輕心衰患者的crt應(yīng)用梁兆光

輕心衰患者的crt應(yīng)用梁兆光第1頁(yè)/共37頁(yè)2004之前的臨床研究證實(shí)CRT改善NYHAIII/非臥床IV級(jí)，LV功能不全和寬QRS患者的心衰癥狀改善生活質(zhì)量增加活動(dòng)能力逆轉(zhuǎn)LV重構(gòu)-LVsize,LVEF減少二尖瓣返流第2頁(yè)/共37頁(yè)CardiacResynchronizationTherapy(CRT)ReducesHospitalizations,andCRTwithImplantableDefibrillator(CRT-D)ReducesMortalityinChronicHeartFailure:

TheCOMPANIONTrial

BristowMR,(Co-Ch)FeldmanAM,(Co-Ch)SaxonLA,DeMarcoT,KassD,BoehmerJ,MannD,SinghS,CarsonP,KruegerS,McGrewF,BotteronG,WagonerL,fortheCOMPANIONInvestigatorsBristowMR

,etal.NEnglJMed.2004May20;350(21):2140-50

.第3頁(yè)/共37頁(yè)COMPANION研究設(shè)計(jì)一級(jí)終點(diǎn):全因死亡或全因住院的復(fù)合終點(diǎn)主要入選標(biāo)準(zhǔn)NYHAClass:NYHAIII/IVLVEF:≤35%QRSDuration:≥120msec研究中心:122UScenters基礎(chǔ)評(píng)估隨機(jī)1:2:2CRT-P(N=617)CRT-D(N=595)平均隨訪(fǎng)12個(gè)月BristowMR

,etal.NEnglJMed.2004May20;350(21):2140-50

.OPT(N=308)第4頁(yè)/共37頁(yè)COMPANION顯示在NYHAIII/IV的患者中CRT-P和CRT-D分別降低19%和20%的

全因死亡和全因住院的復(fù)合終點(diǎn)第5頁(yè)/共37頁(yè)COMPANION顯示在NYHAIII/IV的患者中CRT-P和CRT-D分別降低24%和36%的

全因死亡率第6頁(yè)/共37頁(yè)TheCARE-HFStudy

CArdiacREsynchronisationinHeartFailureJohnGFCleland-Kingston-upon-Hull.UKJean-ClaudeDaubert–Rennes.FranceErlandErdmann–Cologne.GermanyNickFreemantle–Birmingham.UKDanielGras–Nantes.FranceLukasKappenberger–Lausanne.SwitzerlandWernerKlein–Graz.AustriaLuigiTavazzi–Pavia.ItalyonbehalfoftheCARE-HFStudyInvestigators

ClelandJGF

NEngJMed2005;352:1539-49第7頁(yè)/共37頁(yè)CARE-HF研究設(shè)計(jì)一級(jí)終點(diǎn):全因死亡率或主要心血管事件計(jì)劃外住院率主要入選標(biāo)準(zhǔn)NYHAClass:NYHAIII/IVLVEF:≤35%QRSDuration:≥120msec研究中心:82Europeancenters基礎(chǔ)評(píng)估隨機(jī)1:1CRT-P(N=409)平均隨訪(fǎng)29個(gè)月OPT(N=404)

ClelandJGF

NEngJMed2005;352:1539-49第8頁(yè)/共37頁(yè)348118232292404MedicalTherapy768166273323409CRTNumberatrisk0500100015000.000.250.500.751.00HR0.63(95%CI0.51to0.77)Event-freeSurvivalDaysP<.0001CRT藥物治療CARE-HF顯示在NYHAIII/IV的患者中CRT-P降低37%的

全因死亡和心血管病因住院的復(fù)合終點(diǎn)第9頁(yè)/共37頁(yè)CARE-HF研究顯示在NYHAIII/IV患者中CRT-P降低40%的全因死亡率ClelandJGF.EurHeartJ.2006Aug;27(16):1928-324093833583382098540437233129817863CRTMedicaltherapyNumberatrisk96Time(days)Medical

TherapyMeanFollow-up36.4months(range26.1to52.6)CRTDeaths=101(24.7%)MedicalTherapyDeaths=154(38.1%)CRT040016000.000.250.508001200HazardRatio0.60(95%CI0.47to0.77;P<0.0001)40%reductionwithCRTMortality第10頁(yè)/共37頁(yè)2006年中國(guó)CRT指南/2007ESC/2008ACC/AHA/HRS指南更新Dicksteinetal.EurHeartJ.2008.DOI:10.1093/eurheartj/ehn309CRTindicatedHFNYHAIII/IV?

Yes

NoLevelIAQRS>120ms?

Yes

No

EF<35%?

