CRT-D CRT-D 在心衰患者猝死在心衰患者猝死防治中的价值防治中的价值哈尔滨医科大学附属第二医院哈尔滨医科大学附属第二医院心血管病医院心血管病医院 于波于波预后比大多数肿瘤还要恶劣1 World Health Statistics, World Health Organization, 1995.1 World Health Statistics, World Health Organization, 1995.2 American Heart Association, 2002 Heart and Stroke Statistical Update.2 American Heart Association, 2002 Heart and Stroke Statistical Update.心 衰 与 猝 死21世纪的心血管流行病 CHF and AF ！2003年统计1 American Heart Association. Heart Disease and Stroke Statistics 2005 Update.2 Jemel A. CA Cancer J Clin. 2003;53:5-26.3 U.S. HIV & AIDS Statistic Summary. Avert.org.美国SCA发病情况Breast Cancer2335,000SCA318,00040,000152,200163,000AIDS3Lung Cancer2Stroke1在美国，每年SCA 的发病人数超过所有这些疾病的总和目前美国 CHF 状况约有 500万 CHF，每年新发病例约 55万CHF是老年人最主要的心血管住院原因尽管药物治疗取得显著进展，25%的心衰患者在诊断后2.5 年内死亡，其中50%为猝死VT/VFSCA一旦发生，存活率非常低1%，已成为严重的公众健康问题1 American Heart Association. Heart Disease and Stroke Statistics 2005 Update.2 NHLBI, CHF Data Fact Sheet, September 1996.3 Sweeney MO. PACE. 2001;24:871-888.4 SOLVD Investigators. N Engl J Med 1992;327:685-6915 SOLVD Investigators. N Engl J Med 1991;325:293-302.6 Goldman S. Circulation 1993;87:V124-V131中国人口基数大，每年SCA的发病人数超过54万心衰病人心脏性猝死的危险性心力衰竭和猝死在 Framingham 心脏研究39年的随访中, 无论男性还是女性，CHF 的出现明显增加心脏性猝死和全因死亡.11 Redrawn from Kannel WB, Wilson PWF, DAgostino RB, Cobb J. Sudden coronary death in women. Am Heart J 1998 Aug; 136: 205-212心衰的出现增加60-115%猝死特殊人群SCD的发生率和年SCD发生人数Adapted from: Myerburg RJ. Sudden Cardiac Death: Exploring the Limits of Our Knowledge. J Cardiovasc Electrophysiol Vol. 12, pp. 369-381, March 2001. 300,000200,000100,0000Incidence of Sudden Deaths Per Year (number)Multiple risk subgroupsPatients with any previous coronary eventPatients with ejectionfraction 35% or CHFCardiac arrest, VT/VF survivorsHigh-risk post-MI subgroupsGeneral adult population3025201050Incidence of Sudden Death(% of group)MADIT, MUSTT, MADIT IIAVID, CASH, CIDSSCD-HeFT1 Gorgels, PMA Out-of-hospital cardiac arrest-the relevance of heart failure.The Maastricht Circulatory Arrest Registry.European Heart Journal.2003;24:1204-1209.LVEF% SCA Victims7.5%5.1%2.8%1.4%LVEF与SCA的相关性SCA危险性增加了6+ 倍CHF左室功能不全患者SCD的发生率总死亡率 15-40%；SCD占总死亡的 50%.12 months16 months41.4 months27 months 13 months45 months6 monthsControl Group Mortality %在诊断为心衰的患者中，猝死的危险是普通人群的69倍 American Heart Association. Heart Disease and Stroke Statistics 2005 Update. 心衰患者SCD的预防及治疗尽管给予理想的药物治疗，心衰的猝死率仍非常高1 MERIT-HF Study Group.Effect of metroprolol CR/XL in chronic heart failure.Lancet.1999;353:2001-2007.2 CIBIS Investigations and Committees.The cardiac insufficiency bisprolol study II (CIBIS-II).Lancet.1999;353:9-13.3 Packer M,Bristow MR,Cohn JN,et al.The effect of carvedilol on morbitity and nortality in patients with chronic heart Heart Failure Study Group.N Engl J