我国心血管病介入进展培训教学课件

1、我国心血管病介入治疗进展内容冠心病介入治疗 国产DES的研发与应用 可降解血管内支架研发 分叉病变及左主干PCI研究结构性心脏病 经导管主动脉瓣置换术（TAVR） Parachute左心室隔离治疗心梗后心衰Evolution of DES Developed in China1st generation: 316L+durable polymer+sirolimus2nd generation:Changes in Stent Platform/polymer property/drug loading formatNewer generation:Changes in stent platf

2、orm-polymer-drug loading formatSince 2004Since 2006 FIM study in 2010 (TARGET I) Firebird SES Partner SES Excel SES Firebird 2 SES Tivoli SES Noya SES BuMA SES Helios SES Firehawk SESYinyi PESNano+ SESBicare dual drug DES2 : 1Primary EndpointIschemia-driven target lesion failure (i-TLF) which is a c

3、omposite of cardiac death, myocardial infarction (Q and non-Q wave) and ischemia-driven target lesion revascularization (i-TLR) at 12 months post-procedure Major Secondary Endpointi-TLF at 12-month after Tivoli implantation with 6- or 12-month DAPT2790 de novo CAD patientsTivoli GroupN=1860Firebird

4、2 GroupN=9306-month DAPTN=93012-month DAPTN=93012-month DAPTN=9306mo9mo4yr3yr2yr12mo5yr30dPrimary EndpointA Prospective, Multicenter, Randomized Trial to Evaluate the Safety and Effectiveness of TIVOLI Biodegradable Polymer-Based vs. FIREBIRD 2 Durable Polymer-Based Sirolimus-Eluting Stent for Treat

5、ment of Coronary Artery Disease in Real-World SettingClinical Follow-UpI-LOVE-IT 2I-LOVE-IT 2 Trial Patient Flow 2790 patients from 32 Chinese centers assessed for eligibility between Oct. 2012 and Jun. 201353 patients excluded:- 11 not receive interventions- 5 refused to participate - 37 not meet i

6、nclusion criteria2737 patients randomized (BP-SES versus DP-SES = 2:1)BP-SES1829 (100%)DP-SES908 (100%)BP-SES1829 (100%)DP-SES908 (100%)BP-SES1818 (99.4%)DP-SES905 (99.7%)Analysis setITT = 1829Analysis setITT = 90830d F/U12m F/U30d F/U6m F/U12m F/UAnalysis setsITT = 909ATS = 8536m F/UAnalysis setsIT

7、T = 920ATS = 9766-month DAPT for BP-SES909 12-month DAPT for BP-SES9206-month DAPT for BP-SES909 (100%)12-month DAPT for BP-SES920 (100%)6-month DAPT for BP-SES909 (100%)6-month DAPT for BP-SES902 (99.2%)12-month DAPT for BP-SES916 (99.6%)12-month DAPT for BP-SES920 (100%)908 allocated to DP-SES1829

8、 allocated to BP-SESXu B, Late Breaking Trial at TCT 2014Primary Endpoint: TLF at 1 Year(Cardiac Death, TVMI, and CI-TLR)Zone of noninferiorityPre-specified margin = 3.7%Primary Noninferiority Endpoint Met BP-SES(n = 1818)6.3%DP-SES(n = 905)6.1%Difference : 0.25%Upper 1-sided 95% CI: 2.17%Noninferio

9、rityP value=0.0002%00.51.04.02.53.03.5 -0.51.52.0Non-inferiorUpper one-sided 95% CIXu B, Late Breaking Trial at TCT 2014Cumulative Incidence of Events (%)Time since Index Procedure (Days)3603002401801206000108642BP-SESDP-SES6.3%6.1%Target Lesion Failure Through 1 YearPatients at Risk:Days06012018024

10、0300360BP-SES1829176617601754173517241708DP-SES908864860859856854849Log-rank P = 0.97 Xu B, Late Breaking Trial at TCT 2014TLF and Components at 1 YearCumulative Event Rates (%)P = 0.80P = 0.39P = 0.50P = 0.62115/181855/90566/181839/90548/181820/90513/18185/905 Xu B, Late Breaking Trial at TCT 2014B

