缺血性和非缺血性心肌病心源性猝死的預(yù)防

缺血性和非缺血性心肌病心源性猝死的預(yù)防ConflictsofInterestBostonScientific:speakershonorarium0125102030

發(fā)生率(%/年)0100200300(x1000)事件發(fā)生率（/年）

STDS

ICD試驗中研究對象的對比Myerberg:Circ,1998既往有心臟事件多風(fēng)險亞組一般成年人群心梗后高風(fēng)險亞組MADITMUSTTCP1185382-11VF/VT所致心臟驟停的幸存者AVIDCASHCIDSEF<35%或心衰MADIT2SCD-HeFT適于ICD預(yù)防心源性猝死的人群比例？

OREGONSUD研究CP1201806-4SteckerandChugh:42:446AJACC,2005(Abstract)%生存率(%)年

年齡-性別-疾病匹配的對照組(p=0.68)治療組U.S.普通人群對照組(p=0.02)遠(yuǎn)期生存率

BunchTJ,WhiteRD,NEJM,2003與普通美國人群相比P值0.270.120.730.140.190.070.650.010.330.190255075100精神健康

軀體健康生命力

社會功能

生理職能情感職能

軀體功能

心理健康指數(shù)

總體健康感

疼痛指數(shù)

*預(yù)期更差遠(yuǎn)期生活質(zhì)量BunchTJ,WhiteRD,NEJM,2003AVID試驗中患者生存率（未校正）生存比例高風(fēng)險患者 1,016 644 333 104生存率(%)除顫器組 89.3 81.6 75.4抗心律失常藥物組 82.3 74.7 64.1年NEJM337:1576,1997P<0.02除顫器組抗心律失常藥物組CP971778-41累積風(fēng)險胺碘酮組ICD組高風(fēng)險患者胺碘酮組 331 304 285 240 204 173 152 123 89ICD組 328 305 288 245 215 179 153 134 101D 3 1 3 5 11 6 1 11 12隨機分組后時間（月）

1p=0.0722p=0.14CIDS

研究生存分析：全因死亡CP971778-18MADITI試驗累積生存率P=0.009隨機分組后時間（年）ICD組對照組心功能分級I,II,III既往MIEF0.35可誘導(dǎo)VT196例病人心肌梗死患者植入ICD獲益的時間依賴性MADITII亞組LVEF30%既往MI1個月

(平均81個月)累積生存率（校正后）生存分布函數(shù)Wilber:Circ,2004年生存分布函數(shù)ICD組普通治療組ICD組普通治療組HR=0.97(0.51,1.81)HR=0.55(0.39,0.78)P=0.92P=0.001

MI18個月MI<18個月

CP1215754-314,609例VALIANT試驗心源性猝死–7%心肌梗死后心源性猝死Solomon:NEJM,2005CP1196896-3心梗后注冊平均時間5天心肌梗死后時間（月）心源性猝死或心臟驟停并成功復(fù)蘇的發(fā)生率12345612243648DINAMIT試驗–從ICD中獲益較少

全因死亡CP1182269-1全因死亡的累積風(fēng)險P=0.66隨機分組后時間（月）ICD組對照組新近MI(6-40天)EF0.35HRV674例Hohnloser:NEJM,2005心肌梗死合并左室功能不全者死亡的原因CP1200978-1OPTIMAAL試驗氯沙坦/開博通MI<10天慢性心衰/左室心功能不全180例–尸檢報告心源性猝死

14%MI

51%其它

29%死亡原因–尸檢Orn:AJM,2005總死亡率猝死SCD-HeFT研究累積風(fēng)險Bardy:NEJM,2005年P(guān)laceboICDP=0.05P=0.06EF0.35心功能分級II,III52%擴心病并心肌缺血2521例AmioAmioPlaceboICD累積風(fēng)險總死亡猝死DEFINITE試驗

