ICD临床试验及2008指南

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1、,ICD大型临床试验及适应证,院外存活率1%,如何救治99%的患者?,SCD,SCD,SCD,SCD,SCD,SCD,SCD,SCD,SCD,SCD,二级预防,一级预防,心脏性猝死的预防,心脏性猝死的预防,二级预防 对已发生过心脏骤停的患者实施预防一级预防 对未发生过心脏骤停的高危人群实施预防,80,85,2000,90,95,AVID,CASH,CIDS,SCD-HeFT,MADIT-II,MUSTT,MADIT,二级,二级预防,一级预防,ICD大型临床试验,SCD二级预防的临床试验,CASHCIDSAVID,与心脏骤停有关的试验,CIDS,Canadian Implantable Defi

2、brillater Study加拿大ICD研究,CIDS背景,1990-1998年主要终点为总死亡率比较ICD与胺碘酮治疗效果的多中心随机前瞻性研究,CIDS入选标准,VF/心脏骤停幸存者持续性室速伴晕厥持续性室速150 bpm，伴晕厥前兆或心绞痛，LVEF35%不明原因的晕厥，EP可诱发持续性室速,CIDS入选情况,659位患者入选-328 ICD-331 胺碘酮,16,ICD与胺碘酮相比三年内有效降低总死亡率19.6%（p=0.072）,Connolly SJ.Presented before ACC 47th Annual Scientific Sessions,Late Breakin

3、g Clinical Trials I.March 30,1998.,CIDS结果,CASH,Cardiac Arrest Study Hamburg德国汉堡心脏骤停研究,CASH背景,1987-1998年比较发生过VT和/或VF的幸存者，应用ICD与抗心律失常药物（美托洛尔、普罗帕酮、胺碘酮）治疗的效果,CASH入选情况,346位VT和/或VF幸存者入选-99 ICD-92 胺碘酮-58 普罗帕酮-97 美托洛尔,Kuck K.Presented before ACC 47th Annual Scientific Sessions,Late Breaking Clinical Trials

4、I.March 30,1998.,Kuck K.Presented before ACC 47th Annual Scientific Sessions,Late Breaking Clinical Trials I.March 30,1998.,19.6%,12.1%,2.0%,11.0%,Mortality(%),P=0.047,P 0.001,0,2,4,6,8,10,12,14,16,18,20,All-Cause,Sudden Death,ICD,胺碘酮和美托洛尔,CASH结果,CASH结果,普罗帕酮组因死亡率大大高于ICD组（29与12，=0.012），故该组于1992年提前终止试

5、验平均随访两年，ICD组的总死亡率与抗心律失常药物（美托洛尔和胺碘酮）组相比，降低37ICD组猝死发生率亦明显低于药物组,Kuck K.Presented before ACC 47th Annual Scientific Sessions,Late Breaking Clinical Trials I.March 30,1998.,AVID,Antiarrhythmics Versus Implantable Defibrillators抗心律失常药物与ICD,AVID背景,第一个大规模前瞻性随机试验比较抗心律失常药物与ICD对致命的室性心律失常患者的治疗效果1993年6月1日 试验开始19

6、97年4月7日 提前终止1016位患者入选,AVID Investigators.Am J Cardiol.1995;75:470-475.,AVID入选标准,VFVT伴晕厥VT不伴晕厥、EF 40%、SBP 80 mmHg、胸痛，或接近晕厥,AVID Investigators.N Engl J Med.1997;337(22):1576-1583.,AVID结果,AVID Investigators.N Engl J Med.1997;337(22):1576-1583.,Defibrillator Group,AA Group,Patients at Risk,104,333,644,1

7、,016,p 0.02,AVID结论,AVID Investigators.N Engl J Med.1997;337(22):1576-1583.,对有致命的室性心律失常的患者，ICD的治疗效果显著优于抗心律失常药物 对于这些患者，ICD应作为一线治疗,SCD一级预防的临床试验,MADIT MUSTT MADIT-II,与心肌梗塞后高危患者有关的试验,MADIT,Multicenter Automatic Defibrillator Implantation Trial多中心ICD临床试验,MADIT背景,心脏性猝死的第一个一级预防前瞻性试验1991-1996年32个医学中心参加（30个在美

