左心耳封堵术应用进展韩宝石课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,房颤与脑卒中,3300,万,房颤患者,抗凝,房颤是最常见的心律失常,房颤会增加卒中率,左心耳血栓,90%,NVAF,患者的血栓来源于左心耳,45%,未正规服用华法林抗凝,1 Chugh,S et al.Circulation,2014;129:837-847,2 Holmes DR,Atrial Fibrillation and Stroke Management:Present and Future,Seminars in Neurology 2010;30:528536.,3 Blackshear JL.Odell JA,.,Annals of Thoracic Surgery.,1996;61:755-759,4 Waldo,AL,.JACC,2005;46:1729-1736./Holmes DR et al,Atrial Fibrillation and Stroke Management:Present and Future,Seminars in Neurology 2010;30:528536,节律或心率,起搏器,药物控制,卒中或栓塞,华法林,左心耳,结扎,封堵,消融,新型口服抗凝药,达比加群,利伐沙班,阿哌沙班,房颤治疗,房颤治疗策略,问题一：传统或新型口服抗凝药物，预防房颤患者卒中的“真实世界”情况？,Piccini,et al.Pharmacotherapy in Medicare beneficiaries with atrial fibrillation.Heart Rhythm.2012;9:1403-1408,据统计，高危患者人群华法林应用率不足,60%,。,CHADS,2,评分,(n=27,164),房颤患者华法林使用率,华法林,-5,-,-4,-,-3,-,-2,-,-1,INR,过度抗凝,抗凝不足,治疗剂量,44%,出血病人,INR,超过,3.0,48%,血栓栓塞病人,INR,小于,2.0,1,现状：,许多患者,INR,控制不佳，多数时间不在治疗剂量。,在美国，华法林是老年人因药物副作用而急诊住院最常见的,药物,2,。,华法林,1 Oake N,et al.Can Med Assoc J.2007:176(11);15891594,2 Budnitz,MD,MPH.et al.Annals of Internal Medicine.2007:147(11);229,1 Glazer NL,Arch Intern Med(2007),2 Shen AY,J Am Coll Cardiol(2007),3 Go AS,JAMA(2003),华法林控制,INR,要求很高，需要评估权衡卒中和出血风险。,只有约,50%,服用华法林的患者达到了治疗剂量的抗凝强度。,不在治疗剂量的患者会面临高的出血,/,缺血性卒中风险,华法林,新型口服抗凝药,达比加群,1,利伐沙班,2,阿哌沙班,3,对照组,华法林,华法林,华法林,总入选病例数,18,113,14,264,18,201,随访时间,2,年,1.94,年,1.8,年,平均,CHADS,2,评分,2.1,3.5,2.1,结果,(,首要终点为卒中或系统栓塞,),较华法林降低,较华法林降低,较华法林降低,1 Connelly SJ et al,NEJM,2009;361:1139-51,2 Patel MR et al,NEJM,2012;365:883-91,3 Granger,J MD.,NEJM,2012;365:981-92,治疗药物,药物治疗中断率,年大出血率,利伐沙班,1,24%,3.6%,阿哌沙班,2,25%,2.1%,达比加群,3,(150 mg),21%,3.3%,依度沙班,4,(60 mg/,30 mg),33%/34%,2.8%/1.6%,华法林,1-4,17 28%,3.1 3.6%,新型口服抗凝药,1Connolly,S.NEJM 2009;361:1139-1151 2 yrs follow-up(Corrected),2Patel,M.NEJM 2011;365:883-891 1.9 yrs follow-up,ITT,3Granger,C NEJM 2011;365:981-992 1.8 yrs follow-up,4Giugliano,R.NEJM 2013;369(22):2093-2104 2.8 yrs follow-up.,出血风险、抗凝效果仍不能令人满意,问题二：房颤患者抗凝治疗的问题，是否有替代办法或解决方案？,作者,病人数,随访时间,人群预估卒中发生率,植入封堵器后,实际卒中发生率,Block,1,64,5 years,6.6%,3.3%,Park,2,73,2 years,5.0%,0.0%,Ussia,3,20,40 10 months,6.4%,0.0%,De Meester,4,10,3 47 months,7.1%,0.0%,Ostermayer,5,111,9.8 months,6.3%,2.2%,Block,P.C.,Burstein,S.,Casale,P.N.,Kramer,P.H.,Teirstein,P.,Williams,D.O.,&Reisman,M.(2009).Percutaneous left atrial appendage occlusion for patients in AF suboptimal for warfarin therapy:5-year results of the PLAATO(Percutaneous Left Atrial Appendage Transcatheter Occlusion)Study.,JACC Cardiovascular Interventions,2,594-600.,Park,J.W.,Leithuser,B.,Gerk,U.,Vrsansky,M.,&Jung,F,.(2009),Percutaneous left atrial appendage transcatheter occlusion(PLAATO)for stroke prevention in AF:2-year outcomes.,Journal of Invasive Cardiology,21,446-50.,Ussia,G.P,.,Mul M,Cammalleri V,Scarabelli M,Barbanti M,Imm S,Mangiafico S,Marchese A,Galassi AR,Tamburino C.,.