心源性猝死的预防和治疗

Sudden Cardiac Death: Prevention and Treatment Lexin Wang, M.D., Ph.D. Professor of Clinical Pharmacology Head, Cardiovascular Research Incidence of SCD SCD (caused by sudden cardiac arrest) is the most common cause of death in Western societies Incidence: 300,000 to 400,000 each year (U.S.) only 2% 15% reach the hospital Half of these early survivors die before discharge Risk Factors of SCD Left ventricular failure CHD, cardiomyopathy Sudden cardiac death syndromes Long QT syndromes Brugada syndrome Polymorphic catecholaminergic VT Isolated ventricular fibrillation CAD has become a main cause of SCD 80% CAD 15% cardiomyopathy 5% other* Huikuri HV. N Engl J Med. 2001;345:1473-1482. Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 6th ed. W.B. Saunders, Co. 2001. *ion-channel abnormalities, valvular or congenital heart disease, other causes Bays de Luna A. Am Heart J. 1989;117:151-159. Bradycardia 17% Monomorphic VT 62%Primary VF 8% TdP 13% Prevalence of arrhythmia at SCDPrevalence of arrhythmia at SCD Heart Failure and SCD More than one million new heart failure patients every year in the USA 25% mortality in 2.5 years in moderate to severe CHF A total of 15% of CHF patients die of SCD Gorgels, PMA. Eur Heart J .2003;24:1204-1209. LVEF % SCD Victims 7.5% 5.1% 2.8% 1.4% LVEF and SCD Causes of deaths in HF: mainly SCD in NYHA II-III, heart failure in NYHA IV MERIT-HFStudy Group. LANCET. 1999;353:2001-2007. NYHA Class III n = 103 NYHA Class II n = 103 NYHA Class IV n = 27 64% 12% 24% 11% 56% 33% 59% 15% 26% Myocardial infarction and SCD Acute phase: ischemia-provoked VF; or mechanical dysfunctions (e.g. ventricular or papillary rupture) Chronic phase: structural remodelling of the LV, leading to re-entry or heart failure Risk stratification of SCD Risk assessment Clinical data Aetiology; family history; LVEF EPS T wave alternans QT dispersion Arrhythmia during Holter monitoring or stress test Ideka T, et al JACC 2006; 48:2268 Sensitivity SpecificityPPV NPV PA Microvolt -TWA83%83%9%99.6%83% Nonsustained VT 44%83%7%98.8%88% Ventricular late potentials 35%91%7%98.6%90% Predictive values of positive TWA, nonsustained VT and ventricular Late potentials So what we do? The most important criterion is reduced left ventricular function LVEF 4 weeks); left ventricular EF 21 years Patients randomly assigned in a 3:2 ratio to receive ICD or conventional medical therapy MADIT-II Trial started July 8, 1997 Trial stopped prematurely in November 20, 2001 because ICD saved lives 1,232 patients enrolled from 76 centers in U.S. and Europe MADITT II- Mortality CONV DEFIB (n=490) (n=742) Deaths 97 19.8% 105 14.2% - Hazard Ratio (ICD:CONV)0.69 (31% mortality) (95% CI) (0.51, 0.93) P-value 0.016 MADIT-II Moss AJ. N Engl J Med. 2002;346:877-83. Defibrillator Conventional P = 0.007 1.0 0.9 0.8 0.7 0.6 0.0 Probability of Survival 01234 Year No. At Risk Defibrillator 742502 (0.91)274 (0.94)110 (0.78)9 Conventional 490329 (0.90)170 (0.78) 65 (0.69)3 SCD-HeFT Sudden Cardiac Death in Heart Failure Trial (SCD- HeFT) NYHA class 2-3 HF and LVEF 35% Largest internal- cardioverter-defibrillator (ICD) trial ever conducted ICD vs placebo Median follow-up of 45 months SCD- HeFT Bardy et al. N Eng J Med 2005; 352 (3): 225 SCD-HeFT: All-cause mortality All-cause mortality ICD Amiodarone Placebo 3 years 17.1% 24.0% 22.3% 5 years 28.9% 34.1% 35.8% Jared Bunch T, et al. Circulation 2007;115:2451-57 Jared Bunch T, et al. Circulation 2007;115:2451-57 Summary Most SCD are due to coronary artery disease and heart failure LVEF is the most reliable non-invasive predictor for SCD SCD under 30 years of age is usually due to inherited heart disease Summary Anti-arrhythmic drugs to prevent sudden death are not as important as once thought -blockers are more effective than amiodarone or sotalol in pts with CHF or CHD Summary ICD is the most effective prevention for SCD Prophylactic ICD therapy is ready for prime-time use in patients with CHD and CHF ICDs prolong l