1、The U.S.Experience with Total Artificial Hearts vs.Left Ventricular Assist DevicesLyle D.Joyce,M.D.,PhD.Division of Cardiovascular SurgeryThe Mayo Clinic,Rochester,MN,USADEBAKEY ROLLER PUMP 从实验角度来说，用人工装置代替心脏是可从实验角度来说，用人工装置代替心脏是可能的，这一点在动物身上已得到证实，实验动能的，这一点在动物身上已得到证实，实验动物可以存活长达物可以存活长达3636小时。而且我敢肯定，如果小时
2、。而且我敢肯定，如果有足够的资金支持，尤其是在生物工程领域，有足够的资金支持，尤其是在生物工程领域，那么人造心脏就能成为现实。那么人造心脏就能成为现实。M.DeBakey美国国家心肺研究所开始实施 美国人造心脏计划（THE U.S.ARTIFICIAL HEART PROGRAM)WILLEM J.KOLFF首个左室辅助装置治疗下康复病例首个左室辅助装置治疗下康复病例 心脏支持辅助装置的发展历史心脏支持辅助装置的发展历史心脏移植前心脏移植前类脉动式装置类脉动式装置完全人工或永久性支持设计完全人工或永久性支持设计DeBakey VAD1966Liotta TAH1969Akutsu TAH 19
3、81Jarvik 7 TAH-1982AKUTSU TAH 的临床植入的临床植入Denton Cooley首例永久性首例永久性TAH植入植入里程碑式的转变里程碑式的转变:FDA通过了（通过了（LVAD）作为最终移植前的过渡治疗作为最终移植前的过渡治疗心脏大小差异带来的技术限制心脏大小差异带来的技术限制TCI-THORATEC LVADVictor PoirierNOVACOR-WORLD HEARTPeer Portner持续流动装置的出现持续流动装置的出现 SarnsBiomedicusIncidence of RVAD use0%5%10%15%20%25%1984-901991-9319
4、93-951996-971997-2000Year of ImplantIncidenceLinearised Rate of Right Ventricular Failure0.000.100.200.300.400.500.600-77-1414-3030Days after LVAS ImplantEvents/Recipient.monthREMATCH 试验 Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure充血性心力衰竭机械辅助治疗的随机化评估研究
5、充血性心力衰竭机械辅助治疗的随机化评估研究总体平均时间总体平均时间332 天天(15-632)流入瓣衰竭流入瓣衰竭408 天天(240-632)动力装置失效动力装置失效285 天天(15-439)3324082850100200300400500OverallInflow valvedysfunctionMotormalfunctionGeorge NoonHeartMate II2800 Patients Implanted 53 先期研究先期研究 488 移植前过渡治疗移植前过渡治疗商业性植入商业性植入Europe:Post CE Mark US:Post FDA Approval648
6、最终治疗最终治疗HeartMate II 全球临床研究全球临床研究 1136 主要研究主要研究 As of March 2009n=281(18 mo follow-up)Durations 413 1 year 241 1.5 year 188 2 yr 42 3 yr 3 4 yr 1 5yrDT 主要人群随访主要人群随访2年年 May 2009Cohorts:Randomized vs XVE XVE Exchange Small ptsFDA Approval Apr 2008 HeartMate II 临床研究 有效支持时间(n=281)中位数:155 天(最长：5年)平均持续时间:
7、237 天181 患者年累积支持87%患者出院77%的使用时间(140例年)为院外使用时间HeartMate II 实际存活曲线 Primary(n=133)and CAP(n=146)Cohorts12 mo:715%6 mo:774%Remaining at riskPrimary:133 48 32CAP:146 84 10 PRIMARYCAPAs of Sep 14,20076 mo:873%12 mo:756%Pagani et al AHA 2007HeartMate II 临床试验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%)
8、HeartMate II 临床研究致死因素(56/281)HeartMate II 临床研究不良事件HeartMate II 临床研究不良事件不良事件发生率比较HMII(n=281)vs HM VE BTT(n=280)11Frazier,Rose,Oz et al JTCVS 2001HeartMate II 无主要装置失效或置换事件率(BTT,n=281)6 mo:961%12 mo:932%18 mo:923%Remaining at risk281 131 72 52Pagani et al(submitted 2008)VentrAssistVentrAssistHeartWare
9、DuraHeartMatthews-Michigan35%LVAD患者出现右室衰竭患者出现右室衰竭共共197 例患者例患者1996 200668例例RV衰竭患者中衰竭患者中,58例为植入第一代例为植入第一代VAD患者患者,3 例为非脉动式例为非脉动式LVAD患者。患者。RV衰竭使衰竭使 LVAD患者的死亡几率增加了患者的死亡几率增加了6倍倍Dang -Columbia39%例出现例出现RV衰竭衰竭108 patients1996 2004CVP的升高是唯一的独立预测因素的升高是唯一的独立预测因素Potapov -Berlin17%RV衰竭衰竭54 patients1998-2006Potapo