(2009,).Percutaneous closure of left atrial appendage to prevent embolic events in high-risk patients with chronic atrial fibrillation.,Catheter,Cardiovascular Interventions,74(2):217-22,.,De,Meester,P.,Thijs,V.,Van Deyk,K.,&Budts,W.,(2010).,Prevention of stroke by percutaneous left atrial appendage closure:short term follow-,up.,International,Journal of Cardiology,142,195-196.,Ostermayer,S.H.,Reisman,M.,Kramer,P.H.,Matthews,R.V.,Gray,W.A.,Block,P.C.,Sievert,H.(2005).Percutaneous left atrial appendage transcatheter occlusion(PLAATO system)to prevent stroke in high-risk patients with non-rheumatic AF:results from the international multi-center feasibility trials.,Journal of the American College of Cardiology,46,9-14.,左心耳封堵,-,来自,PLAATO,的证据,第一个,LAA,封堵装置,2,001,上市使用，现已退市,证实,LAA,封堵预防卒中可行,终点,:,可行性和安全性,对照,:,非随机化,入选,/,排除,:CHADS21,可耐受华法林治疗,终点,:,收集额外的安全性及有效性数据并汇总入,PROTECT AF,入选,/,排除,:,与,PROTECT AF,相同,终点,:,安全性及有效性,Safety and Efficacy,对照,:,华法林,入选,/,排除,:CHADS22,部分,CHADS2=1,术前未行氯吡格雷,7,日治疗,终点,:,安全性及有效性,对照,:,华法林,入选,/,排除,:CHADS2 1,可耐受华法林治疗,终点,:,有效性,对照,:,根据,CHADS2,评分预期的卒中比例,入选,/,排除,:,华法林不耐受或禁忌,终点,:,真实世界的额外信息,入选,/,排除,:,全部参加研究患者,ESC,指南,&,扩大指征,2002,2013,2004,2005,2006,2008,2009,2010,2011,2012,2015,2016,美国,WATCHMAN,左心耳封堵,3822,例,入选,/,排除,:2015,年,3,月到,2016,年,5,月美国所有患者,PREVAIL,研究,CAP,注册,研究,Pilot,研究,Post-FDA Approval,PROTECT AF,研究,ASAP,研究,EWOLUTIAON,注册,研究,超过,4,年长期术后随访,研究超过,8,000,名患者，随访超过,10,000,名患者,左心耳封堵,-,来自,Watchman,的证据,左心耳封堵,-,来自,Watchman,的证据,左心耳封堵,-,来自,ACP,的证据,ACP,回顾性单组多中心临床荟萃分析房颤卒中预防效果,患者数,1,047,参与中心,22,随访病人年,1,349,CHA,2,DS,2,-VASc(,平均,),4.5,HAS-BLED(,平均,),3.1,Age(,平均,),74.9,既往脑卒中,/TIA,37%,大出血史,47%,植入,ACP,时,OAC,服用率,29.5%,Source:,Tzikas,et al.(2014,May).,Multicenter experience with the Amplatzer Cardiac Plug(ACP),.Presented at EuroPCR 2014,Paris.Slides available at et al.(2014,May).,Multicenter experience with the Amplatzer Cardiac Plug(ACP),.Presented at EuroPCR 2014,Paris.Slides available at Patients,Total Patient Years,CHA,2,DS,2,-VASc,Score,1001,1349,4.43,Estimated Stroke Rate per CHA,2,DS,2,-VASc,Actual Annual Stroke Rate,(N strokes+TIA),5.62%,2.30%(31),-59%,Total Patients,Total Patient Years,HAS-BLED,Score,1001,1349,3.12,Estimated Bleeding Rate per HAS-BLED,Actual Annual Bleeding Rate,(N major bleeds),5.34%,2.08%(28),-61%,心房颤动,:,目前的认识和治疗建议,2015,中华心律失常学杂志,2015,年,10,月第,19,卷第,5,期,Chin J Cardiac Arrhyth,October 2015,Vol.19 No.5,2015,中国房颤指南中将左心耳封堵术列为,a,类适应症,对于,CHA2DS2-VASC,评分,2,的非瓣膜性房颤患者,如具下列情况之一，可行左心耳封堵术,:,不适合长期规范抗凝,治疗,长期规范抗凝治疗的基础上仍发生脑卒中或栓塞事件,;,HAS-BLED,评分,3,目前国内外左心耳封堵适应症,2016,年,2,月起，,美国医保,确认，符合如下条件的左心耳封堵装置植入属于医保支付范围：,患者的中风风险高，,CHADS-VASc,评分,3,患者应能接受短期华法林治疗，不能接受长期抗凝治疗。,患者与非介入医生充分沟通治疗方案选择。,美国医保,问题三：左心耳封堵的相关器械和选择？