11、uMA电子接枝eG技术保证涂层稳定性 载药层 eG技术涂层 316L不锈钢金属3.8-10m 200nm 0.1mm类似“嫁接”，电子接枝eG技术在支架金属与惰性涂层之间建立化学键连接，稳定牢固。底部惰性涂层与载药高分子间交错对插连接，如“编小辫”载药层结构稳定和完整，确保药物稳定释放PBMA:聚甲基丙烯酸正丁酯； PLGA:聚乳酸羟基乙酸* John Ormiston et al. Presentation at TCT 2004BuMA稳定涂层确保了促进血管内皮化BuMATM支架经压握或扩张后(1KV 130倍)BuMATM稳定的底部涂层确保了促进血管内皮化的基础防止支架压缩和扩张导致的涂

12、层断裂和剥脱，减少物理障碍。保证涂层药物稳定而完全释放BuMA-OCT Randomized TrialQian J, et al. EuroIntervention. 2014;10:806-814.Primary Endpoint: Incidence of Stent Strut Coverage at 3 Months In strut level analysis, the proportion of covered struts was significantly higher in the BuMA vs. the EXCEL group (A), while the propo

13、rtion of malapposed struts was significantly lower in the BuMA vs. the EXCEL group (B). Qian J, et al. EuroIntervention. 2014;10:806-814.Real-world patients eligible for coronary stenting were randomized in a 1:1 ratioPrimary Endpoint: 1-year TLF (composite of cardiac death, TVMI, and CI-TLR), power

14、ed for sequential non-inferiority and superiority testingSecondary Endpoints: acute success rates, individual TLF components, PoCE (composite of all cause death, all MI, and any revascularization), and ARC definite/probable stent thrombosis*TLF = target lesion failure; TVMI = target vessel myocardia

15、l infarction; CI-TLR = clinically indicated target lesion revascularization; PoCE = patient-oriented composite endpoint EXCELn=1175BuMAn=11756 months9 months1 year30 days2 years3 years4 years5 yearsStudy Design of PANDA IIIClinical EndpointsPrimary end-point will be presentedat late-breaking trial ,

16、TCT 2015, 11-12 am Oct. 14Co-Cr stent with groovesD,L-PLA absorbed after 6-9 mo and recover to metallic surfaceSirolimusPrinting technologyFIREHAWK ComponentsAn Abluminal Groove Filled Bioabsorbable Polymer Sirolimus-Eluting StentRedefining Safety from Redundancy FreeRedundancy Redundancy*Data of Sy

17、nergy was calculated from 3.0*16TARGET Clinical ProgramTARGET I Trial Enrollmentn=5109mo Angio F/U(=80%)1-Year Clinical F/U (=95%) and Annually up to 5 Years (n=1,010)Primary Clinical Endpoint: Device Oriented Composite of Cardiac Death, TVMI, or iTLR (Target Lesion Failure, TLF) at 1-Year (Objectiv

18、e Performance Criteria)Long FIREHAWK (33 and 38mm) Registry, n=50Workhorse Stent * Randomized Trialn=460XIENCE Vn=230FIREHAWKn=2309mo Angio F/U(=80%)FIM Enrollmentn=214mo Angio (95%) and OCT (70%) F/UTARGET II Registry Enrollmentn=730Clinical F/UONLY* RVD 2.254.0mm, Lesion Length=24mmTARGET I RCTPri

19、mary Endpoint: In-Stent Late Loss at 9-Monthmm-0.020.000.020.140.080.100.12-0.04Zone of non-inferiorityPre-specified margin = 0.13mm0.040.06FIREHAWK(N = 199)0.130.24XIENCE V(N = 202)0.130.18Primary Non-Inferiority Endpoint Met Non-inferiorDifference : 0.00 mm Upper 2-sided 95% CI: 0.04 mmNon-Inferio

20、rityP value =80%)1-Year Clinical F/U (=95%) and Annually up to 5 Years (n=1,010)Primary Clinical Endpoint: Device Oriented Composite of Cardiac Death, TVMI, or iTLR (Target Lesion Failure, TLF) at 1-Year (Objective Performance Criteria)Long FIREHAWK (33 and 38mm) Registry, n=50Workhorse Stent * Rand

