS N/A Class I, LOE B Class IIb, LOE B s/p MI, EF  30%, NYHA I Class IIa, LOE B N/A s/p MI, EF ≤ 30-35% NYHA I Class IIa; LOE B NICM, EF  30%, NYHA II, III Class I, LOE B Class I, LOE A N/A LVEF ≤ 30-35% NYHA II-III Class I LOE B NICM, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A N/A NICM, EF  30%, NYHA I Class IIb, LOE C N/A EF ≤ 30-35% Class IIb; LOE B Comparison between Guidelines

28. ICD Indications Group of patientsACC/AHA HFESC HF ACC/AHA STEMI ACC/AHA/ NASPE for PM and ICD ACC/A/H/A/ESC Ventricular Arrhythmias and Sudden Cardiac Death 2005 update2005200420022006 s/p MI, EF  30%, NYHA II, III Class I, LOE B Class IIb, LOE B Class IIa, LOE B Class IIa, LOE B s/p MI EF ≤ 30-40% NYHA II-III Class I LOE A s/p MI, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A Class IIa, LOE B N/A s/p MI, EF 30-40%, NSVT, positive EPS N/A Class I, LOE B Class IIb, LOE B s/p MI, EF  30%, NYHA I Class IIa, LOE B N/A s/p MI, EF ≤ 30-35% NYHA I Class IIa; LOE B NICM, EF  30%, NYHA II, III Class I, LOE B Class I, LOE A N/A LVEF ≤ 30-35% NYHA II-III Class I LOE B NICM, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A N/A NICM, EF  30%, NYHA I Class IIb, LOE C N/A EF ≤ 30-35% Class IIb; LOE B Comparison between Guidelines

29. ICD Indications Group of patientsACC/AHA HFESC HF ACC/AHA STEMI ACC/AHA/ NASPE for PM and ICD ACC/A/H/A/ESC Ventricular Arrhythmias and Sudden Cardiac Death 2005 update2005200420022006 s/p MI, EF  30%, NYHA II, III Class I, LOE B Class IIb, LOE B Class IIa, LOE B Class IIa, LOE B s/p MI EF ≤ 30-40% NYHA II-III Class I LOE A s/p MI, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A Class IIa, LOE B N/A s/p MI, EF 30-40%, NSVT, positive EPS N/A Class I, LOE B Class IIb, LOE B s/p MI, EF  30%, NYHA I Class IIa, LOE B N/A s/p MI, EF ≤ 30-35% NYHA I Class IIa; LOE B NICM, EF  30%, NYHA II, III Class I, LOE B Class I, LOE A N/A LVEF ≤ 30-35% NYHA II-III Class I LOE B NICM, EF 30-35%, NYHA II, III Class IIa, LOE B Class I, LOE A N/A NICM, EF  30%, NYHA I Class IIb, LOE C N/A EF ≤ 30-35% Class IIb; LOE B Comparison between Guidelines

30. Summary and Conclusions VA&SCD Guidelines focus on management of actual and threatened ventricular tachyarrhythmias, and Build on others that have preceded them - some recommendations have not changed. Introduce many new and some potentially controversial recommendations Favour the ICD and extend its indications: Class I CHF / little or no LV dysfunction / wider range of ejection fraction / non-ischemic cardiomyopathy Acknowledge that not all those who might benefit from ICD therapy can accept or can receive such treatment - alternative treatment is recommended for those who do not receive an ICD

31. Guidelines and Controversy You can please all the people some of the time, and some of the people all the time, but you cannot please all the people all the time." Abraham Lincoln