左心耳封堵術(shù)應(yīng)用進(jìn)展PPT精選文檔

1、左心耳封堵術(shù)應(yīng)用進(jìn)展韓寶石韓寶石解放軍總醫(yī)院心血管內(nèi)科解放軍總醫(yī)院心血管內(nèi)科20172017年年6 6月月1房顫與腦卒中3300萬房顫患者 90%NVAF患者的血栓來源于左心耳45%未正規(guī)服用華法林抗凝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 o

2、f 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;30:5285362節(jié)律或心率節(jié)律或心率起搏器起搏器藥物藥物控制控制卒中或栓塞卒中或栓塞華法林華法林左心耳左心耳結(jié)扎結(jié)扎封堵封堵消融消融新型口服抗凝藥新型口服抗凝藥達(dá)比加達(dá)比加群群利利伐沙班伐沙班阿阿哌沙班哌沙班房顫治療房顫治療房顫治療策

3、略3問題一：傳統(tǒng)或新型口服抗凝藥物，預(yù)防房顫患者卒中的“真實(shí)世界”情況？4Piccini, et al. Pharmacotherapy in Medicare beneficiaries with atrial fibrillation. Heart Rhythm. 2012;9:1403-1408據(jù)統(tǒng)計(jì)，高危患者人群華法林應(yīng)用率不足60% 。0%20%40%60%80%100%123456不同不同CHADS2評(píng)分華法林使用情況評(píng)分華法林使用情況CHADS2 評(píng)分評(píng)分(n=27,164)房顫患者華法林使用率華法林5-5-4-3-2-1INR過度抗凝抗凝不足治療劑量44% 出血病人INR超過3

4、.048% 血栓栓塞病人INR小于2.0 1現(xiàn)狀： 許多患者INR控制不佳，多數(shù)時(shí)間不在治療劑量。 在美國(guó)，華法林是老年人因藥物副作用而急診住院最常見的藥物2。華法林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 61 Glazer NL, Arch Intern Med (2007)2 Shen AY, J Am Coll Cardiol (2007)3 Go AS, JAMA (2

5、003) 華法林控制INR要求很高，需要評(píng)估權(quán)衡卒中和出血風(fēng)險(xiǎn)。 只有約50%服用華法林的患者達(dá)到了治療劑量的抗凝強(qiáng)度。不在治療劑量的患者會(huì)面臨高的出血不在治療劑量的患者會(huì)面臨高的出血/ /缺缺血性卒中風(fēng)險(xiǎn)血性卒中風(fēng)險(xiǎn)華法林7新型口服抗凝藥達(dá)比加群達(dá)比加群 1利伐沙班利伐沙班 2阿哌沙班阿哌沙班 3對(duì)照組華法林華法林華法林總?cè)脒x病例數(shù)18,11314,26418,201隨訪時(shí)間2 年1.94 年1.8 年平均CHADS2評(píng)分結(jié)果 (首要終點(diǎn)為卒中或系統(tǒng)栓塞)較華法林降低較華法林降低較華法林降低1 Connelly SJ et al, NEJM 2009; 361:1139-5

6、1 2 Patel MR et al, NEJM 2012; 365:883-913 Granger, J MD. NEJM 2012;365:981-928治療藥物治療藥物藥物治療中斷率藥物治療中斷率年大出血率年大出血率利伐沙班124%3.6%阿哌沙班225%2.1%達(dá)比加群3 (150 mg)21%3.3%依度沙班4(60 mg / 30 mg)33 % / 34% 2.8% / 1.6%華法林1-417 28%3.1 3.6%新型口服抗凝藥1Connolly, S. NEJM 2009; 361:1139-1151 2 yrs follow-up (Corrected) 2Patel,

7、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.出血風(fēng)險(xiǎn)、抗凝效果仍不能令人滿意出血風(fēng)險(xiǎn)、抗凝效果仍不能令人滿意9問題二：房顫患者抗凝治療的問題，是否有替代辦法或解決方案？10作者作者病人數(shù)病人數(shù)隨訪時(shí)間隨訪時(shí)間人群預(yù)估卒中人群預(yù)估卒中發(fā)生率發(fā)生率植入封堵器后實(shí)際卒中發(fā)生率Block1645 years6.6%3.

8、3%Park2732 years5.0%0.0%Ussia32040 10 months6.4%0.0%De Meester4103 47 months7.1%0.0%Ostermayer51119.8 months6.3%2.2%1.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 su

9、boptimal for warfarin therapy: 5-year results of the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) Study. JACC Cardiovascular Interventions, 2, 594-600.2.Park, J. W., Leithuser, B., Gerk, U., Vrsansky, M., & Jung, F. (2009) Percutaneous left atrial appendage transcatheter o

10、cclusion (PLAATO) for stroke prevention in AF: 2-year outcomes. Journal of Invasive Cardiology, 21, 446-50.3.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

11、events in high-risk patients with chronic atrial fibrillation. Catheter Cardiovascular Interventions, 74(2):217-22.4.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 Car

12、diology, 142, 195-196. 5.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 internati

13、onal multi-center feasibility trials. Journal of the American College of Cardiology, 46, 9-14.左心耳封堵-來自PLAATO的證據(jù)第一個(gè)LAA封堵裝置2001上市使用，現(xiàn)已退市證實(shí)LAA封堵預(yù)防卒中可行11終點(diǎn):可行性和安全性對(duì)照: 非隨機(jī)化入選/排除: CHADS21, 可耐受華法林治療終點(diǎn): 收集額外的安全性及有效性數(shù)據(jù)并匯總?cè)隤ROTECT AF入選/排除: 與PROTECT AF相同終點(diǎn): 安全性及有效性Safety and Efficacy對(duì)照: 華法林 入選/排除: CHADS22, 部分C

