人工生物瓣膜的应用及策略.pptx

HANCOCK II 第二代生物瓣技术 Carpentier EdwardsPerimount Bioprostheses MagnavalvePERIMOUNTvalve CEP 保存方法 在压力下应用戊二醛 促进胶原纤维之间的交联胶原纤维交联可避免胶原纤维断裂胶原纤维断裂最终可以导致钙化形成 进而导致瓣膜失效 生理固定对Valsalva窦和瓣叶功能的作用 影响血流动力学和耐久性 减轻生物机械性失效 新鲜瓣叶 戊二醛固定方法的进步 放射显像 取出的猪生物瓣 LentzDetal InhibitionofMineralizationofGlutaraldehyde FixedHancockBioprostheticHeartValves In CohnLH GalucciV ed CardiacBioprostheses Proceedingsofthe2ndInt lSymp YorkMedBooks NY1982306 19 T6处理后 左 未处理 右 流出道面 在植入4个月后取出的Hancock瓣膜 标准瓣膜 right 和T6处理后的 left Aminogroup AOA法至少从三个方面减少钙化 降低了钙离子弥散到组织中的速度在戊二醛固定的组织上形成了性能良好且耐久性强的结合 共价结合 可能可以洗脱一些脂质 来自天然产生带油酸 AOA treated Non treated Duarte EmoryUniversity Atlanta GA 放射显像提示了钙化组织的位置 AOA处理的瓣膜及对照组的大体外观 Mosaic瓣羊研究 植入5个月后取出 第一代支架HKI聚丙烯 第二代支架HKII聚甲醛支架变薄圆形凸起侧高降低2mmX线可探查的环及孔 瓣环下缝合圈和瓣环下瓣架 瓣环上缝合圈和瓣环下瓣架 瓣环上缝合圈和瓣环上瓣架 瓣环内人工瓣 真正的瓣环上 Supra X Supra X 真正的环上环外瓣 SupraX 瓣孔面积 瓣架在孔内孔径相当于瓣架内径 瓣环内没有任何阻碍中央孔和瓣环面积匹配需要全新的测瓣概念 瓣环支架孔面积 Supra X 瓣环上缝合环 CEP HKII Mosaic 瓣膜开闭更接近真实人体瓣膜 拼合式生物瓣 牛心包瓣或猪瓣膜等 HancockII 二尖瓣位 安全 迅速 不挂线 主动脉瓣位 全球专利CINCHTM旋转收缩瓣角机制 其他产品 Hancock II二尖瓣 缝合圈与支架均置于环间 缝合圈置于环上支架置于环间 真正的环上瓣 Supra X 缝合圈与支架均置于环上的 测瓣 真正的环上瓣HKIIvs环内瓣CEP Hancock II测瓣器底部 HancockII生物瓣的内径 病人瓣环内径凸起 代表瓣膜支架柱的大小和位置 有助于确定正确植入方位 CEP的环内瓣测瓣器 HKII侧高 21mm 19 1mm 21mm 19 1mm 21mm HancockII内径20 5mm 23mm HKII瓣号 支架外径 HKII内径 病人瓣环内径23mmHancockII CEP瓣号 CEP支架外径 病人瓣环内径21mmCEP CEP外径21mm 病人瓣环21mm 性能对比 组成设计三个瓣叶都是无冠瓣瓣叶低压固定戊二醛 1mmHg接合处有牛心包保护减少瓣叶在织物上的磨损Celcon支架 比乙缩醛均聚物 HKII支架 的抗张强度小 柔软性差无抗钙化处理 Biocor生物瓣 连接处犹打结般 挡在流出道 跨瓣压差升高薄弱环节 是血栓形成和钙化的潜在发生位点 Biocor主动脉瓣 Epic Linx处理 仅采用乙醇 与Biocor相比 并没有减少钙化一项20周的利用小羊二尖瓣置换模型进行的研究 用于研究 BiocorvsEpic 的安全性和有效性 以及银的释放速率和营养不良性钙化的程度 结果 20周的羊模型无法检测出Epic和Biocor生物瓣之间钙沉积的差别 无有效远期数据 Langankietal JournalofHeartValveDisease 1998Nov 7 6 633 8 SJ说他们的侧瓣高只有11mm 但是过低的侧瓣高 更差的血流动力学 HancockII 侧高过低的瓣膜 mmHg 跨瓣压差 芬兰心脏中心因为高跨瓣压差停止使用Biocor转用低跨瓣压差的HancockII MykenP等 St JudeMedicalBiocor猪心瓣15年随访结果 心脏瓣膜疾病杂志 2000年第9卷415 422页 高跨瓣压差导致过早衰败 Biocor与HancockII15年瓣膜结构衰败率比较 Biocor Kirali Biocor Myken HKII HKII 1 MykenP Bech Hanssen PhippsB CaidahlK FifteenYearsFollowUpwiththeSt JudeMedicalBiocorPorcineBioprosthesis JHeartValveDis2000 9 415 4222 Davidet al LaterresultsofheartvalvereplacementwithHancockIIBioprosthesis TheJournalofThoracicandCardiovascularSurgery Vol121 Number2Pg268 2783 Kiralietal FifteenyearclinicalexperiencewiththeBiocorPorcineBioprosthesisintheMitralposition AnnThoracicSurgery2001 71 811 815 二尖瓣 主动脉瓣 Epic是什么 SJMEpic没有长期或短期的临床研究证据 Linx 抗钙化处理可能使血流动力学表现进一步降低 因为酒精可以逐渐使组织干燥和变硬 Linx 使用的是95 的酒精 研究未能证实经过Linx 处理的瓣膜比没有处理过的Biocor瓣膜具有任何优势 同时也没有人类研究证据 Epic只不过是额外增加了Linx 处理的Biocor瓣 ACCAHA指南对生物瓣使用的建议 AVR Patients 65 WithdiscussionwithsurgeonaboutstrongriskofreoperationversustheriskofanticoagulationWomenofchildbearingageMVR Patients 65who