（抗心律失常藥治療非缺血性心肌病的療效評價）生存率Kadish:NEJM,2004年生存率ICD組藥物治療組ICD組藥物治療組P=0.08P=0.006EF0.36心功能分級I,II,IIIAmbientarrhythmias458例DEFINITE試驗ICD組對照組ICD組對照組P=0.049P=0.483生存(天)NIDCM<3個月NIDCM>3個月Kadish:JACC,2005常規(guī)治療的全因死亡率(%/年)DEFINITESCD-HeFTMADITIIMUSTTMADITICOMPANIONICD與常規(guī)治療比較死亡危險的風(fēng)險比DINAMITCABGPatchICD用于一級預(yù)防的效果Sanders:NEJM,2005CP1234274-3Buxton:Circ,20021,791例MUSTT試驗EF40%確診的CADEF與死亡模型的相關(guān)性CP1230337-1射血分?jǐn)?shù)（EF）事件發(fā)生率EF與全因死亡、或心律失常死亡/心臟驟停的關(guān)系死亡心律失常死亡/心臟驟停COMPANION

全因死亡506070809010001202403604806007208409601080無事件生存率(%)隨機分組后時間（天）起搏器-除顫器(105個事件,P=0.003)藥物治療

(77個事件)起搏器

(131個事件,P=0.059)BristowMR,SaxonLA,etal.NEJM2004;350:2140CRT對無癥狀左室功能不全的影響

（1年結(jié)果）非CRT組CRT組

左室收縮末容積

左室舒張末容積EF-1.3-1.40.6-18.4-20.53.8P均<0.0001LindeC.ACCLateBreakingClinicalTrials,2008MADIT-CRT研究MossAetal.NEnglJMed2009;10.1056/NEJMoa0906431僅ICD生存率年（隨機分組后）生存率無心衰事件僅ICDQRS≥120QRS<120QRS≥120QRS<120QRS≥120QRS<120QRS≥120QRS<120氧耗峰值心功能分級生活質(zhì)量分值6分鐘步行p=0.24p=0.02p=0.63p=0.24p=0.31p=0.76p=0.04p=0.01基線變化范圍(%)基線變化范圍(%)基線變化范圍(%)基線變化范圍(%)中位數(shù)中位數(shù)RethinQ研究172例病人,標(biāo)準(zhǔn)的ICD適應(yīng)證,QRS<130ms,心室非同步收縮BeshaiNEJM2007左室射血分?jǐn)?shù)分布情況CP1222765-3EF正常的心臟驟停

Stecker:AHA,2006MultnomahCounty,Oregon202例病人住院生存率正常EF.36-.54<36%42%38%20%AMI–42%AMI或有缺血癥狀的阻塞性冠心病–61%未經(jīng)證實的冠脈缺血–22%減少危險因子有效治療高脂血癥有效控制高血壓

有益于心臟健康的飲食

有規(guī)律的體育鍛煉

戒煙

適量飲酒

有效控制糖尿病Yaggi,H.etal.NEnglJMed2005;353:2034-2041合并阻塞性睡眠呼吸暫停（OSA）的猝死生存率年OSA組對照組P=0.0301020304050心源性猝死的晝夜規(guī)律心源性猝死的比例(%)0:00-5:59時間（24小時）

6:00-11:5912:00-17:5918:00-23:5921%41%26%12%無OSA(n=34)16%30%29%25%普通人群P<0.001P=0.01P<0.001P=0.02P=0.0446%20%9%24%OSA(n=78)GamiAS,HowardDE,OlsonEJ,SomersVK.NEJM,2005無癥狀左室收縮功能不全的流行病學(xué)

WangTJ.AnnInternMed2003StrongHeartHyperGenDaviesMONICAEF<35MONICAEF<302.92.14.03.41.80.97.75.92.91.4EF<0.4EF<0.4(無CHF)無癥狀左室收縮功能不全的疾病分布情況WangTJ.AnnInternMed2003StrongHeart(n=444)SOLVDPrevention(n=2117)Davies(n=72)MONICA(n=43)糖尿病心肌梗死高血壓193373152646157937魚肉或魚油與猝死風(fēng)險每周魚肉的攝入量02460.51.01.52.0相關(guān)風(fēng)險度相關(guān)風(fēng)險度N-3脂肪酸攝入量,g/月02460.51.01.52.0810Albert,CM,Hennekens,CH,O'Donnell,CJ,etal.JAMA1998;279:23.