8、国、2个在欧洲）研究目的：比较心肌梗死后有恶性室性心律失常的高危患者预防性植入ICD和传统药物治疗对死亡率的影响主要终点：总死亡率,Moss AJ.N Engl J Med.1996;335:1933-1940.,MADIT入选标准,以往发生过有Q波的心肌梗死非持续性室速发作史EF 3周无CABG和PTCA的适应证,Moss AJ.N Engl J Med.1996;335:1933-1940.,MADIT结果,1.0,0.8,0.6,0.4,0.2,0.0,0,1,2,3,4,5,Year,Probability of survival,Conventionaltherapy,Defibri

9、llator,No.of patientsDefibrillator 95 80 53 31 17 3Conventional 101 67 48 29 17 0,MADIT结论,ICD治疗组与药物治疗组相比，总死亡率降低54在心肌梗塞后高危患者组，ICD作为预防性治疗与抗心律失常药物治疗相比，可显著降低总死亡率,MUSTT,Multicenter UnSustained Tachycardia Trial多中心非持续性室速试验,MUSTT背景,1993-1999年85个美国和加拿大的医疗中心704位患者入选,MUSTT入选标准,冠心病EF 3 beats，100 bpm)电生理检查诱发VT,

10、MUSTT 5年随访结果,No EP-Guided AA Rx,EP-Guided RxTotal,EP-Guided RxICD,EP-Guided RxNo ICD,%Patients,48%,42%,24%,55%,32%,25%,9%,37%,Buxton AE.N Engl J Med.1999;341:1882-90.,MUSTT结论,CAD、无症状的NSVT、EF 40%、且EP可诱发VT的患者，ICD 治疗可明显降低心律失常性死亡或心脏骤停(降低73%-76%)及总死亡率(下降55%-60%)EP指导下的抗心律失常药物治疗不能改善患者生存率,Buxton AE.N Engl J

11、 Med.1999;341:1882-90.,MADIT-II,Multicenter Automatic Defibrillator Implantation Trial-II多中心ICD临床试验-II,MADIT-II背景,71个美国医学中心5个欧洲医学中心1998年1月试验开始2001年11月提前结束1232位患者入选试验目的：观察ICD是否能降低心肌梗塞后心功能不全患者的总死亡率,MADIT-II入选标准,急性心肌梗塞 4周LVEF 21岁,MADIT-II结果,MADIT-II于2001年11月20日提前结束平均随访 23个月,Moss AJ.N Engl J Med.2002;34

12、6:877-83.,MADIT-II结果,Hazard Ratio=0.69(p=0.016),31%Relative Reduction,N=490,N=742,MADIT-II结果,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,0,1,2,3,4,Year,No.At RiskDefibrillator 742 502(0.91)274(0.94)110(0.78)9Conventional 49

13、0 329(0.90)170(0.78)65(0.69)3,MADIT-II结论,ICD可有效降低心肌梗塞后心功能不全患者（EF 30%）的总死亡率 与以往临床试验不同的是入选患者无室性心动过速病史或需电生理检查诱发持续性室心动过速,SCD一级预防的临床试验,SCD-HeFT,与心衰高危患者有关的试验,SCD-HeFT,Sudden Cardiac Death in Heart Failure Trial心力衰竭患者心脏性猝死研究,SCD-HeFT背景,148个中心位于美国、加拿大和新西兰 2521位患者入选,SCD-HeFT背景,第一位患者入选：1997-9-16入选结束：2001-7-19

14、随访结束：2003-10-31数据统计结束：2004-3-1首次公布结果：2004-3-8 ACC会议,SCD-HeFT入选方案,SCD-HeFT入选方案,入选标准,ICD n=829,平均随访40 个月,优化：B、ACE-I、利尿剂,Bardy GH.Chapter Excerpt from Arrhythmia Treatment and Therapy.Woosley RL,Singh SN,editors.Marcel Dekker,1st edition.2000;323-42.SCD-HeFT Investigators Meeting,August 2001,data from

