缺血性及非缺血性心肌病猝死的預(yù)防

1、T. Jared Bunch MD,缺血性及非缺血性心肌病猝死的預(yù)防,Intermountain Heart Rhythm Specialists, Intermountain Medical Center,Conflicts of Interest,Boston Scientific: speakers honorarium,需要急診植入ICD人數(shù)增加,Myerberg: Circ, 1998,CP1185382-11,需要植入I

2、CD的人群OREGON SUD研究,CP1201806-4,Stecker and Chugh: 42:446A JACC, 2005 (Abstract),,%,VF/VT所致的心臟停搏后的存活率,,年齡、性別和疾病相匹配的對(duì)照組 (p=0.68),植入ICD組,U.S. 普通人群對(duì)照 (p=0.02),長(zhǎng)期存活率,Bunch TJ, White RD, NEJM, 2003,,,p-值,0.27,0.12,0.73,0.14,0

3、.19,0.07,0.65,0.01,0.33,0.19,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,,25,,50,,75,,100,,,身體因素,,精神因素,,有效性,,社會(huì)功能,,身體角色,,情感角色,,身體功能,,智力健康指數(shù),,平時(shí)健康情況,認(rèn)知,,疼痛指數(shù),,,,,,,,,,,,*,,預(yù)計(jì)惡化,,長(zhǎng)期生活質(zhì)量,Bunch TJ, White RD, NEJM, 2003,,,,,,AVID 試驗(yàn)中的存活率（

4、未經(jīng)過校正）,存活比率,高危病人1,016644333104存活率 (%) 除顫組 89.3 81.6 75.4 抗心律失常藥物組 82.

5、3 74.7 64.1,年,NEJM 337: 1576, 1997,,,P<0.02,除顫人群抗心律失常藥物治療,CP971778-41,,累計(jì)風(fēng)險(xiǎn),胺碘酮ICD,高風(fēng)險(xiǎn)患者胺碘酮 33130428524020417315212389ICD32830528824521517915313410

6、1D313511611112,隨機(jī)分組后觀察的時(shí)間,1p=0.0722p=0.14,,,加拿大可植入性除顫器存活率研究的分析 (CIDS)存活率分析:全因死亡率,,,CP971778-18,高?；颊呓M缺血性心臟病,14,609 ptVALIANT TrialSCD – 7%,MI后患者的猝死率,Solomon: NEJM, 2005,CP1196896-3,,MI后的平均時(shí)間?入組時(shí)間,5 days,,

7、心肌梗死后的時(shí)間,心臟停搏或猝死率 (%/mo),,,,,,,,,14,609 ptVALIANT TrialSCD – 7%,LVD和CHF心肌梗死后患者的猝死率,Solomon: NEJM, 2005,CP1196896-3,,MI后的平均時(shí)間?入組時(shí)間,5 days,,心肌梗死后的時(shí)間,心臟停搏和猝死率 (%/mo),,LVEF ?30% (n=3,852)LVEF 31-40% (n=4,898)LVEF >40

8、% (n=2,406),,,,DINAMIT Trial – 從ICD中不能獲益全因死亡率,CP1182269-1,,累計(jì)風(fēng)險(xiǎn),P=0.66,隨機(jī)化的時(shí)間,ICD,Control,,,近期MI (6-40 days)EF ?0.35? HRV,674 pt,Hohnloser: NEJM, 2005,MI后的LV 功能下降的死亡原因,CP1200978-1,OPTIMAAL TrialLosartan/CaptoprilMI

9、 <10 天CHF/LV功能失調(diào),180 pt – 尸檢報(bào)告,Orn: AJM, 2005,,累計(jì)死亡率 (%),CABG后預(yù)防性應(yīng)用ICDCABG – PATCH Trial,CP1157419-4,,900 ptCABGsurgery年齡 <80 yrEF <0.36 + 異常的平均電信號(hào)心電圖,月,Bigger: NEJM, 1997,死亡概率,對(duì)照組,除顫組,,,CHF 患者中未進(jìn)行SCD-

10、CASS注冊(cè)的比例,Holmes: Circ, 1986,未猝死患者 (%),CP1176240-8,MI后-入選研究的平均時(shí)間,,39,MUSTT,81,MADIT-II,<1,DINAMIT,Bunxton: NEJM, 2005,在MUSTT 試驗(yàn)中近期MI的時(shí)間,,,EP-guided RxNo AA drug Rx,,,月,?1,可誘發(fā)、持續(xù)性 VTEF ?0.4CAD/Prior MINSVT,1-3,3-

11、6,6-12,12-36,>36,704 pt,MUSTT隨機(jī)對(duì)照試驗(yàn)患者心律失常性死亡或心臟停搏,,,發(fā)生事件的病人數(shù)(no.),EP-guided RxNo AA drug Rx,,,61224364860,P=0.043Hazard ratio = 0.73 (0.53-0.99),月,,多中心的自動(dòng)除顫器植入試驗(yàn)（ MADIT I ）,累計(jì)生存率,P=0.009,隨機(jī)對(duì)照后觀察的時(shí)間,ICD,Control

