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1、VinodH.Thourani,MDVinodH.Thourani,MDon behalf of The PARTNER Trial InvestigatorsThree-YearOutcomesafterTranscatheterorSurgicalAorticValveReplacementinHigh-RiskPatientswithSevereAorticStenosisACC 2013|San Francisco|March 11,2013Grant/Research SupportConsulting Fees/HonorariaMajor Stock Shareholder/Eq
2、uityOwnership/FounderIntellectual Property RightsEdwards Lifesciences,Sorin MedicalSorin Medical,St.Jude MedicalApica CardiovascularApica CardiovascularApica CardiovascularWithin the past 12 months,I or my spouse/partner have had a financial Within the past 12 months,I or my spouse/partner have had
3、a financial interest/arrangement or affiliation with the organization(s)listed below.interest/arrangement or affiliation with the organization(s)listed below.Affiliation/FinancialRelationshipCompanyDisclosureStatementofFinancialInterestDisclosureStatementofFinancialInterestBackgroundThe randomized P
4、ARTNER trial demonstrated that transcatheter aortic valve replacement(TAVR)resulted in similar mortality compared with surgical AVR at one year in patients who were high-risk surgical candidates.Longer term outcomes following TAVR are unknown and are necessary to assess valve performance and to anal
5、yze late complications before TAVR can be applied more widely.PublicationsinNEJM1-Yearoutcomespublishedon-lineJune5,2011NEJM.organdinprintJune9,20112-Yearoutcomespublishedon-lineMarch26,2012NEJM.organdprintMay3,2012Purpose In patients with severe AS at high-risk for surgery,randomized to either TAVR
6、 or surgical AVR,after 3 years follow-up,to assess:mortality,stroke and other clinical outcomes clinical and procedural predictors of mortality valve performance by echocardiographyN=179N=358InoperableStandardTherapyASSESSMENT:TransfemoralAccessNotInStudyTFTAVRPrimaryEndpoint:All-CauseMortalityOverL
7、engthofTrial(Superiority)Co-PrimaryEndpoint:CompositeofAll-CauseMortalityandRepeatHospitalization(Superiority)1:1Randomization VSYesNoN=179TFTAVRAVRPrimaryEndpoint:All-CauseMortalityat1yr(Non-inferiority)TATAVRAVR VS VSN=248N=104N=103N=244PARTNERStudyDesignSymptomaticSevereAorticStenosisASSESSMENT:H
8、igh-RiskAVRCandidate3,105TotalPatientsScreenedTotal=1,057patients2 Parallel Trials:Individually PoweredN=699HighRiskASSESSMENT:TransfemoralAccessTransapical(TA)Transfemoral(TF)1:1Randomization1:1RandomizationYesNoInclusionCriteria*Severe AS:Echo-derived AVA 0.8 cm2(or AVA index 40 mm Hg or peak jet
9、velocity 4.0 m/s Cardiac Symptoms:NYHA Functional Class IIHigh surgical risk:Predicted risk of operative mortality 15%(determined by site surgeon and cardiologist);guideline=STSScore10*Smith,C.R.,et al.,Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients.N Engl J Med,2011.36
10、4(23):p.2187-98.KeyExclusionCriteriaAortic annulus diameter(echo measurement)25 mmIliac-femoral anatomy precluding safe sheath insertion Severe LV dysfunction(LVEF 3.0 mg/dL or dialysis dependent Acute MI within 1 monthAcute MI within 1 month CVA or TIA within 6 monthsCVA or TIA within 6 months Hemo
11、dynamic instabilityHemodynamic instabilityClinical:Clinical:StudyDevicesEdwardsSAPIENTHV23 and 26 mm valves RetroFlex22 and 24 F sheathsAscendra24 and 26 F sheathsTransfemoralTransapicalEnrollingStudySitesIntermountainMedicalCenterSalt Lake City,UTEmoryUniversityAtlanta,GAUniv.ofMiamiMiami,FL Univ.o
12、fVirginiaCharlottesville,VA St.LukesHospitalKansas City,MOBarnes-JewishHospitalSt.Louis,MOMedicalCityDallasDallas,TXSt.PaulsHospitalVancouver,CanadaUniv.ofWashingtonSeattle,WAMayoClinicRochester,MNStanfordUniversityPalo Alto,CAHospitalLavalQuebec City,CanadaOchsnerFoundationNew Orleans,LAScrippsClin
13、icLa Jolla,CACedars-SinaiMedicalCenterLos Angeles,CAClevelandClinicCleveland,OHColumbiaUniversityCornellUniversityNew York,NYWashingtonHosp.CenterWash.,DCUniv.ofPennPhila.,PABrigham&WomensMassGeneralBoston,MANorthwesternUniv.Chicago,ILEvanstonHospitalLeipzigHeartCenterLeipzig,Germanyn=699 patients25