15、most recent follow-up,SCD-HeFT基础用药,开始 最后随访_ACEI 85%72%ACEI或ARB 96%87%-受体阻滞剂 69%78%安体舒通 19%31%襻利尿剂 82%80%阿斯匹林 56%55%他汀类 38%47%,SCD-HeFT结果,SCD-HeFT结论,NYHA II-III级，EF 35%且有良好药物治疗的患者，5年内安慰剂组的总死亡率达到7.2%/年ICD有效减少23%的总死亡率胺碘酮作为主要预防药物，不增加生存率,ICD与抗心律失常药物治疗在降低总死亡率方面的对照,1 The AVID Investigators.N Engl J Med.199

16、7;337:1576-1583.2 Kuck,et al.Circulation.2000;102:748-754.3 Connolly,et al.Circulation.2000;101:1247-1302.,4 Moss AJ.N Engl J Med.1996;335:1933-1940.5 Buxton AE.N Engl J Med.1999;341:1882-1890.6 Moss.Investor Conference Call.November 27,2001.,总 结,CIDS、CASH和AVID试验表明，与抗心律失常药物相比，ICD 能明确改善VT/VF患者生存率，而抗心

17、律失常药物并不能改善这些患者的生存率MADIT、MADIT-II试验表明对心梗后有VT的高危患者预防性植入ICD 能明确改善患者生存率MUSTT试验表明对有冠心病、低EF、无症状的非持续性VT患者，ICD能明确改善其生存率，而EP指导下的药物治疗无效SCD-HeFT研究表明ICD有效降低心衰患者的死亡率,ACC/AHA/HRS 2008 心律失常器械治疗建议ICD-部分,May 2008,ICD 治疗建议,所有SCD一级预防病人植入ICD必须建立在最佳药物治疗基础之上，并良好的生活质量下预计生存时间在一年以上。,ICD 一类治疗建议（二级预防）,非可逆性原因导致的室颤或者血流动力学不稳定的持续

18、性室速造成的心脏性骤停伴有器质性心脏病的自发性持续性室速，无论血液动力学稳定或者不稳定.晕厥原因不确定，但心脏电生理检查能够诱发出临床相关的、具有明显血流动力学障碍的持续性室速或者室颤.,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year

19、.,AVIDCASHCIDS,CIDS和AVID注册登记标准,Link研究1,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.,ICD 一类治疗建议（一级预防）,心肌梗死后40天，纽约心功能在II 级或 III 级，LVEF小于35%

20、.EF值35%,纽约心功能在II 级或 III 级的 非缺血性心肌病患者.LVEF小于 30%,纽约心功能I 级，心梗后40天，左室功能不良的患者.（原为 II a 类，现为 I 类）陈旧性心梗，LVEF小于 40%，非持续性室速，电生理检查可诱发室颤或者持续性室速.,MADIT-II,MUSTT,SCD-HeFT,MADIT II+,SCD-HeFT,不明原因的昏厥，伴有明显左室功能障碍和非缺血性扩张性心肌病心室功能正常或接近正常的持续性室速肥厚性心肌病，有一项以上主要SCD危险因素有一项以上心脏性猝死主要危险因素，心律失常性右心室发育不良或心肌病患者的心脏性猝死的预防服用受体阻止剂时出现昏

21、厥和（或）室速的长QT综合症,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.See Section 3.2.4,“Hypertrophic Cardiomyopathy,”in the full-text guidelines fo

22、r definition of major risk factors.,ICD II a 类治疗建议,正等待心脏移植的患者有晕厥发病史的Brugada综合症患者 证实室速但没有导致心脏骤停的Brugada综合症患者接受受体阻滞剂时发生昏厥和（或）室速，儿茶酚胺敏感性多形性室性心动过速心脏结节病，巨细胞性心肌炎，或恰加斯病的患者,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable exp