12、,,NYHA I, II, IIIPrior MIEF ?0.35Inducible VT,196 pt,,MI后ICD獲益的時(shí)間依賴性,MADIT II substudyLVEF ?30%Prior MI ?1 mo(mean 81 mo),累計(jì)存活率校正 BL 不同,存活率的分布曲線,Wilber: Circ, 2004,（年）,,存活率分布曲線,,ICD,常規(guī)治療,ICD,常規(guī)治療,HR=0.97 (0.51, 1

13、.81),HR=0.55 (0.39, 0.78),P=0.92,P=0.001,Remote MI (?18 mo),近期心梗 (<18 mo),,,,,CP1215754-3,MI后猝死的機(jī)制可能的機(jī)制,近期心梗后無ICD的獲益假說,早期死亡,晚期死亡,再發(fā)心梗CHF,心律失常性猝死,心肌重塑代償性 CHF,室性心律失常,從ICD中 獲益較少,從ICD中獲益,,,,,,,CP1220421-1,Bunch TJ, G

14、ersh BJ. Circulation 2007,心衰、缺血性心臟病的一級(jí)預(yù)防,,多中心自動(dòng)除顫器植入的試驗(yàn)(MADIT II),累計(jì)發(fā)生率,P=0.007,年,ICD,對(duì)照組,,Prior MI (>1 mo)EF ?0.30NYHA I, II, III,1232 pt,,,QRS時(shí)間的意義,,,,,,,QRS,<120,120-150,>150,ICD 獲益,ICD無獲益,死亡的相對(duì)危險(xiǎn)性,,,總體死亡率

15、,猝死率,心衰試驗(yàn)中的猝死率 (SCD-HeFT),累計(jì)危險(xiǎn)度,Bardy: NEJM, 2005,年,Placebo,ICD,P=0.05,P=0.06,,,,,EF ?0.35NYHA II, III52% ischemic DCM,2521 pt,,,Amio,Amio,Placebo,ICD,累計(jì)危險(xiǎn)度,心衰、非缺血性心臟病一級(jí)預(yù)防,,,總體死亡率,猝死率,非缺血性心肌病中除顫器治療的評(píng)價(jià),死亡率,Kadish: NEJ

16、M, 2004,年,死亡率,ICD,Conventional,ICD,Conventional,P=0.08,P=0.006,,,,,EF ?0.36NYHA I, II, IIIAmbient arrhythmias,458 pt,亞組分析,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,性別女性男性年齡65 yrLVEF20%QRS120 msNYHAIIIIIIAFNo

17、YesAll,ICD 獲益,ICD 未獲益,死亡相對(duì)危險(xiǎn)性,,,ICD治療的獲益時(shí)間(DEFINITE Trial),ICD,對(duì)照組,,ICD,對(duì)照組,,,,P=0.049,P=0.483,存活率 （天）,NIDCM < 3 mos,NIDCM > 3 mos,Kadish: JACC, 2005,,,總體死亡率,猝死率,心衰試驗(yàn)中的猝死率(SCD-HeFT),Cumulative Risk,Bardy: NEJM,

18、 2005,年,Placebo,ICD,P=0.05,P=0.06,,,,,EF ?0.35NYHA II, III52% ischemic DCM,2521 pt,,,Amio,Amio,Placebo,ICD,Cumulative Risk,,糖尿病,CABG Patch,,,ICD一級(jí)預(yù)防的作用,Sanders: NEJM, 2005,CP1234274-3,Buxton: Circ, 2002,1,791 ptMUST

19、T trialEF ?40%Documented CAD,EF比值與死亡模式的關(guān)系,CP1230337-1,,LVEF的分布,CP1222765-3,正常EF比值的心臟性猝死,Stecker: AHA, 2006,Multnomah County, Oregon202 pt入院存活率,,正常,EF.36-.54,<36%,42%,38%,20%,AMI – 42%AMI/有缺血性癥狀 CAD – 61%無冠脈缺血證

20、據(jù)– 22%,,除顫器械的選擇及程控,雙腔和VVI植入性除顫器的試驗(yàn) (DAVID),506 pts, EF<40% ICD適應(yīng)證VFVT 有暈厥VT 無暈厥，但 EF<40%, and SBP < 80 mmHg, 胸痛, CHF, 近似暈厥誘發(fā)的VT/VF at EP 研究中DDDR-70 (60% paced) vs VVI-40 (1% paced),Wilkoff BL, Cook JR, et a

21、l. JAMA 2002; 288:3115,N at riskDDDR 250 159 76 21VVI 256 158 90 25,P=0.03,隨訪時(shí)間,

22、.4,.3,.2,.1,.0,0,6,12,18,DDDR (70),VVI (40),,,累計(jì)概率,,,,,,,,,,,,,,Wilkoff BL, Cook JR, et al. JAMA 2002; 288:3115,雙腔和VVI植入性除顫器的試驗(yàn),COMPANION死亡率或入院率,,,,,,,,,,,,,,,,,,,,0,20,40,60,80,100,0,120,240,360,480,600,720,840,960,10