14、 investigator sites22 USA,2 Canada,1 GermanyKeyEnd-PointsAll-cause mortality(primary endpoint)All-cause mortality(primary endpoint)Cardiovascular mortalityCardiovascular mortalityRehospitalizationRehospitalizationStrokesStrokesVascular and bleeding eventsVascular and bleeding eventsNYHA functional c
15、lassNYHA functional classEchocardiographic measures of valve Echocardiographic measures of valve performance(including valve gradients/areasperformance(including valve gradients/areasand post-procedural aortic regurgitation)and post-procedural aortic regurgitation)StudyMethodology All patients follo
16、wed for at least three yearsAll patients followed for at least three years Primary analysis performed by intention-to-treat(ITT),Primary analysis performed by intention-to-treat(ITT),although as-treated(AT)analyses performed when although as-treated(AT)analyses performed when appropriate(e.g.echo da
17、ta=AT)appropriate(e.g.echo data=AT)Event rates as Kaplan-Meier estimates,with groups Event rates as Kaplan-Meier estimates,with groups compared by log-rank over the length of follow-upcompared by log-rank over the length of follow-up Composite analyses pre-specifiedComposite analyses pre-specified E
18、ffect of baseline variables on 3-yr mortality studied with Effect of baseline variables on 3-yr mortality studied with Cox proportional hazards regression(multivariable Cox proportional hazards regression(multivariable analysis with covariates p-value 0.20)analysis with covariates p-value 2mg/dL3710
19、.8226.4Atrialfibrillation8140.77543.6Pacemakerimplant6919.87621.8Pulmonaryhypertension12642.711136.8BaselinePatientCharacteristicsOtherCo-morbiditiesOtherCo-morbiditiesTAVR348298261239222187149AVR351252236223202174142All-CauseMortality(ITT)MonthspostRandomizationAll-CauseMortality0612182430360%10%20
20、%30%40%50%60%70%TAVRAVRNo.at RiskHR 95%CI=0.93 0.74,1.15p(log rank)=0.48326.8%24.3%34.6%33.7%44.8%44.2%All-CauseMortality(ITT)LandmarkAnalysisLandmarkAnalysisAll-CauseMortalityMonths3630241812600%20%40%60%80%100%Mortalitystartingat1yrAVRTAVRHR 95%CI=1.02 0.74,1.40p(log rank)=0.92226.8%24.3%10.7%12.4
21、%Numbers at RiskNumbers at RiskTAVRTAVR348348298298261261239239222222187187149149AVRAVR35135125225223623622322320220217417414214224.5%26.3%MultivariableBaselinePredictorsofMortality(ITT)TAVRTAVRHazardRatio95%CIp-valueBody Mass Index(lbs/in2)0.95 0.92,0.980.0003Atrial Fibrillation1.62 1.15,2.270.0056
22、Mean Gradient(Baseline)0.98 0.97,0.990.0033Liver Disease2.39 1.11,5.140.0254Renal Disease(CR 2)1.61 1.11,2.350.0131MultivariateBaselinePredictorsofMortality(ITT)AVRAVRHazardRatio95%CIp-valueCABG0.67 0.49,0.920.0139Pacemaker1.46 1.03,2.080.0353Moderate or Severe MR(Baseline)1.52 1.03,2.230.0330Liver
23、Disease2.34 1.09,5.040.0302STS Risk Score1.07 1.02,1.120.0048MultivariateBaselinePredictorsofMortality(ITT)PooledPooledHazardRatio95%CIp-valueBody Mass Index(lbs/in2)0.96 0.94,0.980.0002Atrial Fibrillation1.41 1.11,1.800.0050Mean Gradient(Baseline)0.99 0.98,1.000.0095Liver Disease2.38 1.39,4.090.001
24、6STS Risk Score1.04 1.01,1.070.0194TAVR AVRTAVR AVRTAVR AVRTAVR AVRTAVR AVR0%20%40%60%80%100%PercentofPatientsBaseline30Days2Years1Year94%15%94%24%15%13%17%35%348186205226250266307349IIIIIIIVNYHAClassSurvivors(ITT)p=0.001p=NSp=NSp=NS3Years133151p=NS14%19%No.at Risk34828725022821117613935124623021719
25、7169139TAVRAVRStrokes0612182430360%10%20%30%40%50%60%70%TAVRAVRStrokes(ITT)No.at Risk3.2%6.0%9.3%8.2%HR 95%CI=1.09 0.62,1.91p(log rank)=0.7634.9%7.7%MonthsPostRandomizationStrokes(AT)TAVRAVR348287250228211176139351246230217197169139TAVRAVRMonthspostRandomizationAll-CauseMortalityorStrokes06121824303
26、60%10%20%30%40%50%60%70%TAVRAVRAll-CauseMortalityorStrokes(ITT)All-CauseMortalityorStrokes(ITT)No.at RiskHR 95%CI=0.98 0.79,1.21p(log rank)=0.83928.6%27.4%36.1%36.9%45.9%47.1%1Year2Years3YearsOutcomeOutcomeAVRAVR(N=(N=351)351)TAVRTAVR(N=(N=348)348)p-valuep-valueAVRAVR(N=351)(N=351)TAVRTAVR(N=(N=348)