10、v Berlin RV衰竭的危险因素衰竭的危险因素三尖瓣关闭不全三尖瓣关闭不全右室的解剖形状右室的解剖形状RV 的后负荷的后负荷脉动式和持续血流装置间无差异脉动式和持续血流装置间无差异Fitzpatrick -U Penn37%RV衰竭衰竭266 patients1995-2007RVFRS Risk(RV衰竭危险评分衰竭危险评分)需血管加压素需血管加压素 -4 分分AST 80 -2 分分胆红素胆红素 2.0 -2.5 分分肌酐肌酐 2.3 -3 分分AbioCor Implantable Components14例患者入选例患者入选4个中心个中心12例获得成功心脏支持例获得成功心脏支持2
11、例出院例出院支持作用时间支持作用时间:53-512 days (17 个月个月)累积支持：累积支持：5.2 例年例年2例围术期死亡例围术期死亡出血出血79 岁岁,二次手术二次手术,泵工作泵工作5小时余小时余肺动脉血栓形成肺动脉血栓形成弥漫的凝血病理改变弥漫的凝血病理改变,应应用血液制品用血液制品CardioWest Total Artificial Heart首例完全人工心脏移植首例完全人工心脏移植-Dr.Barney Clark完全人工心脏完全人工心脏左室辅助装置左室辅助装置左室辅助并短期右室辅助装置左室辅助并短期右室辅助装置(Hybrids)双室辅助装置双室辅助装置结论结论完全人工心脏：从
12、整体生理控制角度考虑，完全人工心脏：从整体生理控制角度考虑，具有一定优势具有一定优势心室辅助装置更容易接受心室辅助装置更容易接受两个泵会两个泵会2倍增加机械失效几率倍增加机械失效几率无论结果怎样，期望辅助装置能更小无论结果怎样，期望辅助装置能更小,能效能效更高更高,可靠可靠,植入易行植入易行,性价比更高性价比更高,而且最好而且最好能完全植入能完全植入(患者满意患者满意).英文原版The U.S.Experience with Total Artificial Hearts vs.Left Ventricular Assist DevicesLyle D.Joyce,M.D.,PhD.Divis
13、ion of Cardiovascular SurgeryThe Mayo Clinic,Rochester,MN,USADEBAKEY ROLLER PUMP“Experimentally,it is possible to replace the heart with an artificial heart,and animals have been known to survive as long as 36 hours.This idea,I am sure,could reach full fruition if we had more funds to support more w
14、ork,particularly in the bioengineering area.”M.DeBakeyNATIONAL HEART AND LUNG INSTITUTE ESTABLISHED THE U.S.ARTIFICIAL HEART PROGRAMWILLEM J.KOLFFFIRST SUCCESSFUL LVAD BRIDGE TO RECOVERY History of Cardiac Support DevicesPre-dates Cardiac TransplantationPulsatile DevicesDesigned for Weaning or Perma
15、nent SupportDeBakey VAD1966Liotta TAH1969Akutsu TAH 1981Jarvik 7 TAH-1982CLINICAL IMPLANTATION OF AKUTSU TAH Denton CooleyFIRST PERMANENT TAH IMPLANT Paradigm Shift:FDA Approval For Bridge to Transplantation Prior to Use as Destination TherapyTECHNICAL LIMITATIONS DUE TO SIZETCI-THORATEC LVADVictor
16、PoirierNOVACOR-WORLD HEARTPeer PortnerEMERGENCE OF CONTINUOUS FLOW DEVICES SarnsBiomedicusIncidence of RVAD use0%5%10%15%20%25%1984-901991-931993-951996-971997-2000Year of ImplantIncidenceLinearised Rate of Right Ventricular Failure0.000.100.200.300.400.500.600-77-1414-3030Days after LVAS ImplantEve
17、nts/Recipient.monthREMATCH Trial Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart FailureOverall Mean Time332 days(15-632)Inflow valve failure408 days(240-632)Motor Malfunction285 days(15-439)3324082850100200300400500OverallInflow valvedysfunctionMotormalfunctionG
18、eorge NoonHeartMate II2800 Patients Implanted 53 Pilot Study 488 Bridge to TransplantCommercial ImplantsEurope:Post CE Mark and US:Post FDA Approval648 Destination TherapyHeartMate II Worldwide Clinical Experience 1136 Pivotal Study As of March 2009n=281(18 mo follow-up)Durations 413 1 year 241 1.5