21、omized Trialn=460XIENCE Vn=230FIREHAWKn=2309mo Angio F/U(=80%)FIM Enrollmentn=214mo Angio (95%) and OCT (70%) F/UTARGET II Registry Enrollmentn=730Clinical F/UONLY* RVD 2.254.0mm, Lesion Length=24mmPatient Flow1-Month Clinical F/U(n=1007; 100%)Protocol denied = 31-Year Clinical F/U(n=1003; 99.6%)Los

22、s of follow-up = 4TARGET I RCTFIREHWAK (n=227)TARGET I LongFIREHWAK (n=50)TARGET IIFIREHWAK (n=730)Total FIREHAWK Patients(n=1007)Xu B, Late-Breaking Trial at CIT2013TLF Components at 12 MonthsCumulative Event Rates at 12 Months (%)39/10035/100328/10039/10031/1003Xu B, Late-Breaking Trial at CIT2013

23、Objective Performance CriteriaPrimary Endpoint: TLF at 12 Months%12396780OPC Pre-SpecifiedObjective Value = 9.0%45Primary OPC Endpoint Met OPCPoint Estimate : 3.9% Upper 2-sided 95% CI: 5.3% OPC P value 0.0001Upper one-sided 95% CIOPC Pre-SpecifiedTarget Value = 6.5%Even Point Estimate 6 months (per

24、 guidelines)30d3mo4yr3yr2yr6mo12mo5yrClinical/TLFAngio/OCT176 Pts QCA SubsetClinical Trial DesignOpen label, non-inferiority trialAll patients with symptomatic CADeligible for DES implantation(no lesion/vessel limitations)Firehawk SESn = 828Xience EES n = 82850 Pts OCT Subset13mo内容冠心病介入治疗 国产DES的研发与应

25、用 可降解血管内支架研发 左主干PCI的研究结构性心脏病 经导管主动脉瓣置换术（TAVR） Parachute左心室隔离治疗心梗后心衰药物支架的未来-全降解药物洗脱支架药物洗脱支架（DES）通过抑制血管内膜过度增生减少再狭窄。但延迟内膜愈合，导致慢性炎症，增加晚期、极晚期支架内血栓形成。 支架在完成预防血管负性重构及释放抑制血管内膜增生的药物的功能之后（一般认为在6个月以后），其在血管内持久存在已无必要反而有潜在危害，影响正常血管运动，及日后在相同部位的血管重建（PCI或CABG）并干扰CT、MRI检查。因此全降解血管内支架的研制具有极大吸引力。多聚物降解支架，其中BVS多聚物（PLLA）Ev

26、erolimus (依罗莫司)降解支架临床试验取得满意结果。我国自行研制的多聚物降解支架的临床试验正在进行中 XINSORB ScaffoldP-DL-LA polymer carrying sirolimusRx. & balloon expandable1. PLLA bioresorbable compositions2. 150 m thickness3. Radial strength similar to BMS4. Sirolimus-eluting5. Available size: 2.75mm, 3.0mm and 3.5mm in diameter; 12mm, 15mm

27、, 18mm, 23mm and 28mm in lengthSirolimusFIM EvaluationPost-procedure 30days 90days 180days 270days 365daysClinical FU (N=30)Angiographic FU (N=30)Study objective: Prospective, bi-centers, first-in-human clinical trialPI: Prof. Junbo GEEnd point: Primary point: MACE at 30 days FU and LLL at 180 days

28、FU Secondary point: instantly device / procedure success, in-stent / in-segment restenosis, and TLRTreatment: Single de novo lesion with %DS50% and 100%, TIMI grade 1. Diameter of lesion 2.75mm 3.0mm Length of lesion must 14mm.Device sizes: Scaffold diameter: 3.0mm Scaffold lengths: 12, 15, 18mm6-mo

29、nth Angiographic FU (n=27)proximalIn-scaffolddistalDiameter of reference vessel (mm) After procedure3.040.292.920.292.670.35 6-month follow-up2.830.362.740.342.530.40 P value0.020.040.19Minimal luminal diameter (mm) After procedure2.850.342.620.252.470.38 6-month follow-up2.680.432.440.292.370.45 P