根本在于基因44例圍產(chǎn)期心肌病12NSVT/VT4q25-q27p=10-4to10-54q25-q27–編碼帶與長QT及鈉通道有關(guān)LimT,HorneB,BunchTJ家族史中有心臟驟停者，不論是否合并心肌梗死，其心臟驟停的風(fēng)險增加倍心律失常與先天條件

CP1052359-2長QT間期綜合癥Brugada綜合癥多形性室速短QT間期綜合癥家族性房顫病態(tài)竇房結(jié)綜合癥肥厚性心肌病致心律失常性右心室疾病擴張性心肌病結(jié)構(gòu)性疾病離子通道疾病ICD適應(yīng)癥I類（二級預(yù)防）因室顫或血流動力學(xué)不穩(wěn)定的持續(xù)性室速所至猝死成功復(fù)蘇后，無可糾正的可逆性病因者（證據(jù)級別：A）。

CP1313975-9Epsteinetal:JACC51(21):2085,2008ICD適應(yīng)癥IIa類

服用b-受體阻滯劑期間發(fā)生暈厥和（或）室速的長QT間期綜合癥患者（證據(jù)級別：B）。有暈厥史或室速而無心臟驟停的Brugada綜合癥患者（證據(jù)級別：C）。肥厚性心肌病且有1個心源性猝死的危險因素者（證據(jù)級別：C）。CP1313975-13ModifiedfromEpsteinetal:JACC51(21):2085,2008ICD適應(yīng)癥IIb類長QT間期綜合癥，且有心源性猝死的危險因素者（證據(jù)級別：C）。CP1313975-15ModifiedfromEpsteinetal:JACC51(21):2085,2008CP1255114-20ACC/AHA/HRS2008心臟節(jié)律異常裝置治療指南ACC/AHA/ESC:Circulation2008ICD觀察定向Tx觀察缺血性心臟病EF<35VF/VT

近期心肌梗死或血運重建遺傳性離子通道疾病,HCM,ARVD理想的藥物治療可逆的原因?否是暈厥高危特征觀察40天TX危險因子ICDEF<35VT否是心臟驟停是否是否觀察是紐約心功能分級的作用?是否ICD否暈厥高危特征否再評估EF藥物治療能否獲益?QRS>120紐約心功能分級II-IIICRTICDThankYouXieXieCongenitalLQTSTherapyB-blockertherapy

Firstlinetherapy Asymptomaticptswithdefinitivedx Contraindicated:LQT3? ICD Failed/intolerant/non-compliantofmedicalRx IncreasedriskofSCD(1o&2oprevention) Leftcardiacsympatheticdenervation/PM Long-termoutcomesinsmalltrialsarepromisingLeftstyle/activitymodification

Required,impactspatientQOL(?Roleof denervation)Gene-guidedtherapy

EvolvingapproachDEBUTStudyProfileBrugadaSyndromeNademanee:Circ,2003Patientsscreenedn=155Activepatientsn=66Activepatientsn=37Activepatientsn=29Activepatientsn=37Deathn=0Activepatientsn=25Deathn=4Treatedbydevicen=7

