心臟輔助器械發(fā)展-中英文課件

TheU.S.ExperiencewithTotalArtificialHeartsvs.LeftVentricularAssistDevicesLyleD.Joyce,M.D.,PhD.DivisionofCardiovascularSurgeryTheMayoClinic,Rochester,MN,USADEBAKEYROLLERPUMP1954從實(shí)驗(yàn)角度來說，用人工裝置代替心臟是可能的，這一點(diǎn)在動(dòng)物身上已得到證實(shí)，實(shí)驗(yàn)動(dòng)物可以存活長達(dá)36小時(shí)。而且我敢肯定，如果有足夠的資金支持，尤其是在生物工程領(lǐng)域，那么人造心臟就能成為現(xiàn)實(shí)。——M.DeBakey1963美國國家心肺研究所開始實(shí)施美國人造心臟計(jì)劃（THEU.S.ARTIFICIALHEARTPROGRAM)1964WILLEMJ.KOLFF首個(gè)左室輔助裝置治療下康復(fù)病例

1966心臟支持輔助裝置的發(fā)展歷史心臟移植前類脈動(dòng)式裝置完全人工或永久性支持設(shè)計(jì)DeBakeyVAD–1966LiottaTAH–1969AkutsuTAH–1981Jarvik7TAH-1982AKUTSUTAH的臨床植入1981DentonCooley1982首例永久性TAH植入里程碑式的轉(zhuǎn)變:FDA通過了（LVAD）作為最終移植前的過渡治療1984TCI-THORATECLVADVictorPoirier1984,1986NOVACOR-WORLDHEARTPeerPortner1984持續(xù)流動(dòng)裝置的出現(xiàn)

SarnsBiomedicusLinearisedRateofRightVentricularFailure0.000.100.200.300.400.500.600-77-1414-30>30DaysafterLVASImplantEvents/Recipient.monthREMATCH試驗(yàn)

Randomized

Evaluationof

Mechanical

Assistanceforthe

Treatmentof

Congestive

HeartFailure充血性心力衰竭機(jī)械輔助治療的隨機(jī)化評估研究植入到裝置失效時(shí)間總體平均時(shí)間 332天(15-632)流入瓣衰竭 408天(240-632)動(dòng)力裝置失效

285天(15-439)NumberofDays通過軸流改進(jìn)裝置的小型化/微型化1998GeorgeNoonHeartMateII>2800PatientsImplanted

53先期研究

488移植前過渡治療商業(yè)性植入Europe:PostCEMarkUS:PostFDAApproval648最終治療HeartMateII全球臨床研究

1136主要研究

AsofMarch2009n=281(18mofollow-up)Durations413>1year241>1.5year188>2yr42>3yr3>4yr1>5yrDT主要人群隨訪2年May2009Cohorts:RandomizedvsXVEXVEExchangeSmallptsFDAApprovalApr2008HeartMateII臨床研究

有效支持時(shí)間(n=281)中位數(shù):155天(最長：5年)平均持續(xù)時(shí)間:237天181患者年累積支持87%患者出院78%帶著支持裝置10%在心臟移植后(priorto

indexdischarge)77%的使用時(shí)間(140例年)為院外使用時(shí)間HeartMateII實(shí)際存活曲線

Primary(n=133)andCAP(n=146)Cohorts12mo:71±5%6mo:77±4%RemainingatriskPrimary:1334832CAP:1468410PRIMARYCAPAsofSep14,20076mo:87±3%12mo:75±6%PaganietalAHA2007HeartMateII臨床試驗(yàn)

移植后存活率移植后30天存活率150/157(96%)移植后一年存活率117/128(91%)HeartMateII臨床研究

致死因素(56/281)HeartMateII臨床研究

不良事件HeartMateII臨床研究

不良事件UseofRVADorextendedinotropeuse>14days,orstartingafter14days不良事件發(fā)生率比較

HMII(n=281)vsHMVEBTT(n=280)11Frazier,Rose,OzetalJTCVS2001HeartMateII無主要裝置失效或置換事件率(BTT,n=281)6mo:96±1%12mo:93±2%18mo:92±3%Remainingatrisk2811317252Paganietal(submitted2008)VentrAssistVentrAssistHeartWareDuraHeartMatthews-Michigan35%LVAD患者出現(xiàn)右室衰竭共197例患者1996–200668例RV衰竭患者中,58例為植入第一代VAD患者,3例為非脈動(dòng)式LVAD患者。RV衰竭使LVAD患者的死亡幾率增加了6倍Dang-Columbia39%例出現(xiàn)RV衰竭108patients1996–2004CVP的升高是唯一的獨(dú)立預(yù)測因素Potapov-Berlin17%RV衰竭54patients1998-2006Potapov–Berlin

RV衰竭的危險(xiǎn)因素三尖瓣關(guān)閉不全右室的解剖形狀RV的后負(fù)荷脈動(dòng)式和持續(xù)血流裝置間無差異Fitzpatrick-UPenn37%RV衰竭266patients1995-2007RVFRSRisk

(RV衰竭危險(xiǎn)評分)需血管加壓素-4分AST>80-2分膽紅素>2.0-2.5分肌酐>2.3-3分AbioCorImplantableComponentsThoracicUnitImplantedControllerImplantedTETCoilImplantedBattery14例患者入選4個(gè)中心CardioWestTotalArtificialHeart首例完全人工心臟移植