30、value0.110.020.36Acute gain (mm)1.430.43Late luminal loss (mm)0.170.300.180.210.100.32Diameter stenosis (%) After procedure6.85.610.04.27.27.1 6-month follow-up6.45.710.66.67.47.5 P value0.780.700.89In-scaffold LLL = 0.170.12 mmPeri-scaffold LLL = 0.130.24 mmClinical FUMACE = 0 6-month FUNo ARC conf

31、irmed/probable ST6-month OCT FU (n=19)1mmExcellent intimal healingLuminal area = 6.56 1.12 mm2 Scaffold area = 7.37 1.03 mm2 In-scaffold area obstruction = 11.3 4.2%Neointimal area = 0.83 0.48 mm2Neointimal thickness = 0.22 0.05mmNo stent thrombusNeoVasTM- Bioresorbable Sirolimus-Eluting Scaffold Sc

32、affold Material:- Bioresorbable Poly L-Lactic Acid (PLLA) Coating Carrier:- Bioresorbable Poly Lactic Acid (PDLLA) Sirolimus:- 15.3g/mmRadiopaque Markers:- PlatinumClinical Follow-up6 months9 months1 year30 days2 years3 years4 years5 yearsBaselineStudy DesignProspective, Two-Center, First-in-Man Stu

33、dy30 SubjectsObjectiveTo investigate the feasibility, preliminary safety and efficacy of the novel bioresorbable scaffold NeoVasTM in patients with de novo coronary artery diseasePrimary EndpointTLF (composite of cardiac death, TV-MI, iTLR) at 30 daysSecondary EndpointsLate lumen loss, minimal lumen

34、 diameter, diameter stenosis, binary restenosis by angiographic F/UMinimal/ mean vessel area, lumen area and scaffold area by IVUS assessmentIncomplete scaffold apposition, proportion of covered struts and thickness of struts coverage by OCT assessmentMSCT F/UAngio, IVUS, OCT F/UAngio, IVUS, OCT F/U

35、Angio, IVUS, OCT F/UMSCT F/UAngio, IVUS, OCT F/ULate Lumen LossPatrick W. Serruys, et al. Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis. Circulation. 2010, 122: 2301-2312. John A Ormiston, et al. A b

36、ioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet. 2008, 371:899-907.Han YL, Late Breaking Trial at CIT 201530 Days6 MonthsITT, n=31PPS, n=30ITT, n=31PPS, n=30All-Cause Death, % (n)0 (0)0 (0

37、)0 (0)0 (0) Cardiac Death, % (n)0 (0)0 (0)0 (0)0 (0) Non-Cardiac Death, % (n)0 (0)0 (0)0 (0)0 (0)Myocardial Infarction, % (n)0 (0)0 (0)0 (0)0 (0) Target Vessel MI, % (n)0 (0)0 (0)0 (0)0 (0)Any Revascularization, % (n)0 (0)0 (0)3.2 (1) 0 (0) TVR (non-TL) , % (n)0 (0)0 (0)0 (0) 0 (0) TLR, % (n)0 (0)0

38、(0)3.2 (1) 0 (0) Ischemia-Driven TLR, % (n)0 (0)0 (0)3.2 (1) 0 (0)TLF, % (n)0 (0)0 (0)3.2 (1) 0 (0)PoCE, % (n)0 (0)0 (0)3.2 (1) 0 (0)Def/Prob Stent Thrombosis, % (n)0 (0)0 (0)0 (0)0 (0)Clinical Outcomes Han YL, Late Breaking Trial at CIT 20153737 30d 6mo 9mo *12mo 24mo 36mo 48 mo 60 mo Clinical foll

39、ow-up Study Objective:Primary Endpoint:To evaluate the safety and effectiveness of the BVS in treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesionsIn-segment late loss at 1 year; non-inferiority to XIENCE VSecondary Endpoints: Various angiographic endpoin

