左心耳封堵术应用进展韩宝石

左心耳封堵术应用进展,韩宝石解放军总医院心血管内科2017年6月,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;61:755-7594 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% 。,CHADS2 评分,(n=27,164),房颤患者华法林使用率,华法林,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,1 Connelly SJ et al, NEJM 2009; 361:1139-51 2 Patel MR et al, NEJM 2012; 365:883-913 Granger, J MD. NEJM 2012;365:981-92,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？,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,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,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,Source: Tzikas, et al. (2014, May). Multicenter experience with the Amplatzer Cardiac Plug (ACP). Presented at EuroPCR 2014, Paris. Slides available at /Lectures/2014/Left-atrial-appendage-occlusion-for-stroke-prevention-in-atrial-fibrillation-multicentre-experience-with-the-Amplatzer-cardiac-plug,左心耳封堵-来自ACP的证据,Source: Tzikas, et al. (2014, May). Multicenter experience with the Amplatzer Cardiac Plug (ACP). Presented at EuroPCR 2014, Paris. Slides available at /Lectures/2014/Left-atrial-appendage-occlusion-for-stroke-prevention-in-atrial-fibrillation-multicentre-experience-with-the-Amplatzer-cardiac-plug,-59%,-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,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,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),Source: Chun, K. R., Bordignon, S., Urban, V., Perrotta, L., Dugo, D., Frnkranz, A., Schmidt, B. (2013). Left atrial appendage closure followed by six weeks antithrombotic therapy a prospective single center experience. Heart Rhythm, 10, 1792-1799.,塞式封堵器与盘式封堵器的对比-临床研究,问题四：左心耳封堵的“真实世界”研究结果？,Watchman真实世界的临床注册试验研究Ewolution,Ewolution随访一年患者进程,Ewolution患者基线情况,Ewolution术者信息统计,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,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,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 Republic204 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.,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%,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,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. trans