AreinsinusrhythmandWithdiscussionwithsurgeonaboutstrongriskofreoperationversustheriskofanticoagulationAnyage Patientswhowillnotorcannottakewafarinanticoagulation 病人年纪越大 耐久性越好 Patientages 不同病人年龄的换瓣选择 Mechanical Tissue PatientAge Averagepatientage Z AlHalees BGometza AAlSanel CMDuranBehavioroftheHancockIIBioprosthesisinYoungPopulation WorldSymposiumonHeartValveDisease 1999London FromtheKingFaisalSpecialistHospitalandResearchCentre Riyadh SaudiArabiaandInternationalHeartInstituteofMontanafoundation Missoula Montana USA HANCOCK II PerformanceinPatientsAges11 40 BenefitsofPhysiologicFixation PhysiologicFixation PressureFixation Hingesite PhysiologicFixation Supra X Positioning Supra X positioningensurestheMosaicbioprosthesisisseatedsupra annularlywhilealigningtheinternaldiameterofthevalvewiththepatient sannulusNointra annularcomponentIncreasesareaavailabletoflow Intra annularsewingringwithintra annularvalve Supra annularsewingringwithintra annularvalve TrueSupra annular Supra X Supra annularsewingringwithsupra annularvalve Intra annularvalves Supra annularvalve Supra X Positioning 经导管肺动脉瓣膜 PhilippeBonhofer 90年代后期可用 首次在人类应用 可以为婴儿赢得时间 可以延后接受外科手术的时间 上腔静脉路线 从10月1日起已经超过800例病人 经导管主动脉瓣膜置换 CoreValve 可能还有更多 Cribier Edwards REFERENCES1Riess FCetal HemodynamicPerformanceandClinicalFollow upoftheMedtronicMosaicBioprosthesisupto12Years ABSTRACT presentedattheSHVD NewYork NY 2007 BanburyMKetal Long TermResultsoftheCarpentier EdwardsPericardialAorticValve A12 YearFollow Up AnnThoracSurg1998 66 S73 6 BanburyMKetal AgeandValveSizeEffectontheLong TermDurabilityoftheCarpentier EdwardsAorticPericardialBioprosthesis AnnThoracSurg2001 72 753 7 Confidential MitralRegurgitation PossibleReasons IthasaholeinitUnequalleafletelasticityLowstentpostsCausesleafletcoaptationzonetobeverysmall Triangleofleak CEPValve SizingandImplantation SizingImplantInflowView HancockII CEP StentID StentID StentOD AnnulusStentOrificeArea Notallsizersarethesame Notallsizersarethesame Upsize PlasticismoreFlexiblethanMetal HancockIIvalvePlastic acetalhomopolymer stent Lowmemoryandflexible CEPMetalstentMetalhasmemoryandcanbreak Plastic Metal VS CEPIFU Duetotherelativeflexibilityoftheframe caremustbeexercisedtopreventfoldingordeformationofthestent thatmightleadtoregurgitation alteredhemodynamics and orleafletdisruptionrenderingthevalveincompetent EaseofImplantAorticPosition CINCHTMHolderProfileComparison 23mmCarpentier EdwardsPerimount 23mmHII withtheCINCHTM EaseofImplant CINCHTMInAortaProfileComparison HemodynamicComparisonEOA HemodynamicComparisonMeanGradientMosaic HemodynamicComparisonMeanGradientCEP WeightedaverageofMeanGradient PORCINEvsPORCINE Whatmakesadifference SJMBiocor StentedTissueValve BiocorisaregisteredtrademarkofSt JudeMedicalInc