64 ProbableSUDSeither

noninducibleorunclear

marker 5 Brainanoxic

encephalopathy 2 PreferICDtreatment 1 RandomizedtoICDbut

refused 10 Refusedenrollment 6 Presenceofheartdisease 1 EnteredafterDSMB,

stoppedthetrialNotrandomizedn=89ICD-blockersCP1205334-1CumulativeproportionofsurvivalTimetodeath(months)P=0.02ICD-blockersStratificationofRiskandPreventionofSuddenDeathinHypertrophicCardiomyopathyCP1237791-8SpiritoandAutore:BMJ332:1251,2006SecondarypreventionImplantable

cardioverter

defibrillatorPrimaryprophylacticpreventionAssessoverallpatientriskprofileAbortedcardiacarrestSustainedVTFHxofprematuresuddendeathExtremeLVH(30mm)inyoungptUnexplainedsyncopeinyoungptNSVTinptaged30yrAbnormalBPresponse

duringexerciseMildLVH(<20mm)andno

riskfactorsHighriskModerateriskLowriskT.JaredBunchMDSuddenCardiacDeathPreventioninIschemicandNonischemicCardiomyopathyIntermountainHeartRhythmSpecialists,IntermountainMedicalCenterConflictsofInterestBostonScientific:speakershonorarium0125102030Incidence(%/yr)0100200300(x1000)Events(no./yr)STDSPopulationImpactofEmerging

ICDTrialsMyerberg:Circ,1998Anyprevious

coronaryeventMulti-risk

subgroupGeneraladult

populationHigh-riskpost-MI

subgroupsMADITMUSTTCP1185382-11Cardiacarrest

VF/VTsurvivorsAVIDCASHCIDSEF<35%orheart

failureMADIT2SCD-HeFTWhatProportionWouldHave

QualifiedforPreventionwithICD?

OREGONSUDStudyCP1201806-4SteckerandChugh:42:446AJACC,2005(Abstract)%Survival(%)YearsExpectedAge-Gender-andDisease-matchedcontrols(p=0.68)ObservedExpectedU.S.generalcontrols(p=0.02)Long-termsurvivalBunchTJ,WhiteRD,NEJM,2003ComparisonwithgeneralU.S.populationp-value0.270.120.730.140.190.070.650.010.330.190255075100PhysicalcomponentMentalcomponentVitalitySocialfunctioning

Role-physical

Role-emotionalPhysicalfunctioningMentalhealthindexGeneralhealthperceptionsPainindex*ExpectedWorseLong-termQualityofLifeBunchTJ,WhiteRD,NEJM,2003Survival(Unadjusted)intheAVIDTrialProportionsurvivingPatientsatrisk 1,016 644 333 104Surviving(%)Defibrillatorgroup 89.3 81.6 75.4Antiarrhythmic-druggroup 82.3 74.7 64.1YearsNEJM337:1576,1997P<0.02DefibrillatorgroupAntiarrhythmic-druggroupCP971778-41CumulativeriskAmiodaroneICDPatientsatriskAmiodarone 331 304 285 240 204 173 152 123 89ICD 328 305 288 245 215 179 153 134 101D 3 1 3 5 11 6 1 11 12Monthspostrandomization1p=0.0722p=0.14CanadianImplantableDefibrillatorStudy(CIDS)SurvivalAnalysis:All-CauseMortalityCP971778-18TheMulticenterAutomaticDefibrillatorImplantationTrial(MADITI)CumulativeSurvivalP=0.009YearsfromrandomizationICDControlNYHAI,II,IIIPriorMIEF0.35InducibleVT196ptTimeDependenceofICDBenefitafterMIMADITIIsubstudyLVEF30%PriorMI1mo

(mean81mo)CumulativeSurvival

AdjustedforBLDifferencesSurvival

distribution

functionWilber:Circ,2004YearsSurvival

distribution

functionICDConventionalICDConventionalHR=0.97(0.51,1.81)HR=0.55(0.39,0.78)P=0.92P=0.001RemoteMI(18mo)RecentMI(<18mo)CP1215754-314,609ptVALIANTTrialSCD–7%SuddenCardiacDeathinPostMIPatients

Solomon:NEJM,2005CP1196896-3AveragetimefromMIenrollment5daysMonthsaftermyocardialinfarctionRateofsuddendeathorcardiacarrestwithresuscitation(%/mo)12345612243648DINAMITTrial–LackofBenefitfromICD