--Dr.BarneyClark前景如何??完全人工心臟左室輔助裝置左室輔助并短期右室輔助裝置(Hybrids)雙室輔助裝置結(jié)論完全人工心臟：從整體生理控制角度考慮，具有一定優(yōu)勢心室輔助裝置更容易接受兩個(gè)泵會2倍增加機(jī)械失效幾率無論結(jié)果怎樣，期望輔助裝置能更小,能效更高,可靠,植入易行,性價(jià)比更高,而且最好能完全植入(患者滿意).英文原版TheU.S.ExperiencewithTotalArtificialHeartsvs.LeftVentricularAssistDevicesLyleD.Joyce,M.D.,PhD.DivisionofCardiovascularSurgeryTheMayoClinic,Rochester,MN,USADEBAKEYROLLERPUMP1954“Experimentally,itispossibletoreplacetheheartwithanartificialheart,andanimalshavebeenknowntosurviveaslongas36hours.Thisidea,Iamsure,couldreachfullfruitionifwehadmorefundstosupportmorework,particularlyinthebioengineeringarea.”M.DeBakey1963NATIONALHEARTANDLUNGINSTITUTEESTABLISHEDTHEU.S.ARTIFICIALHEARTPROGRAM1964WILLEMJ.KOLFFFIRSTSUCCESSFULLVADBRIDGETORECOVERY1966HistoryofCardiacSupportDevicesPre-datesCardiacTransplantationPulsatileDevicesDesignedforWeaningorPermanentSupportDeBakeyVAD–1966LiottaTAH–1969AkutsuTAH–1981Jarvik7TAH-1982CLINICALIMPLANTATION

OFAKUTSUTAH1981DentonCooley1982FIRSTPERMANENTTAHIMPLANTParadigmShift:FDAApprovalForBridgetoTransplantationPriortoUseasDestinationTherapy1984TECHNICALLIMITATIONSDUETOSIZETCI-THORATECLVADVictorPoirier1984,1986NOVACOR-WORLDHEARTPeerPortner1984EMERGENCEOF

CONTINUOUSFLOWDEVICES

SarnsBiomedicusLinearisedRateofRightVentricularFailure0.000.100.200.300.400.500.600-77-1414-30>30DaysafterLVASImplantEvents/Recipient.monthREMATCHTrialRandomized

Evaluationof

Mechanical

Assistanceforthe

Treatmentof

Congestive

HeartFailureImplanttoFailureTimeOverallMeanTime 332days(15-632)Inflowvalvefailure 408days(240-632)MotorMalfunction 285days(15-439)NumberofDaysMINIATURIZATIONTHROUGH

AXIALFLOW1998GeorgeNoonHeartMateII>2800PatientsImplanted

53PilotStudy488BridgetoTransplantCommercialImplantsEurope:PostCEMarkandUS:PostFDAApproval648DestinationTherapyHeartMateIIWorldwideClinicalExperience

1136PivotalStudyAsofMarch2009n=281(18mofollow-up)Durations413>1year241>1.5year188>2yr42>3yr3>4yr1>5yrDTprimarycohortwith2yearfollow-upMay2009Cohorts:RandomizedvsXVEXVEExchangeSmallptsFDAApprovalApr2008HeartMateIIClinicalStudySupportDuration(n=281)Medianduration:155days(longest:5.0yr)Averageduration:237days181pt-yearscumulativesupport87%patientsdischarged78%ondevicesupport10%followingtransplant(priortoindexdischarge)77%oftime(140pt-years)spentoutofhospitalHeartMateIIActuarialSurvival

Primary(n=133)andCAP(n=146)Cohorts12mo:71±5%6mo:77±4%RemainingatriskPrimary:1334832CAP:1468410PRIMARYCAPAsofSep14,20076mo:87±3%12mo:75±6%PaganietalAHA2007HeartMateIIClinicalTrial

Post-transplantSurvival30DaysPost-Transplant150/157(96%)Oneyearpost-transplant117/128(91%)HeartMateIIClinicalStudy

CausesofDeath(56/281)HeartMateIIClinicalStudy

AdverseEventsHeartMateIIClinicalStudy

AdverseEventsUseofRVADorextendedinotropeuse>14days,orstartingafter14daysAdverseEventRateComparisons

HMII(n=281)vsHMVEBTT(n=280)11Frazier,Rose,OzetalJTCVS2001HeartMateIIFreedomfromMajorDeviceFailureorReplacement(BTT,n=281)6mo:96±1%12mo:93±2%18mo:92±3%Remainingatrisk2811317252Paganietal(submitted2008)VentrAssistVentrAssistHeartWareDuraHeartMatthews-Michigan35%RVfailureafterLVAD197Patients1996–2006Of68casesofRVfailure,58occurredinfirstgenerationVAD,3innon-pulsatileLVADPresenceofRVfailureadds6foldincreaseinoddsofpost-opLVADdeathDang-Columbia39%RVfailureafterLVAD108patients1996–2004ElevatedCVPwasonlyindependentpredictorPotapov-Berlin17%RVFailure54patients1998-2006Potapov–Berlin

RVFailureRiskFactorsTricuspidincompetenceGeometryofRVRVafter-loadNodifferencebetweenpulsatileandcontinuousflowdevicesFitzpatrick-UPenn37%RVFailure266patients1995-2007RVFRSRisk

(RVfailureriskscore)Vasopressorrequirement-4pointsAST>80-2pointsBilirubin>2.0-2.5pointsCreat>2.3-3pointsAbioCorImplantableComponentsThoracicUnitImplantedControllerImplantedTETCoilImplantedBatteryFourteenPatientsEnrolled

atFourCenters12succ