27、348)p-valuep-valueAVRAVR(N=351)(N=351)TAVRTAVR(N=(N=348)348)p-valuep-valueMajor Vasc.Comp.no.(%)no.(%)13(3.8)42(12.1)0.00113(3.8)43(12.5)0.00113(3.8)43(12.5)0.001Major Major Bleeding no.(%)Bleeding no.(%)88(26.7)88(26.7)52(15.7)52(15.7)0.0010.00195(29.5)95(29.5)61(19.3)61(19.3)0.0030.00399(31.5)99(3
28、1.5)64(20.8)64(20.8)0.0030.003New New PM no.(%)PM no.(%)16(5.0)16(5.0)21(6.4)21(6.4)0.440.4419(6.3)19(6.3)24(7.6)24(7.6)0.540.5420(6.8)20(6.8)25(8.1)25(8.1)0.560.56Endocarditis no.(%)3(1.0)3(1.0)2 2(0.6)(0.6)0.630.633(1.0)3(1.0)4(1.5)4(1.5)0.620.626(2.6)6(2.6)4(1.5)4(1.5)0.370.37SVD Requiring AVR0 0
29、0 00 00 00 00 0MI no.(%)2(0.6)00.164(1.5)00.056(2.7)2(1.1)0.23Acute Kidney Inj.*no.(%)20(6.5)18(5.4)0.5722(7.3)20(6.2)0.5923(7.9)22(7.2)0.76ClinicalOutcomesat1,2,and3Years(ITT)ClinicalOutcomesat1,2,and3Years(ITT)AllPatients(N=699)AllPatients(N=699)*Renal replacement therapy SVD=Structural Valve Dete
30、riorationEchocardiographicFindings(AT)AorticValveAreaAorticValveAreaTAVRAVRValveArea(cm2)Baseline30Days6Months1Year2Years3Years00.511.522.5TAVRAVRErrorbarsat1standarddeviationp=NSNo.of Echosp=0.0017p=0.0019p=NSp=0.0005p=NSp=NSp=NS3042712232111508829422616315412170EchocardiographicFindings(AT)Mean&Pe
31、akGradientsMean&PeakGradientsTAVRAVRGradient(mmHg)Baseline30Days6Months1Year2Years3Years01020304050607080PeakGradient-AVRPeakGradient-TAVRMeanGradient-AVRMeanGradient-TAVRNo.of Echos3102772332191558829923016915812372ParavalvularAorticRegurgitation(AT)ParavalvularAorticRegurgitation(AT)27922823017321
32、71581561228872PercentofevaluableechosTAVR AVRTAVR AVRTAVR AVRTAVR AVRTAVR AVR30Days6Months1Year2Years3Years100%80%60%40%20%0%NoneTraceMildModerateSevereNo.of Echosp 0.0001p 0.0001p 0.0001p 0.0001p 11MonthspostRandomizationMortality0612182430360%10%20%30%40%50%60%70%STS0-11STS11HR 95%CI=1.14 0.83,1.5
33、5p(log rank)=0.4191No.at Risk30.5%23.1%37.3%32.0%47.6%42.0%ImpactofSTSScoreonMortality(ITT)ImpactofSTSScoreonMortality(ITT)TAVRPatientsTAVRPatients177155141128117106871711431201111058162STS11STS11MonthspostRandomizationMortality0612182430360%10%20%30%40%50%60%70%STS0-11STS11HR 95%CI=1.38 1.02,1.88p(
34、log rank)=0.039No.at Risk28.8%19.9%36.1%31.4%49.1%39.6%Conclusions(1)At 3 years,in patients with symptomatic severe AS who were high-risk candidates for surgical AVR There was no difference in all-cause mortality between TAVR and surgeryBaseline predictors of mortality were different for TAVR(e.g.BM
35、I,PVD)and surgery(e.g.STS score,mod/severe MR)Symptom improvement was similar in both groups and maintained thru three yearsAt 3 years,strokes were similar in TAVR and surgery patients,despite increased peri-procedural neurologic events in TAVR patientsThere was no late(after 30 days)stroke hazard i
36、n TAVR compared with surgeryConclusions(2)Echocardiographic analysis revealedAt 3 years,TAVR hemodynamic performance was maintained with similar valve gradients and areas compared with surgeryBoth AVR and surgery resulted in significant LVEF improvement and LV mass regression Post-procedural paraval
37、vular AR was frequent after TAVR(mild-mod-severe 50%pts)without important changes during 3 year FUEven mild post-procedural AR(PVL and total AR)was associated with increased subsequent mortality Implications3-year results from the high-risk operable PARTNER cohort indicateTAVR should be considered a
38、n alternative to surgery with similar mortality and similar other major clinical outcomesPeri-procedural stroke concerns after TAVR have diminished with longer term follow-upTAVR valve hemodynamics have remained stable,although peri-procedural regurgitation(even mild)has emerged as a predictor of late mortalityFuture efforts should be directed towards reducing TAVR procedure-related complications,including strokes,vascular events,and paravalvular regurgitationThankyouPARTNERTEAM