Biocor Epic History1978BiocorporcinevalvedevelopedbyDr MarioVrandecicinBrazil 1982Biocorvalvereleased 1996September SJMacquiresBiocortissuevalvecompany 1998BiocorreceivesCEMark 2003USclinicalstudybeginsontheSJMEpic withLinx AC2003EuropeanlaunchoftheEpicSupra 2004FirstNorthAmericanimplantofitsSJMEpic Supravalve 2005August8thBiocorapprovedforsaleinUnitedStates ValveFeatureComparison CompositedesignThreenon coronarycuspsLowpressurefixationGlutaraldehyde 1mmHgPericardialshieldontheoutflowedgereduceleafletabrasionagainstfabricCelconstent lowertensilestrengthandlessflexiblethanacetalhomopolymer HKIIstent Noanti calcificationtreatment Biocorbioprostheses Epic Linxtreatment justethanol noreductionincalcificationvsBiocorA20 weekjuvenilesheepmitralvalveimplantmodelwasusedtodeterminesafetyandefficacyofthedevice BiocorvsEpic aswellastherateofsilverreleaseanddegreeofdystrophiccalcification Results the20 weeksheepmodelunabletodetectdifferencesincalciumaccumulationbetweentheEpicandtheBiocor Nolong termdataavailable Langankietal JournalofHeartValveDisease 1998Nov 7 6 633 8 Biocor Howisitproduced Hemodynamics Notallporcinevalvesarethesame Biocor LowerProfile WorseHemodynamics FeaturesProfile LeafletsAreSTUFFEDintostentsthataretoosmallHigherleafletstressesLeafletprotrusion Pericardialshieldobstructingflowarea Shieldinhibitsleafletsfromopeningfully BiocorAorticValve Stressfoldsareevidentradiatingfromthebaseofthecommisuresaswellascoaptationmis alignment Biocor HKII Mosaic AcceptableHemodynamics Myk nPSetal LONG TERMDOPPLERECHOCARDIOGRAPHICRESULTSOFAORTICORMITRALVALVEREPLACEMENTWITHBIOCORPORCINEBIOPROSTHESIS JThoracCardiovascSurg1998 116 599 608 Wouldgradientsofupto60mmHgbeacceptablewithaMosaicorHancockII Durability Notallporcinevalvesarethesame Anotherwaytolookatthedata ComparisonofSVDbetweenBiocorandHancockIIat15yrs Biocor Kirali Biocor Myken HKII HKII 1 MykenP Bech Hanssen PhippsB CaidahlK FifteenYearsFollowUpwiththeSt JudeMedicalBiocorPorcineBioprosthesis JHeartValveDis2000 9 415 4222 Davidet al LaterresultsofheartvalvereplacementwithHancockIIBioprosthesis TheJournalofThoracicandCardiovascularSurgery Vol121 Number2Pg268 2783 Kiralietal FifteenyearclinicalexperiencewiththeBiocorPorcineBioprosthesisintheMitralposition AnnThoracicSurgery2001 71 811 815 VS ClinicalComparison ComparisonofSVDbetweenBiocorandHancockIIat20yrs Implantability Notallporcinevalvesarethesame TheCinchMakesADifference TheBiocorplasticstentislessflexiblethantheHKIIstent TheBiocorstentpostareunabletodeflectaswellastheHKIIstentpost TheBiocorhasabulkyholderwhichmakesitdifficultforthesurgeontovisualizeandtosecuretheknotsduringtheprocedure Biocor HancockII Theory