19、year 188 2 yr 42 3 yr 3 4 yr 1 5yrDT primary cohort with 2 year follow-up May 2009Cohorts:Randomized vs XVE XVE Exchange Small ptsFDA Approval Apr 2008 HeartMate II Clinical Study Support Duration(n=281)Median duration:155 days(longest:5.0 yr)Average duration:237 days181 pt-years cumulative support8
20、7%patients discharged78%on device support10%following transplant(prior to index discharge)77%of time(140 pt-years)spent out of hospitalHeartMate II Actuarial Survival Primary(n=133)and CAP(n=146)Cohorts12 mo:715%6 mo:774%Remaining at riskPrimary:133 48 32CAP:146 84 10 PRIMARYCAPAs of Sep 14,20076 mo
21、:873%12 mo:756%Pagani et al AHA 2007HeartMate II Clinical TrialPost-transplant Survival30 Days Post-Transplant150/157(96%)One year post-transplant117/128(91%)HeartMate II Clinical StudyCauses of Death(56/281)HeartMate II Clinical StudyAdverse EventsHeartMate II Clinical StudyAdverse EventsAdverse Ev
22、ent Rate ComparisonsHMII(n=281)vs HM VE BTT(n=280)11Frazier,Rose,Oz et al JTCVS 2001HeartMate II Freedom from Major Device Failure or Replacement(BTT,n=281)6 mo:961%12 mo:932%18 mo:923%Remaining at risk281 131 72 52Pagani et al(submitted 2008)VentrAssistVentrAssistHeartWare DuraHeartMatthews-Michiga
23、n35%RV failure after LVAD197 Patients1996 2006Of 68 cases of RV failure,58 occurred in first generation VAD,3 in non-pulsatile LVADPresence of RV failure adds 6 fold increase in odds of post-op LVAD deathDang -Columbia39%RV failure after LVAD108 patients1996 2004Elevated CVP was only independent pre
24、dictorPotapov -Berlin17%RV Failure54 patients1998-2006Potapov Berlin RV Failure Risk FactorsTricuspid incompetenceGeometry of RVRV after-loadNo difference between pulsatile and continuous flow devicesFitzpatrick -U Penn37%RV Failure266 patients1995-2007RVFRS Risk(RV failure risk score)Vasopressor re
25、quirement -4 pointsAST 80 -2 pointsBilirubin 2.0 -2.5 pointsCreat 2.3 -3 pointsAbioCor Implantable ComponentsFourteen Patients Enrolled at Four Centers12 successfully supported2 dischargedSupported duration:53-512 days (17 months)Cumulative support:5.2 patient years2 perioperative deathsBleeding79 y
26、r.,reop,5+hr.pump runPulmonary artery thrombosisprofound coagulopahy,given factor concentratesCardioWest Total Artificial HeartFirst Permanent Total Artificial Heart Implant-Dr.Barney ClarkTotal Artificial HeartsLeft Ventricular AssistsLeft Ventricular Assist with short term Right Ventricular Assist
27、(Hybrids)Biventricular AssistsCONCLUSIONTotal Artificial Hearts have the advantage when considering the value of full physiological controlVentricular Assist Devices have more emotional appeal.Two pumps could double the chance of mechanical failure.Whatever the outcome,the device(s)will have to be small,energy efficient,reliable,easy to implant,cost-effective,and hopefully totally implantable(patient satisfaction).
