TheU.S.ExperiencewithTotalArtificialHeartsvs.LeftVentricularAssistDevicesLyleD.Joyce,M.D.,PhD.DivisionofCardiovascularSurgeryTheMayoClinic,Rochester,MN,USADEBAKEYROLLERPUMP1954從實驗角度來說，用人工裝置代替心臟是可能的，這一點在動物身上已得到證實，實驗動物可以存活長達36小時。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域，那么人造心臟就能成為現(xiàn)實。——M.DeBakey1963美國國家心肺研究所開始實施美國人造心臟計劃（THEU.S.ARTIFICIALHEARTPROGRAM)1964WILLEMJ.KOLFF首個左室輔助裝置治療下康復病例

1966心臟支持輔助裝置的發(fā)展歷史心臟移植前類脈動式裝置完全人工或永久性支持設計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)流動裝置的出現(xiàn)

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

Randomized

Evaluationof

Mechanical

Assistanceforthe

Treatmentof

Congestive

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

285天(15-439)NumberofDays通過軸流改進裝置的小型化/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

有效支持時間(n=281)中位數(shù):155天(最長：5年)平均持續(xù)時間: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%的使用時間(140例年)為院外使用時間HeartMateII實際存活曲線

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

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的升高是唯一的獨立預測因素Potapov-Berlin17%RV衰竭54patients1998-2006Potapov–Berlin

RV衰竭的危險因素三尖瓣關閉不全右室的解剖形狀RV的后負荷脈動式和持續(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泵會2倍增加機械失效幾率無論結果怎樣，期望輔助裝置能更小,能效更高,可靠,植入易行,性價比更高,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