23、ectation of survival with good functional capacity for more than 1 year.,ICD II a 类治疗建议,LVEF 35%，心功能分级I级的非缺血性扩张性心脏病QT间期延长综合症，有心脏性猝死危险因素有晕厥和严重器质性心脏病，侵入性和非侵入性检查不能明确原因 有猝死史的家族性心肌病患者 左室心肌致密化不全的患者,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical ther

24、apy and have reasonable expectation of survival with good functional capacity for more than 1 year.,ICD II b 类治疗建议,即使符合上述I、IIa和IIb类适应症，但预期寿命短于1年 无休止的室速或者室颤 有明显的精神疾病，可能被器械植入术加重，或是不能进行系统的随访药物难以控制的心力衰竭，NYHA心功能IV，无条件进行心脏移植或CRT-D治疗,All primary SCD prevention ICD recommendations apply only to patients who

25、 are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.,ICD III 类治疗建议,原因不明的昏厥，即没有可诱发的室性快速心律失常也不合并器质性心脏病 合并沃尔夫-帕金森-怀特综合症引起的房性心率失常、右室或左室流出道性室速，特发性室速，无器质性心脏病分支相关性室速，经手术或导管消融术可以治愈者无器质性心脏病，由完全可逆原因导致的室性快速型心律失常（如电解质紊乱，药物，外伤）,All

26、 primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.,ICD III 类治疗建议,ICD 在儿科患者和先天性心脏病患者中的治疗建议 I 类,病因明确并且排除其他可逆原因的心脏骤停患者血流动力学和电生理检查评估存在症状性持续性室速的先天性心脏病患

27、者，部分患者可以考虑导管消融术或手术修补,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.,原因不明的反复晕厥，伴心室功能异常或电生理检查诱发室性心律失常的先天性心脏病患者复杂先天性心脏病，反复晕厥伴严重心室功能障碍，侵入性和非侵入性

28、检查不能明确原因者 所有“ICD应用建议”中的III类适应症同样适用于儿童和成人先天性心脏病患者,All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.,ICD 在儿科患者和先天性心脏病患者中的治疗建议 II a 类 II b 类 III

29、类,预防SCD 主要的ICD 临床试验,*Hazard ratios for death from any cause in the ICD group compared with the non-ICD group.Includes only ICD and amiodarone patients from CASH.CI Upper Bound 1.112 CI indicates Confidence Interval,NS=Not statistically significant,NSVT=nonsustained ventricular tachycardia,SAECG=sign

30、al-averaged electrocardiogram.Epstein A,et al.ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities.J Am Coll Cardiol 2008;51:e162.Table 5.,Notable Changes in 2008 ACC/AHA/HRS Guidelines,ICD recommendations are combined into a single list because of overlap between pri

31、mary and secondary indications.Primary prevention ICD indications in nonischemic cardiomyopathy are clarified using data from SCD-HeFT(i.e.,ischemic and nonischemic cardiomyopathies and LVEF 35%,NYHA II-III)for support.Indications for ICD therapy in inherited arrhythmia syndromes and selected nonisc

32、hemic cardiomyopathies are listed.MADIT II indication(i.e.,ischemic cardiomypathy and LVEF 30%,NYHA I)is now Class I,elevated from Class IIa.EF criteria for primary prevention ICD indications are based on entry criteria for trials on which the recommendations are based.The need for optimization of m

33、edical therapy before CRT implantation is emphasized.Independent risk assessment preceding ICD implantation is emphasized,including consideration of patient preference.Optimization of pacemaker programming to minimize unneeded RV pacing is encouraged.Pacemaker insertion is discouraged for asymptomat

34、ic bradycardia,particularly at night.A section has been added that addresses ICD and pacemaker programming at end of life.Emphasized primary SCD prevention ICD recommendations apply only to patients receiving optimal medical therapy and reasonable expectation of survival with good functional capacity for 1 year.,