ReducesglutaraldehydetoxicityRemovescholesterolandlipidsReducesuptakeoflipidsfromthepatientintotheprosthesisTesting Connolly LevyRJetal JHeartValveDis2004 13 3 487 93 Vyavahare LevyRJetal JBiomedMaterRes199840 577 585 Flameng etal AnnThoracSurg2001 71 S401 5 Langanki etal JHeartValveDis1998 7 633 638 Shoen LevyRJetal AnnThoracSurg2005 79 1072 80 Linx Technology WhatweknowaboutLinx TheLinx anticalcificationtreatmentisasimple95 ethanoltreatment TheLinx treatmenthasbeendevelopedbyDr RobertLevyattheUniversityofMichiganandislicensedbySJM 21 dayratsubdermaltestswereperformed Nohumanstudies 20 dayjuvenilesheepstudiesshowednodifferencethanuntreatedBiocorsamples Studiesfoundabnormallyhighamountsofcuspalhematomas ProofSource Vyavahare2000Paper Ourinitialstudiesexploredethanolpretreatment butonlyafterglutaraldehydefixation Wealsodidnotexaminequestionsofstorageinglutaraldehydesolutionafterethanolpretreament Inconclusion glutaraldehydestoragefollowingethanolpretreatmentofglutaraldehyde fixedbioprostheticheartvalvesnegatesinhibitionofcalcification andwouldappeartobecontraindicatedinthefabricationofsuchvalvesforclinicaluse Vyavahare etal Preventionofglutaraldehyde fixedbioprostheticheartvalvecalcificationbyalcoholpretreatment furthermechanisticstudies JHeartValDis2000 9 4 561 6 WheredoesthatleaveEpic Thereisnolongorshort termclinicaldataavailableontheSJMEpic Linx anticalcificationtreatmentmightfurtherreducehemodynamicperformancesincealcoholgenerallydriesandstiffensthetissue Linx is95 ethanol StudieshavenotbeenabletoprovethatvalvestreatedwithLinx performedanybetterthannon treatedBiocorvalves Noranyhumanstudies EpicissimplytheBiocorvalvewiththeadditionofLinx SJM说生物瓣侧瓣越低越好 真是这样吗 生物瓣Newsletter 两种不同的猪主动脉瓣 完整猪主动脉瓣 瓣叶组合瓣 完整的猪主动脉瓣和人主动脉瓣膜结构对比 DataSource FDAApprovedInstructionsforUse 主动脉血流动力学 FDA审批IFU数据 术后一年平均跨瓣压差比较 侧瓣越低 瓣叶张力越大 20年生存率和耐久性的比较 MDTConfidential 86 总结 HKII采用猪的完整主动脉瓣 解剖更加接近人体瓣膜结构 瓣叶运动更符合生理情况Biocor降低了侧瓣高度 导致瓣叶无法完全打开 牺牲了血液动力学生物瓣侧瓣越低 瓣叶承受的张力越大 耐久性下降 而耐久性是生物瓣最重要的考虑因素美敦力的CINCH技术 能有效地避免二尖瓣植入时造成的心肌损伤 只要植入角度符合要求 左室流出道受阻极少发生 竞争对手临床实验比较 FreedomFromSVD比较 耐久性总结 60岁及以上患者FFSVD85 60岁及以上患者AVRFFSVD88 65岁及以上患者AVRFFSVD97 指南建议年龄生物瓣患者首选 患者生存率 生存率为什么重要 一切数据结果的基础 免予结构性衰败率FFSVD 60 70岁患者植入20年总体FFSVD85 主动脉FFSVD88 60 70岁患者植入20年总体FFRSVD90 主动脉FFRSVD92 瓣膜的分类 HKII和Perimount瓣叶重叠区域对比 HKII Perimount Deepercoaptation Shallowcoaptation MedtronicMosaicAorticandMitralBioprosthesis FifteenYearClinicalCompendium Medtronic Inc 2012 CarloValfre etal ThefateofHancockIIporcinevalverecipients25yearsafterimplant EuropeanJournalofCardio thoracicSurgery38 2010 141 146BanburyMK etal AgeandValveSizeEffectontheLong TermDurabilityoftheCarpentier EdwardsAorticpericardialBioprosthesis AnnThoracSurg2001 72 753 7 Carpentier EdwardsPERIMOUNTMitralPericardialBioprosthesisCommuniqu