Med.1996;334:1349-1355.4 The RALE Investigators.Effectiveness of spironolactone added to an aniotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure(the Randomized Aldactone Evaluation StudyRALES.Am J Cardiol.1997;78:902.CRT治疗随机临床试验进展累计图CRT与单纯药物治疗比较在合理药物治疗的根底上,CRT治疗能显著减轻心衰病症，改善心功能和生活质量可显著降低心衰病人全原因死亡率或主要心血管原因住院的联合终点达37%可进一步降低心衰患者全原因死亡率达36% CRT治疗使心衰恶化死亡和猝死均有所下降，反映了心功能改善带来的益处不同程度心衰的死亡原因1 MERIT-HFStudy Group. Effect of Metoprolol CR/XL in chronic heart failure:Metoprolol CR/XL randomized intervention trial in congestive heart failure(MERIT-HF).LANCET. 1999;353:2001-2007.NYHA Class III n = 103NYHA Class II n = 103NYHA Class IV n = 2764%12%24%11%56%33%59%15%26%MERIT-HF研究死亡模式分研究死亡模式分析发现析发现,NYHA II/III级患者的级患者的主要死因为主要死因为SCA，而，而NYHA IV级的患者大多死于心衰级的患者大多死于心衰心衰猝死的ICD治疗Buxton AE. N Engl J Med. 1999;341:1882-90.Time after Enrollment (Years)00.10.20.30.40.50.6心律失常死亡和心脏骤停发生率123450p 0.001EP-指导的抗心律失常药物治疗没有抗心律失常药物治疗EP-指导的ICD治疗MUSTT MI, EF 4 周, LVEF 30%Moss AJ. N Engl J Med. 2002;346:877-83.除颤器组传统组P = 0.0070.90.80.70.60.0生存率01234YearNo. At Risk除颤器组 742502 (0.91)274 (0.94)110 (0.78)9传统组 490329 (0.90)170 (0.78) 65 (0.69)3传统组2年死亡率25%0.40.30.20.10Mortality06121824303642485460Months of follow-upAmiodaroneICD TherapyPlaceboHR97.5% ClP-ValueAmiodarone vs. Placebo1.060.86, 1.300.529ICD Therapy vs. Placebo0.770.62, 0.960.007SCD-HeFT SCD-HeFT SCD-HeFT SCD-HeFT NYHA II/III(NYHA II/III(缺血或非缺血缺血或非缺血),LVEF35%),LVEF35%DEFINITE试验Hazard Ratio (95% CI) ICD vs. OMTP-ValueReduction in Death w/ICD全因死亡 (All Pts)0.65 (0.40 - 1.06)0.0835%全因死亡 (NYHA Class III)0.37 (0.15 - 0.90)0.0263%心律失常所致猝死0.20 (0.06 - 0.71)0.00680%非缺血性DCM(LVEF18岁NYHA III/IV,需要襻利尿剂治疗的心衰至少持续6周已接受标准药物治疗LVEF=30mm/m除以身高参数)QRS=120ms如果患者QRS 在120ms与149ms之间，那么需满足以下3条心脏收缩不同步标准中的两条：主动脉射血前间期延迟140ms心室间机械延迟40ms左室后外侧壁冲动延迟一级终点( (所有原因死亡率或心血管住院率联合终点所有原因死亡率或心血管住院率联合终点) )1.00CRT : 159 pts (39%)348118232292404Medical Therapy768166273323409CRTNumber at risk0500100015000.000.250.500.75HR 0.63 (95% CI 0.51 to 0.77)Event-free SurvivalDaysP .0001Medical : 224 ptsTherapy (55 %)心脏再同步治疗与对照组相比使所有原因死心脏再同步治疗与对照组相比使所有原因死亡率或心血管病因住院联合终点下降亡率或心血管病因住院联合终点下降37%37%CARE-HF Extension StudyTime to Sudden DeathCRTMedicalTherapy016000.000.250.500.751.00SurvivalTime (days)4008001200CRT = 32 sudden deaths (7.8%)Medical Therapy = 54 sudden deaths (13.4%)Hazard Ratio 0.54 (95% CI 0.35 to 0.84; P=0.006)Main Study 平均随访时间：29.4mExtension Study 平均随访时间：37.6mMain Study：CRT = 29 sudden deaths 7.1%Medical Therapy = 38 sudden deaths (9.4%两年的随访中两条曲线趋势一致CARE-HF, COMPANION等研究进一步证明了CRT 在标准药物治疗的根底上，或较单纯的药物治疗能够降低死亡率和住院率，CRT-D能进一步降低高危患者的死亡率COMPANION试验：CRT-D较CRT-P可以更进一步改善患者预后CRT-D治疗可通过逆转重构，减少恶性室性心律失常的发生，减少ICD放电CRT-D对猝死风险较大患者可以带来更大益处，是最正确治疗方案CRT及CRT-D临床研究进展 目前认为，符合CRT适应证，同时又是猝死的高危人群，尤其是心肌梗死后或缺血性心肌病的心功能不良患者，应尽量植入CRT-D.谢谢