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 Beirut, Liban

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

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

Huikuri et al. NEJM 2001

Implantable Defibrillator

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

Secondary Prevention Primary Prevention

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

Summary of 2 0 Prevention Trials AVID N = Hazard ratio ICD better 1.8 Other features CASH 2000 N = 191 Aborted cardiac arrest CIDS 2000 N = Aborted cardiac arrest or syncope Trial Name, Pub Year 0.83 Aborted cardiac arrest HR:0.73 (0.59,0.89) p = Meta ● ● ● ●

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)

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

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

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

StudyMADIT IIDEFINITESCD HeFT Sponsor GuidantSt Jude MIH/Wyeth/Medtronic Reported in NEJM Mar 2002May 2004Jan 2005 No of patients Disease MICM/CHFCHF NYHA I/II/III/IV 37/34.5/24/ /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 Major ICD Secondary Prevention Trials

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, ………

LVEF < 25 ≥ Defibrillator Better MADIT II ≤ 30 Conventional Better Major ICD 1 0 Prevention Trials and LVEF > SCDHeFT  ≤ 30 LVEF  20 < 20 DEFINITE  LVEF 148

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

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

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-ischaemic SCD HeFT COMPANION (ACM only) ICD better ICD not better

ICD Recommendation: ≥40 days post MI Annual mortality rate, % Probability of Survival Defibrillator Conventional 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

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

NYHA Functional Class NYHA class, %MADIT IIDEFINITESCD HeFT I II III NYHAn I461  I 771 I99 II263 III96 II1160 III516 ICD better ICD not better MADIT II DEFINITE SCD HeFT

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)

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

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)

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

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 update 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

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 update 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

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 update 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

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

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