Yes

NoLevelIACRT-Dindicated預(yù)計(jì)生存

>1年?所有患者都為藥物優(yōu)化第11頁(yè)/共37頁(yè)CRT治療輕度心衰的臨床研究第12頁(yè)/共37頁(yè)REsynchronizationreVErsesRemodelinginSystolicleftvEntriculardysfunction:ResultsoftheREVERSETrialCeciliaLinde,Stockholm,SwedenWilliamT.Abraham,Columbus,U.SMichaelR.Gold,Charleston,U.S.Jean-ClaudeDaubert,Rennes,France

OnBehalfoftheREVERSEInvestigatorsandCoordinators第13頁(yè)/共37頁(yè)REVERSE研究設(shè)計(jì)一級(jí)終點(diǎn):心衰的臨床綜合反應(yīng)惡化%主要的二級(jí)終點(diǎn):左室容量指數(shù)(LVESVi)主要入選標(biāo)準(zhǔn)NYHAClass:NYHAII或先前有癥狀的NYHAILVEF:≤40%QRSDuration:≥120msec研究中心:73centres:US(37);Canada(1);Europe(35)資助:Medtronic基線(xiàn)評(píng)估隨機(jī)1:2雙盲CRTOff(n=191)CRTOn(N=419)LindeC,etal.JAmCollCardiol.2008;52:1834-43.DaubertC,etal.JAmCollCardiol2009;54(20):1837-46.CRTOff(n=82)CRTOn(N=180)12Months24Months(Europe)第14頁(yè)/共37頁(yè)REVERSE一級(jí)終點(diǎn):臨床綜合反應(yīng)(惡化%)1LindeC,etal.JAmCollCardiol.2008;52:1834-43.2DaubertC,etal.JAmCollCardiol2009;54(20):1837-46.24Months2P=0.01P=0.0006P=0.1012Months1P=0.004第15頁(yè)/共37頁(yè)REVERSE主要二級(jí)終點(diǎn):LVESVi平均變化12Months1P<0.000124Months2P<0.00011LindeC,etal.JAmCollCardiol.2008;52:1834-43.2DaubertC,etal.JAmCollCardiol2009;54(20):1837-46.第16頁(yè)/共37頁(yè)NumberatRisk

CRTOFF8279767039

CRTON1801761731687762%reductionwithCRTREVERSE24-months:第一個(gè)臨床研究顯示在NYHAII患者中降低第一次HF住院或死亡62%…第17頁(yè)/共37頁(yè)MADITCRT研究設(shè)計(jì)一級(jí)終點(diǎn):全因死亡,或非致命的心衰事件主要入選標(biāo)準(zhǔn)NYHAClass:任何病因的NYHAII;心梗后NYHAILVEF:≤30%QRSDuration:≥130msec研究中心:110centres:US(88);Europe(20);Canada(2)資助t:BostonScientific基線(xiàn)評(píng)估隨機(jī)2:3非盲ICDOnly(N=731)CRT-D(N=1089)平均隨訪(fǎng)29個(gè)月MossAJ,etal.NEnglJMed.2009;361(14):1329-38.第18頁(yè)/共37頁(yè)MADIT-CRT顯示在NYANI/II患者中CRT-D減少34%的全因死亡或心衰事件風(fēng)險(xiǎn)34%reductionwithCRTMADITCRT證實(shí)了REVERSE:CRT減少死亡或心衰事件第19頁(yè)/共37頁(yè)MADITCRT超聲LV容積和EF一年的平均變化P<0.001P<0.001P<0.001MossAJ,etal.NEnglJMed.2009;361(14):1329-38.第20頁(yè)/共37頁(yè)Resynchronization–Defibrillationfor