,左心耳的形态多样性给封堵带来的挑战,Cauliflower Windsock cactus chickenwing,WATCHMAN Device,Amplatzer Cardiac Plug,塞式封堵器,盘式封堵器,左心耳封堵器的种类,左心耳封堵器的种类,WATCHMAN,LAA Closure Device,PLAATO Device,AMPLATZER,Left Atrial Appendage Occluders,塞式封堵器,盘式封堵器,LARIAT,LAmbre,塞式封堵器,vs.,盘式封堵器：,表面积减少,51%,不压迫二尖瓣环及左上肺静脉,对房颤消融手术影响小,LUPV,ACP 16mm,盘式封堵器,Watchman,21mm,塞式封堵器,Kar S,et al.JACC:Interv 2014;7:801809,MV,MV,塞式封堵器与盘式封堵器的对比,-,动物模型,s.Kar Biology response following watchman and Amplatzer cardiac plug implantation in a canine left atrial appendage model.EUROPCR 2013,塞式封堵器贴壁情况,A,塞式封堵器头部内皮化情况,C,盘式封堵器封堵盘边缘贴合情况,B,盘式封堵器头部内皮化情况,D,塞式封堵器,盘式封堵器,塞式封堵器与盘式封堵器的对比,-,动物模型,单中心，前瞻性，随访,1,年,N=80,例,(40 WATCHMAN,40 ACP),全部,(n=80),WATCHMAN,(n=40),ACP(n=40),P,值,植入成功率,78/80(98%),38/40(95%),40/40(100%),0.49,残余漏,1000 patients,入组中心,:,欧洲、俄罗斯、中东地区的,47,个研究中心,入组时间,:,2013.10,2015.5,随访进程,:,在治疗中心采用标准随访流程,术后,13,个月常规随访,一年随访共进行两次,Ewolution,随访一年患者进程,Watchman,植入例数,:,N=1020,试验人群,:,N=1025,Watchman,植入成功例数,:,N=1005,筛选后发现解剖形态不适合,:N=5,一年后随访病人,:N=893/1005(89%),病人接受食道超声,:,N=875/1005(87%),具有,11,个月以上随访时间的患者百分比,:804/893(91%),一年内终止研究对象：,(N=112),减少人数,:N=91,退出随访,:,N=8,失访患者,:N=13,Ewolution,患者基线情况,病人基线数据,百分比,充血性心力衰竭,34%,高血压（不可控制或长期）,86%,年龄,80 years,26%,糖尿病,29%,缺血性,/,出血性卒中,20%/,1,5%,血管疾病,42%,女性,40%,肝肾功能异常,16%/4%,出血史或出血倾向,39%,CHA,2,DS,2,-VASc score 5,49%,HAS-BLED 3,40%,口服抗凝药禁忌,(N)OAC*,73%,Ewolution,术者信息统计,术者经验,#,术者人数,%,#,例数,%,2,年,14,22%,260,25%,合计,64,1020,术者经验方面，本试验入组的,78%,的术者手术经验低于两年，他们完成了,Ewolution,中四分之三的病例，然而这些初中级术者确丝毫没有影响该试验获得令人满意的临床结果。,Ewolution7,天术后并发症,Protect AF,CAP,Prevail,Ewolution,和所有先前的,Watchman,研究相比，,Ewolution,的,7,天手术,/,装置相关的并发症是最低的。,Ewolution,植入成功率及残余分流情况,Ewolution,植入装置成功率达到,98.5%,，植入即刻完全封堵率达到,99.8%,，首次随访完全封堵率达到,99.0%,。,Ewolution,年中风事件发生率,RR 84%,RR 85%,*,Effectiveness in stroke reduction vs.estimated in the absence of therapy for comparable CHA,2,DS,2,-VASc scores,based on Friberg et al.EHJ 2012,由于,Ewolution,试验入组了大量高出血风险、口服抗凝药禁忌的患者，试验设计初期，一年后的预期卒中发生率和出血发生率还是相当高的，然而一年随访数据却显著低于当初的预期。,Ewolution,随访一年的器械表面血栓及生存率,TEE,及临床随访发现，术后器械表面血栓发生率,3.7%,，其中仅有一例器械表面血栓引发卒中,一年,随访,数据显著,低于当初的预期,，证明了左心耳封堵术的,安全性和有效性。,Ewolution,年出血事件发生率,RR 48%,RR 54%,一年期的缺血性卒中发生率仅为,1.1%,对比预期下降了,84%,；一年期的出血发生率,2.3%,，对比预期降低了,54%,。,前瞻性、非随机、多中心研究,15,个中心,Germany,Spain,UK,Ireland and Czech Republic,204,位患者,随访,6,个月,(1214 patient follow-up months),严格执行高数据质量和高数据完整性,:,100%,的数据监测,独立委员会判断全部不良事件,ACP,上市后研究,Source:,Walsh,K.(2012,May).,Left atrial appendage closure with the AMPLATZER cardiac plug:results of the European post-market observational study.,Presented at EuroPCR 2012,Paris.,手术成功率,96.6%(197/204),首次器械植入成功率：,89.2%,封堵成功率,即刻,:99.5%,6,个月,:98.9%,大于,5 mm,残余分流：,0%,*Closure rate defined as absence of flow or flow 3 mm jet into the LAA,Source:,Walsh,K.