23、80,無事件存活 (%),隨機(jī)后觀察時(shí)間,起搏器-除顫器(390 events, P=0.010),起搏器 (414 events, P=0.014),藥物治療 (216 events),Bristow MR, Saxon LA, et al. NEJM 2004; 350:2140,COMPANION全因死亡率,,,,,,,,,,,,,,,,,,,50,60,70,80,90,100,0,120,240,360,480,600,

24、720,840,960,1080,無事件存活 (%),隨機(jī)后觀察時(shí)間（天）,起搏器-除顫器 (105 events, P=0.003),藥物治療 (77 events),起搏器(131 events, P=0.059),,Bristow MR, Saxon LA, et al. NEJM 2004; 350:2140,,,,,,,,,,,,,,,,,,,,,QRS≥120,QRS<120,QRS≥120,QRS<120,

25、QRS≥120,QRS<120,QRS≥120,QRS<120,Peak O2 Consumption,NYHA Class,QOL Scores,6 Minute Walk,p=0.24,p=0.02,p=0.63,p=0.24,p=0.31,p=0.76,p=0.04,p=0.01,基線水平變化 (%),基線水平變化 (%),基線水平變化 (%),基線水平變 (%),Median,Median,RethinQ 研究,17

26、2 個(gè)病人，標(biāo)準(zhǔn)ICD適應(yīng)證、 QRS <130 ms、收縮不同步,Beshai NEJM 2007,CRT對(duì)無癥狀性的左心室功能障礙的影響,NYHA 1-2QRS>120 msLVEF<0.4,,CRT off,CRT on,,,HR 惡化,HF 改善/未變化,610 pt,Linde C. ACC Late Breaking Clinical Trials, 2008,植入CRT12個(gè)月時(shí)對(duì)無癥狀性的左心室

27、功能障礙的影響,,CRT off,CRT on,,,,? LVESV,? LVEDV,? EF,-1.3,1.4,0.6,-18.4,-20.5,3.8,All <0.0001,Linde C. ACC Late Breaking Clinical Trials, 2008,植入CRT12個(gè)月時(shí)對(duì)無癥狀性的左心室功能障礙的影響,,CRT off,CRT on,8.6%,11.9%,Gold MR. HRS Late Break

28、ing Clinical Trials, 2008,室顫/心動(dòng)過速,無癥狀性的左心室收縮功能異常的流行病學(xué),Wang TJ. Ann Intern Med 2003,,Strong Heart,HyperGen,Davies,MONICA EF<35,MONICA EF<30,2.9,2.1,4.0,3.4,1.8,0.9,7.7,5.9,2.9,1.4,,,Ejection Fraction <0.4,Ejecti

29、on Fraction <0.4 (no CHF),植入ICD患者的心房顫動(dòng),植入ICD后通過病史及心房顫動(dòng)短期發(fā)病率判斷預(yù)后,,,,,,No AF, No History,AF, No History,No AF, AF History,AF, AF history,Percent (%),Death,HF 入院率,Death/HF入院率,ICD休克,P=0.04,P=0.67,P=0.83,P=0.22,P=0.68,P=0.

30、32,P=0.66,P=0.74,Bunch TJ, Heart Rhythm (in press),N=1,530,MI后心房顫動(dòng)及心臟性猝死跟蹤注冊(cè)研究,,SC死亡危險(xiǎn)比,MI后的時(shí)間（月）,Pederson: Eur Heart J, 2005,5983 ptMI with CHFRandomized to Trandolapril vs placebo,,,AF/AFL,No AF/AFL,P<0.009,ICD的

31、臨床試驗(yàn)和臨床標(biāo)記物,需要考慮的因素及其限制性,EF測(cè)量的準(zhǔn)確性EF界值與可能的致死性室速的關(guān)系,Bunch TJ, Gersh BJ. Circulation 2007,CP1255114-20,ACC/AHA/HRS 2008 心律失常的器械治療指南,ACC/AHA/ESC: Circulation 2008,ICD,觀察,目標(biāo)性Tx的觀察,,,缺血性心臟疾病EF<35,,,,,VF/VT,近期心梗及再血管和治療,遺

32、傳性的離子通道病, HCM, ARVD,最優(yōu)化的醫(yī)療措施,,,是否有可逆轉(zhuǎn)的原因,,,否,是,,暈厥的高危特點(diǎn),,觀察40天TX危險(xiǎn)因子,,ICD,EF<35VT,,,不,是,,心臟性猝死,是,否,,是,不,,,觀察,是,,NYHA分級(jí),,,,,是,,否,ICD,否,暈厥的高危特點(diǎn),,,否,,,評(píng)估EF藥物的獲益,,QRS>120,,NYHA Class II-III,,CRT,Thank YouXie X