AmbulatoryHeartFailureTrial

RAFTAnthonyS.L.Tang,M.D.,GeorgeA.Wells,Ph.D.,MarioTalajic,M.D.,MalcolmO.Arnold,M.D.,RobertSheldon,M.D.,StuartConnolly,M.D.,StefanH.Hohnloser,M.D.,GrahamNichol,M.D.,DavidH.Birnie,M.D.,JohnL.Sapp,M.D.,RaymondYee,M.D.,JeffreyS.Healey,M.D.,andJeanL.Rouleau,M.D.,TangAS,WellsGA,TalajicM,etal.Cardiac-resynchronizationtherapyformild-to-moderateheartfailure.EnglJMed.2010Dec16;363(25):2385-95第21頁(yè)/共37頁(yè)RAFT研究設(shè)計(jì)一級(jí)終點(diǎn):全因死亡,或心衰住院主要入選標(biāo)準(zhǔn)NYHAClass:NYHAII/IIILVEF:≤30%QRSDuration:≥120msec;或起搏≥200msec研究中心:34centres:Canada(24);Europe(8);Australia(2)資助:CanadianInstitutesofHealthResearch,Medtronic基線(xiàn)評(píng)估隨機(jī)1:1雙盲ICDOnly(N=904)CRT-D(N=894)平均隨訪(fǎng)40個(gè)月第22頁(yè)/共37頁(yè)RAFT顯示在NYHAII/III患者中CRT-D降低25%全因死亡或心衰住院復(fù)合終點(diǎn)25%reductionwithCRT第23頁(yè)/共37頁(yè)25%reductionwithCRTRAFT顯示在NYHAII/III患者中CRT-D降低25%全因死亡率第24頁(yè)/共37頁(yè)主要入選標(biāo)準(zhǔn)&研究設(shè)計(jì):REVERSEMADITCRTRAFTNYHA心功能分級(jí)I,III(post-MIonly),IIII,IIILVEF≤40%≤30%≤30%QRSduration≥120ms≥130ms≥120msAFNoNoPermitted患者數(shù)610(503Cl.II)1820(1555Cl.II)1798(1438Cl.II)一級(jí)終點(diǎn)臨床復(fù)合反應(yīng)惡化%全因死亡或HF事件全因死亡或HF住院結(jié)果臨床復(fù)合反應(yīng)@12months,21%CRTOFF惡化vs.16%CRTON,p=0.10.@24months(Europeonly),34%CRTOFF惡化vs.19%CRTON,P=0.007.無(wú)報(bào)告無(wú)報(bào)告(死亡率和HF事件*復(fù)合終點(diǎn)降低95%confidenceinterval)12months:沒(méi)有報(bào)告24months:62%,p=0.003所有患者:34%(16%,48%)NYHAClassII:沒(méi)有報(bào)告所有患者:25%(13%,36%)NYHAClassII:27%(12%,39%)CRT/D降低HF事件*(95%CI)12months:53%,p=0.0324months:61%,p=0.01所有患者:41%(26%,53%)NYHAClassII:無(wú)報(bào)告所有患者:32%(17%,44%)NYHAClassII:30%(11%,45%)CRT/D降低全因死亡率(95%CI)12months:無(wú)差異,P=0.6324months:無(wú)差異,p=0.09所有患者:無(wú)差異,P=0.99Allpatients:25%(9%,38%),p=0.003NYHAClassII:29%(9%,44%),p=0.006CRT-D/P,ICDproductMedtronicBostonScientificMedtronic第25頁(yè)/共37頁(yè)NumberatRisk CRTOFF8279767039

CRTON1801761731687762%reductionwithCRTREVERSE(24-m)顯示:在NYHAII患者中降低第一次HF住院或死亡62%Daubertetal.JAmCollCardiol2009;Vol54,No20CRT在NYHAII中的臨床效果與NYHAIII-IV一樣的MADITCRT證實(shí)REVERSE：CRT降低心衰事件或死亡RAFT進(jìn)一步證實(shí)：CRT降級(jí)心衰死亡或住院25%reductionwithCRTCARE-HF:CRT降低死亡或心血管事件住院率第26頁(yè)/共37頁(yè)CRT在NYHAII中的臨床效果與NYHAIII-IV一樣的

…有關(guān)心臟重構(gòu)的作用LVESV0ml-27mlp<0.001ChangefrombaselineinmlLVEFChangefrombaselinein%unitsp<0.0012%7%CRT-ONCRT-OFFCRT-ONCRT-OFFDaubertetal.JAmCollCardiol2009;Vol54,No20第27頁(yè)/共37頁(yè)REVERSE和MADIT-CRT影響了

2009中國(guó)CRT指南/2010ESCCRT指南Dicksteinetal.EurHeartJ.2008.DOI:10.1093/eurheartj/ehn309CRTindicatedHFNYHAIII/IV? Yes NoQRS>120ms? Yes No

EF<35%? Yes NoCRT-Dindicated所有患者都為藥物優(yōu)化HFNYHAII?

Yes NoQRS>150ms? Yes No

EF<35%? Yes NoHFNYHAII?

Yes NoQRS>120ms? Yes No

EF<35%? Yes No2010ESC2009中國(guó)ILevelAIIA第28頁(yè)/共37頁(yè)輕度心衰患者QRS波越寬獲益越大在REVERSE,MADITCRT和RAFT三個(gè)臨床中，發(fā)現(xiàn)QRS波越寬的患者，特別是≥150ms，從CRT中獲益越多，這意味QRS波的寬度對(duì)于選擇對(duì)CRT有反應(yīng)的患者是一個(gè)非常重要的指標(biāo)REVERSE(12m)RAFTMADITCRT第29頁(yè)/共37頁(yè)三個(gè)臨床研究共同證實(shí)CRT降低NYHAII級(jí)患者的死亡率或心衰事件，尤其是CRT-D缺血和非缺血心衰患者同樣受益患者QRS波越寬獲益越大第30頁(yè)/共37頁(yè)Medtronic引領(lǐng)心衰臨床研究第31頁(yè)/共37頁(yè)10075502500123456YearsDevicelongevitypercentp<0.0001IntermedicBostonScientificMedtronicStJude1007550250

0244872 96MonthsMedtronicPercentofdevicesevent-freep<0.0001BiotronikELABostonScientificStJudeKnopfetal2009.PACE32:1276–1285Schereretal2009.HeartRhythminpress.DOI:10.1016/j.hrthm.2009.09.0