All-CauseMortalityCP1182269-1CumulativeriskP=0.66MonthsfromrandomizationICDControlRecentMI(6-40days)EF0.35HRV674ptHohnloser:NEJM,2005CausesofDeathAfterMIwithLVDysfunctionCP1200978-1OPTIMAALTrialLosartan/CaptoprilMI<10daysCHF/LVdysfunction180pt–autopsyreportSCD

14%MI

51%Other

29%CausesofDeath–AutopsyOrn:AJM,2005TotalMortalitySuddenDeathSuddenCardiacDeathinHeartFailureTrial(SCD-HeFT)

CumulativeRiskBardy:NEJM,2005YearsPlaceboICDP=0.05P=0.06EF0.35NYHAII,III52%ischemicDCM2521ptAmioAmioPlaceboICDCumulativeRiskTotalMortalitySuddenDeathDefibrillatorsinNon-IschemicCardiomyopathyTreatmentEvaluation(DEFINITE)TrialSurvivalKadish:NEJM,2004YearsSurvivalICDConventionalICDConventionalP=0.08P=0.006EF0.36NYHAI,II,IIIAmbientarrhythmias458ptTimeBenefitofICDtherapy

(DEFINITETrial)ICDControlICDControlP=0.049P=0.483Survival(Days)NIDCM<3mosNIDCM>3mosKadish:JACC,2005Annualrateofdeathfromanycausewithconventionaltherapy(%)DEFINITESCD-HeFTMADITIIMUSTTMADITICOMPANIONHazardRatioforRiskofDeath

ICDvsControlTherapyDINAMITCABGPatchEfficacyofICDforPrimaryPreventionSanders:NEJM,2005CP1234274-3Buxton:Circ,20021,791ptMUSTTtrialEF40%DocumentedCADRelationshipofEFtoModeofDeathCP1230337-1EjectionfractionEventrateRelationofEFtoTotalMortalityor

ArrhythmicDeath/CardiacArrestDeathArrhythmic

death/cardiacarrestCOMPANION

DeathfromAnyCause506070809010001202403604806007208409601080Event-freesurvival(%)DaysafterrandomizationPacemaker-defibrillator(105events,P=0.003)Pharmacologictherapy(77events)Pacemaker

(131events,P=0.059)BristowMR,SaxonLA,etal.NEJM2004;350:2140ImpactofCRTonAsymptomaticLeftVentricularDysfunctionat12monthsCRToffCRTon