Model6900 2003EdwardsLifesciencesLLC Mosaic是二尖瓣耐久性最好的生物瓣 生物瓣衰败原因 物理性因素 血流冲击撕裂等 压力 组织原因 瓣膜结构衰败 化学性因素 固定剂钙化 SchoenF LevyR TissueHeartValves CurrentChallengesandFutureResearchPerspectives JBiomedMaterRes 47 439 465 1999 如何对抗两种瓣膜失效原因 改进瓣架设计 生物机械性 改进戊二醛处理和压力固定技术 生物机械性 使用抗钙化剂 生物化学性 CINCHII有效的保护心室纵向环 PERIMOUNTTHEON MODEL6900PTFX MAGNAMITRALEASE MODEL7300TFX ThermaFixprocess BioengineeredFlexibleCoCralloystentPericardialleaflets ThermaFixprocess BioengineeredFlexibleCoCralloystentPericardialleaflets Supra annulardesignLowestprofile Easeofimplant EdwardsMitral Edwards宣传卖点 经过大量临床数据验证的血液动力学EOA 平均跨瓣压差为耐久性而设计独特的ThermaFix工艺提高了瓣膜的长期性能安全易于植入Tricentrix传送系统 St JudeMedicalBiocor Epic StentedTissueValves Biocor特点 三片独立瓣膜 无冠瓣 组合瓣 FlexFit System LinxAC去钙化功能 瓣架 由于支架过低 留给瓣叶的空间过于狭小瓣叶承受更高压力瓣叶更突出 无法保持自然形态 低瓣架设计与血流动力学 St JudeBiocor 带支架生物瓣 BiocorisaregisteredtrademarkofSt JudeMedicalInc Biocor Epic 复合瓣叶设计由三片独立裁剪的无差异瓣叶组成低压固定技术固定压力小于1mmHgGlutaraldehyde 1mmHg流出道瓣脚边缘心包保护减少瓣叶与纺织物之间的摩擦Celcon材料支架 低强度 低弹性支架 与HKII支架相比较 无抗钙化处理 Biocor人工生物瓣膜 Epic人工生物瓣膜 Linx抗钙化试剂主要成分 无水酒精 没有带来比Biocor更好的抗钙化效果一项针对Biocor和EPIC抗钙化效果试验的结果显示 在小羊体内植入Biocor和EPIC二尖瓣 20周后 EPIC在钙离子沉积效果上 与Biocor并无差异 缺乏长期临床数据支持 Langankietal JournalofHeartValveDisease 1998Nov 7 6 633 8 抗钙化能力 6周之后 5 5Magna发生钙化中心留有缝隙1 5Mosaic发生钙化 abcdefg OpeningandClosingkinematics Magna top andMosaic bottom Calcium 扩大1个瓣号 Increaseingradientobservedwheninflowofvalveisobstructed 新测瓣器使用步骤 第一步 使用测瓣器桶端测量瓣膜大小 Ifthepotentialexistsfor a valveprosthesisinterferencewithcoronaryostia b tissueobstructiontovalveprosthesisinflow or c deformationofthevalveprosthesisstent considerreorientationofthevalve selectingasmallervalvesize oraddressingtheobstructionorinterferencesurgically 此例显示 25mm瓣膜对23mm瓣膜的比较 新Mosaic测瓣器 ReplicaEnd BarrelEnd DONOTCOPY NOTFORDISTRIBUTION Theclosingproblem Strokevolume80ml 6weeks 4l 40bpm highstrokevolumeof80ml MOSAICULTRA MAGNA NodesofArantius NaturalandporcinevalveshavethenodesofArantiuswherethreecuspcoaps pericardialvalvesdoNOThavethis Pericardialvalvehaveopeninginthecenterofleafletstocompensatetheleafletabrasion Naturalvalve Porcinevalve Pericardialvalve 术后1 5年返流对比 Mitral RegurgitationinCEPvalves Banburyetal AnnThoracSurg2002 73 1460 5 After12years 50 ofthesepericardialvalvesshowednoneortrace trivial regurgitation30 showedmildregurgitationandtheremaining20 moderatetosevere AVRMVR5yrs11yrs5yrs10yrs n 161 n 11 n 25 n 9 none87 063 696 0100trivial8 127 3 mild4 39 14 0 moderate0 6 severe RiessFC BaderR CramerE HansenL WahlG WinkelS BleeseNAlbertinenHeartCenter Hamburg MosaicData 90 9 noneortrivialregurgitationforAortic 血流动力学对比总结 Mosaic和HKII接近生理结构 牛瓣设计缺陷存在返流危险Mosaic HKII开合速度优于牛瓣 更符合生理条件下瓣膜特点开口面积不是血流动力学唯一决定因素 返流同样增加心肌能量损耗Mosaic HKII和牛瓣在瓣号选择上存在错位 相同条件下 Mosaic HKI