40、ts & clinical endpoints XIENCE VN = 267XIENCE V / XIENCE PRIMEN = 1230 Up to two de novo native coronary artery lesions (single target lesion or one target and one non-target lesions, two target lesions, each in separate epicardial vessels)Lesion length 322322062011930123SS 22 849813802784SS 23-32 8

41、67785769750SS 32232201194190Cumulative Incidence of Events, %No. of Patients11.215.66.4Log-Rank P 32 SS 23-32 SS 22Log-Rank P = 0.005SS 32 SS 23-32 SS 22Time Since Index Procedure (Years)Log-Rank P = 0.003SS 32 SS 23-32 SS 220123SS 22 849833822810SS 23-32 867840826812SS 32232217214207Cumulative Inci

42、dence of Events, %All-Cause Death3.24.2Cumulative Incidence of Events, %Cardiac Death2.06.1Death/Stroke/MITVR8.23.3No. of PatientsCumulative Incidence of Events, %No. of Patients6.06.86.5Log-Rank P = 0.85SS 32 SS 23-32 SS 220123SS 22 849833822810SS 23-32 867840826812SS 32232217214207No. of PatientsC

43、linical Outcomes Through 3 YearsXu B, CIT 20153-Year All-Cause MortalityRevascularization Strategy According to Risk Prediction by SYNTAX ScoreOur data strongly support the recommendation from 2014 ESC/EACTS Guidelines on Myocardial Revascularization. Xu B, CIT 2015SYNTAX Score II - Combine Anatomic

44、al and Clinical CharacteristicsSYNTAX Score II nomogram for applicationLeft main=unprotected left main coronary artery diseaseFarooq, V., et al. Lancet. 2013. 0123SS-II 21 713673661647SS-II 22-28578531515498SS-II 286576115895700123SS-II 21 713679673664SS-II 22-28578528519505SS-II 286575925765550123S

45、S-II 21 713701697690SS-II 22-28578557549540SS-II 28657632616599Cumulative Incidence of Events, %No. of Patients10.214.05.20151050123Time Since Index Procedure (Years)Log-Rank P 0.0001200151050123Time Since Index Procedure (Years)Log-Rank P 0.0001200151050123Time Since Index Procedure (Years)Log-Rank

46、 P 28SS-II 22-28 SS-II 21 0123SS-II 21 713701697690SS-II 22-28578557549540SS-II 28657632616599Cumulative Incidence of Events, %All-Cause Death1.64.0Cumulative Incidence of Events, %Cardiac Death1.15.4Death/Stroke/MITVR7.32.8No. of PatientsCumulative Incidence of Events, %No. of Patients5.37.76.10151

47、050123Time Since Index Procedure (Years)Log-Rank P = 0.2620No. of PatientsSS-II 28 SS-II 22-28 SS-II 21 SS-II 28 SS-II 22-28 SS-II 21 SS-II 28 SS-II 22-28 SS-II 21 Clinical Outcomes Through 3 YearsXu B, CIT 2015AUC 95% CIHL (p value)Anatomical SYNTAX Score 0.592 0.526,0.6584.074 (0.85)Residual SYNTA

48、X Score0.547 0.485,0.609 5.145 (0.74)Clinical SYNTAX Score0.698 0.636,0.76013.55 (0.09)Logistic Clinical SYNTAX Score0.710 0.646,0.7736.41 (0.60)SYNTAX Score II for PCI0.675 0.616,0.7345.704 (0.68)AUC=Area under the curve; CI=confidence interval; HL=Hosmer-LemeshowDiscrimination and Calibration of S

49、YNTAX and Derived Scores for All-Cause Mortality 1-SpecificitySensitivityBaseline SYNTAX Score Residual SYNTAX Score Clinical SYNTAX Score Logistic Clinical SYNTAX Score SYNTAX Score II for PCI Reference LineXu B, CIT 2015内容冠心病介入治疗 国产DES的研发与应用 可降解血管内支架研发 左主干PCI的研究结构性心脏病 经导管主动脉瓣置换术（TAVR） Parachute左心室隔离治疗心梗后心衰The Venus A-ValveSevere AS: Echo-derived AVA 0.8 cm2 (or AVA index 2+Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA)Gao R, Euro-PCR 2015Patient E