LVESV

LVEDVEF-1.31.40.6-18.4-20.53.8All<0.0001LindeC.ACCLateBreakingClinicalTrials,2008MADIT-CRTMossAetal.NEnglJMed2009;10.1056/NEJMoa0906431QRS≥120QRS<120QRS≥120QRS<120QRS≥120QRS<120QRS≥120QRS<120PeakO2ConsumptionNYHAClassQOLScores6MinuteWalkp=0.24p=0.02p=0.63p=0.24p=0.31p=0.76p=0.04p=0.01ChangefromBaseline(%)ChangefromBaseline(%)ChangefromBaseline(%)ChangefromBaseline(%)MedianMedianRethinQStudy172Patients,StandardICDindication,QRS<130ms,mechanicaldyssynchronyBeshaiNEJM2007DistributionofLVEFCP1222765-3SuddenCardiacArrestwithNormalEFStecker:AHA,2006MultnomahCounty,Oregon202ptSurvivaltohospitaladmissionNormalEF.36-.54<36%42%38%20%AMI–42%AMI/ischemicsymptomsObstructiveCAD–61%Noevidenceofcoronaryischemia–22%RiskFactorReductionEffectivetreatmentofhypercholesterolemiaEffectivetreatmentofhypertensionAdoptionofaheart-healthydietRegularexerciseSmokingcessationModerationofalcoholconsumptionEffectivetreatmentofdiabetesYaggi,H.etal.NEnglJMed2005;353:2034-2041SuddenDeathwithObstructiveSleepApneaSurvivalYearsOSAControlsP=0.0301020304050Day-NightPatternofSCDProportionoftotalsuddencardiacdeaths(%)0:00-5:59Timeofday6:00-11:5912:00-17:5918:00-23:5921%41%26%12%NoOSA(n=34)16%30%29%25%GeneralpopulationP<0.001P=0.01P<0.001P=0.02P=0.0446%20%9%24%OSA(n=78)GamiAS,HowardDE,OlsonEJ,SomersVK.NEJM,2005Epidemiologyof“Asymptomatic”LeftVentricularSystolicDysfunctionWangTJ.AnnInternMed2003StrongHeartHyperGenDaviesMONICAEF<35MONICAEF<302.92.14.03.41.80.97.75.92.91.4EjectionFraction<0.4EjectionFraction<0.4(noCHF)UnderlyingDiseasesin“Asymptomatic”LeftVentricularSystolicDysfunctionWangTJ.AnnInternMed2003StrongHeart(n=444)SOLVDPrevention(n=2117)Davies(n=72)MONICA(n=43)DiabetesMIHTN193373152646157937TheconsumptionoffishandfishoilsuddendeathriskServingsoffishperweek02460.51.01.52.0RelativeRiskRelativeRiskN-3fattyacidintake,g/mo02460.51.01.52.0810Albert,CM,Hennekens,CH,O'Donnell,CJ,etal.JAMA1998;279:23.

AllintheGenes44PatientsPeripartumCardiomyopathy12NSVT/VT4q25-q27p=10-4to10-54q25-q27–encodesforaregionassociatedwithLongQTandtheSodiumChannelLimT,HorneB,BunchTJAfamilyhistoryofcardiacarrest,eitheraloneorwithmyocardialinfarction,isassociatedwitha1.5-1.8XincreasedriskofcardiacarrestArrhythmiasandCongenitalConditionsCP1052359-2LQTSBrugadasyndromeCPVTSQTSFamilialAFSSSHCMARVCDCMStructuralChannelopathiesRecommendationsforImplantable

Cardioverter-DefibrillatorsClassI(SecondaryPrevention)ICDtherapyisindicatedinptwhoaresurvivorsofcardiacarrestduetoVFiborhemodynamicallyunstablesustainedVTafterevaluationtodefinethecauseoftheeventandtoexcludeanycompletelyreversiblecauses(levelofevidence:A)CP1313975-9Epsteinetal:JACC51(21):2085,2008RecommendationsforImplantable

Cardioverter-DefibrillatorsClassIIaICDimplantationisreasonabletoreduceSCDinptwithlong-QTsyndromewhoareexperiencingsyncopeand/orVTwhilereceivingb-blockers(levelofevidence:B)ICDimplantationisreasonableforptwithBrugadasyndromewhohavehadsyncopeorVTwithoutcardiacarrest(levelofevidence:C)ICDimplantationisreasonableforptwithhypertrophiccardiomyopathywhohave1majorriskfactorforSCD(levelofevidence:C)CP1313975-13ModifiedfromEpsteinetal:JACC51(21):2085,2008RecommendationsforImplantable

Cardioverter-DefibrillatorsClassIIbICDtherapymaybeconsideredforptwithlong-QTsyndromeandriskfactorsforSCD

(levelofevidence:C)CP1313975-15ModifiedfromEpsteinetal:JACC51(21):2085,2008CP1255114-20ACC/AHA/HRS2008GuidelinesDeviceBasedTherapyforCardiacArrythmiasACC/AHA/ESC:Circulation2008ICDObserveTargetedTxObserveIschemicHeartDiseaseEF<35VF/VT

RecentMIorRevascularizationInheritedChannelopathy,HCM,ARVDOptimalMedManagementReversableCause?NoYesHighRiskFeaturesSyncopeObserve40daysTXRiskFactorsIC