(2012,May).,Left atrial appendage closure with the AMPLATZER cardiac plug:results of the European post-market observational study.,Presented at EuroPCR 2012,Paris.,ACP,上市后研究,N=204,*The stroke/TIA is reference to device-or procedure-related strokes as adjudicated by the AE Review Committee.,7 Days Post Procedure,7 days Post Procedure,Total,Periprocedural Stroke/TIA*,0(0.0%),0(0.0%),0(0.0%),Serious Pericardial Effusion,3(1.5%),0(0.0%),3(1.5%),Device Embolization,3(1.5%),0(0.0%),3(1.5%),Device-related Thrombus,0(0.0%),5(2.4%),5(2.4%),Total Safety Events,6(2.9%),5(2.4%),11(5.4%),Source:,Walsh,K.(2012,May).,Left atrial appendage closure with the AMPLATZER cardiac plug:results of the European post-market observational study.,Presented at EuroPCR 2012,Paris.,ACP,上市后研究,受试者预期年卒中发生率：,5.6,%,受试者实际卒中发生率：,1.98%,卒中发生率下降,65,%,Total Patients,Total Patient,Years,CHADS,2,Score,Estimated Stroke Rate,per CHADS,2,Actual Annual Stroke Rate(Number,of Events),ACP EU Observational,204,101,2.6,5.6%*,1.98%,(N=2),Source:,Walsh,K.(2012,May).,Left atrial appendage closure with the AMPLATZER cardiac plug:results of the European post-market observational study.,Presented at EuroPCR 2012,Paris.,ACP,上市后研究,我们的期待：,1,、更多的左心耳封堵的“真实世界”研究结果，指引封堵器类型选择、“露肩程度”选择、术后抗凝方案；,2,、更多的产品上市，增加选择性、降低治疗费用。,其它左心耳封堵装置,LARIAT,Device(SentreHEART),WaveCrest Device,(Coherex),3,LAmbre Device,(Lifetech),5,Image,Mechanism of Action,Epicardial,suture used to percutaneously ligate the LAA,PTFE covered frame,with retractable anchors,in the LAA,Nitinol disc covers,the exterior LAA.Anchors covered in polyester,Status,CE Mark;,FDA,510(k),Clearance,CE Mark,CE Mark,expected 2015,Clinical Data,Initial 89 patients reported in JACC in 2012,.,1,Multicenter study(n=154)published in JACC in 2014.,2,WAVECREST,I Trial of 73 patients presented at EuroPCR 2014.,4,FIM data,(n=39)reported at EuroPCR 2014.,6,CE Mark trial(n=150)completed but not yet reported,Bartus,K.,Han,F.T.,Bednarek,J.,Myc,J.,Kapelak,B.,Sadowski,J,.,Lee,R.J.(2013).Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation.,Journal,of the American College of Cardiology,62,108-118.,Price,M.J.,Gibson,D.N.,Yakubov,S.J.,Schultz,J.C.,Di Biase,L.,Natale,A,.,Valderrbano,M.(2014).Early safety and efficacy of percutaneous left atrial appendage suture ligation:results from the U.S.transcatheter LAA ligation consortium.,Journal of the American College of Cardiology,64,565-572.,Device,information accessed online at,Reddy,V.,et al.Accessed online at:,Y.Y.(2013).A new left atrial appendage occluder(Lifetech LAmbre Device)for stroke prevention in atrial fibrillation.,Cardiovascular Revascularization Medicine,14,134-136.,Lam,Y.Y.,et al.Accessed online at:,mm,者,预计生存期,1,年的病人；低卒中风险（,CHA,2,DS,2,-VASC,评分,0,或,1,分）或低出血风险（,HAS-BLED,评分,3,分）者；需华法林抗凝治疗的除房颤外其他疾病,者,存在卵圆孔未闭合并房间隔瘤和右向左分流，升主动脉,/,主动脉弓处存在复杂可移动,/,破裂,/,厚度,4mm,的动脉粥样硬化斑块,者,需要接受择期心外科手术者,39,谢谢各位专家！,