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La stratificazione del rischio aritmico oltre la frazione di eiezione Milano 17 Aprile 2009 Prof. Luigi Padeletti Heart Failure & Co

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Get With The Guidelines-Heart Failure (GWTG-HF) Shah et al. J Am Coll Cardiol 2009

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Al-Khatib et al. Am Heart J 2008 Potential barriers to the dissemination of ICD therapy

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Al-Khatib et al. Am Heart J 2008 Potential barriers to the dissemination of ICD therapy

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Al-Khatib et al. Am Heart J 2008 Potential barriers to the dissemination of ICD therapy

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Beta-blocker and Amiodarone utilization can affect the outcome of ICD trials

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Cumulative Benefit of ACEI and Beta Blockers Exner DV et al. JACC; 1999; 33: 916-23 P < 0.01 P < 0.05

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Beta - Adrenergic Blocking Agents SCD - Treated pts MERIT-HF3.6% CIBIS II4% US Carvedilol1.7% MOCHA2.3% MERIT-HF Lancet 1999; 353: 2001-7 AVERAGE SD decrease 30% AVERAGE SD decrease 30%

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Outcome of recent major Beta-blocker trials Siddiqui et al Curr Opin Cardiol 2006

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Beta-Blockers to reduce sudden death in HF Adamson et al J Cardiac Fail 2006

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Beta-Blockers and ICD therapy Brodine et al. Am J Cardiol 2005

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Tung R et al. J Am Coll Cardiol 2008;52:111121 Amiodarone : not an innocent drug!

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MADIT I In the conventional-therapy group, overall mortality was slightly higher among those who were receiving amiodarone at one month than among those who were not receiving the drug (36 percent vs. 26 percent) Moss et al N Engl J Med 1996

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Guidelines for ICD implantation for the secondary And primary prevention of SCD Al-Khatib et al. Am Heart J 2008

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Meta-analysis of ICD secondary prevention trials Connolly et al Eur Heart J 2000

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Meta-analysis of ICD secondary prevention trials Connolly et al Eur Heart J 2000

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Meta-analysis of ICD secondary prevention trials Connolly et al Eur Heart J 2000 The prolongation of life by the ICD over amiodarone was 2.1 months at 3 years of follow-up and 4.4 months at 6 years

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Al-Khatib et al. Am Heart J 2008 Guidelines for ICD implantation for the secondary And primary prevention of SCD

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The optimal timing of defibrillator insertion after myocardial infarction remains unresolved

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NEJM 352;2581

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Dinamit-trial Hohnloser et al N Engl J Med 2004

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Dinamit-trial Hohnloser et al N Engl J Med 2004

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MADIT II Specifically, 73 patients (14.9 percent) in the conventional-therapy group and 148 in the defibrillator group (19.9 percent) were hospitalized with heart failure, representing 9.4 and 11.3 patients so hospitalized per 1000 months of active follow-up, respectively (nominal p=0.09) Moss et al N Engl J Med 2002

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Aetiology in known CAD victims Nr cases224 CAD171/22477% New MI10/1716% Previous MI113/17166% Time first MI- SCA 9.77.5Years Anterior MI42/11337% Inferior MI60/1353% Previous PTCA40/17118% Previous CABG50/17120% Gorgeles et al Eur Heart J 2003;24:1204

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Inclusion criteria:myocardial infarction one month or more before entry

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Wilber et al Circulation 2004;109:1082 * * p 0.02 for HR Time Dependence of Mortality Risk and Defribrillator Benefit After Myocardial Infarction

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MADIT II Inclusion/Exclusion Criteria Exclusion criteria Previous cardiac arrest Sustained VT NYHA Class IV CABG or PTCA < 3 months CABG or PTCA planned Life-threatening diseases < 21 years Inclusion criteria MI > 4 weeks LVEF < 30% > 21 years

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Al-Khatib et al J Cardiovasc Electrophysiol 2008 PCI in SCD-Heft

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Al-Khatib et al J Cardiovasc Electrophysiol 2008 CABG in SCD-Heft

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SCD-Heft trial Amiodarone or ICD for congestive heart failure Hohnloser et al N Engl J Med 2004

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SCD-Heft trial Amiodarone or ICD for congestive heart failure Hohnloser et al N Engl J Med 2004

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SCD-Heft trial Amiodarone or ICD for congestive heart failure Hohnloser et al N Engl J Med 2004

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ACC/AHA/ESC Guidelines EF cutoff: 2006 < 40% 2008 < 35%

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Prediction of Sudden Cardiac Death After Myocardial Infarction in the Beta-Blocking Era EF (%) 37 11 NYHA I 24% EF (%) 41 11 NYHA I 55% Huikuri et al JACC 2003;42:652

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NEJM 352;2581

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MADIT IIVALIANT

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Influence of Ejection Fraction on Cardiovascular Outcomes in a Broad Spectrum of Heart Failure Patients CHARM study Solomon et al Circulation 2005;112:3738

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SCA rate related to LV EF Gorgeles et al Eur Heart J 2003;24:1204

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SCA rate related to LV EF Gorgeles et al Eur Heart J 2003;24:1204 The prevention paradox

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Clincal Trials and Clinical Indications for ICD Bunch TJ et al Circulation 2007;115:2451

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Sugeng L et al Circulation 2006;114:654

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Ejection fraction by imaging modality: An analysis of SCD-Heft Gula et alAm Heart J 2008

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Clincal Trials and Clinical Indications for ICD Bunch TJ et al Circulation 2007;115:2451

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Buxton et al Circulation 2002;106:2466

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Clincal Trials and Clinical Indications for ICD Bunch TJ et al Circulation 2007;115:2451

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Sudden cardiac death The role of risk stratification There is currently no single test capable of accurate prediction of the SCD risk in various clinical settings and patient populations. The risk itself is nonlinear and changes dynamically with the progression of disease and therapies applied. Kusmirck and Gold Am Heart J 2007;153:S252S33

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Amiodarone Trials Meta-Analysis on 6553 Pts Lancet 1997; 350:1417-24 The most potent single predictor of arrhythmic/sudden death was the presence of symptomatic CHF (NYHA class III - IV) of symptomatic CHF (NYHA class III - IV) which carried a 12,2% annual risk of arrhythmic/sudden compared to 5.0% for arrhythmic/sudden compared to 5.0% for those without symptoms. The most potent single predictor of arrhythmic/sudden death was the presence of symptomatic CHF (NYHA class III - IV) of symptomatic CHF (NYHA class III - IV) which carried a 12,2% annual risk of arrhythmic/sudden compared to 5.0% for arrhythmic/sudden compared to 5.0% for those without symptoms.

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The problem is that trials were designed to demonstrate that the ICD reduces mortality in selected populations; they were not designed to test how best to use the ICD. That is the task before us. Buxton 2005