14、HADS2=1 術(shù)前未行氯吡格雷7日治療終點(diǎn): 安全性及有效性對(duì)照: 華法林入選/排除: CHADS2 1, 可耐受華法林治療終點(diǎn): 有效性對(duì)照: 根據(jù)CHADS2評(píng)分預(yù)期的卒中比例 入選/排除: 華法林不耐受或禁忌終點(diǎn): 真實(shí)世界的額外信息入選/排除: 全部參加研究患者ESC 指南指南 & 擴(kuò)大指征擴(kuò)大指征200220132004200520062008200920102011201220152016美國(guó)WATCHMAN左心耳封堵3822例例入選/排除: 2015年3月到2016年5月美國(guó)所有患者PREVAIL研究CAP注冊(cè)研究Pilot研究Post-FDA ApprovalPROT

15、ECT AF研究ASAP研究EWOLUTIAON注冊(cè)研究超過超過4年長(zhǎng)期術(shù)后隨訪年長(zhǎng)期術(shù)后隨訪研究超過研究超過8,000名患者，隨訪超過名患者，隨訪超過10,000名患者名患者左心耳封堵-來自WATCHMAN的證據(jù)12左心耳封堵-來自WATCHMAN的證據(jù)13左心耳封堵-來自ACP的證據(jù) ACP回顧性單組多中心臨床薈萃分析房顫卒中預(yù)防效果回顧性單組多中心臨床薈萃分析房顫卒中預(yù)防效果患者數(shù)患者數(shù)1,047參與中心參與中心22隨訪病人年隨訪病人年1,349CHA2DS2-VASc (平均平均)4.5HAS-BLED (平均平均)3.1Age (平均平均)74.9既往腦卒中既往腦卒中/ TIA37%

16、大出血史大出血史47%植入植入ACP時(shí)時(shí)OAC服用率服用率29.5%Source: Tzikas, et al. (2014, May). Multicenter experience with the Amplatzer Cardiac Plug (ACP). Presented at EuroPCR 2014, Paris. Slides available at http:/ 14左心耳封堵-來自ACP的證據(jù)Source: Tzikas, et al. (2014, May). Multicenter experience with the Amplatzer Cardiac Plug

17、(ACP). Presented at EuroPCR 2014, Paris. Slides available at http:/ 5.62%2.30%0%1%2%3%4%5%6%卒中下降率卒中下降率 vs. 研究人群預(yù)估值研究人群預(yù)估值Estimated based on CHA2DS2-VASc ScoreObserved rate in StudyTotal PatientsTotal Patient YearsCHA2DS2-VASc Score100113494.43Estimated Stroke Rate per CHA2DS2-VAScActual Annual Strok

18、e Rate (N strokes + TIA)5.62%2.30% (31)-59%5.34%2.08%0%1%2%3%4%5%6%出血下降率出血下降率 vs.研究人群預(yù)估值研究人群預(yù)估值Estimated based on HAS-BLED ScoreObserved rate in StudyTotal PatientsTotal Patient YearsHAS-BLED Score100113493.12Estimated Bleeding Rate per HAS-BLEDActual Annual Bleeding Rate (N major bleeds)5.34%2.08%

19、(28)-61%15心房顫動(dòng):目前的認(rèn)識(shí)和治療建議2015中華心律失常學(xué)雜志 2015 年 10 月第 19 卷第 5 期 Chin J Cardiac Arrhyth,October 2015,Vol.19 No.52015中國(guó)房顫指南中將左心耳封堵術(shù)列為a類適應(yīng)癥對(duì)于 CHA2DS2-VASC 評(píng)分2的非瓣膜性房顫患者,如具下列情況之一，可行左心耳封堵術(shù):不適合長(zhǎng)期規(guī)范抗凝治療長(zhǎng)期規(guī)范抗凝治療的基礎(chǔ)上仍發(fā)生腦卒中或栓塞事件; HAS-BLED 評(píng)分3目前國(guó)內(nèi)外左心耳封堵適應(yīng)癥2016年2月起，美國(guó)醫(yī)保確認(rèn)，符合如下條件的左心耳封堵裝置植入屬于醫(yī)保支付范圍：患者的中風(fēng)風(fēng)險(xiǎn)高，CHADS-VA

20、Sc評(píng)分3患者應(yīng)能接受短期華法林治療，不能接受長(zhǎng)期抗凝治療。患者與非介入醫(yī)生充分溝通治療方案選擇。美國(guó)醫(yī)保16問題三：左心耳封堵的相關(guān)器械和選擇？17左心耳的形態(tài)多樣性給封堵帶來的挑戰(zhàn)Cauliflower Windsock cactus chickenwing18WATCHMAN DeviceAmplatzer Cardiac Plug塞式封堵器塞式封堵器盤式封堵器盤式封堵器左心耳封堵器的種類19左心耳封堵器的種類WATCHMAN LAA Closure Device PLAATO DeviceAMPLATZER Left Atrial Appendage Occluders塞式封堵器塞式封

21、堵器盤式封堵器盤式封堵器LARIAT LAmbre20塞式封堵器vs.盤式封堵器：表面積減少51%不壓迫二尖瓣環(huán)及左上肺靜脈對(duì)房顫消融手術(shù)影響小LUPVACP 16mm 盤式封堵器Watchman 21mm 塞式封堵器Kar S, et al. JACC: Interv 2014;7:801809MVMV塞式封堵器與盤式封堵器的對(duì)比-動(dòng)物模型21S.KAR BIOLOGY RESPONSE FOLLOWING WATCHMAN AND AMPLATZER CARDIAC PLUG IMPLANTATION IN A CANINE LEFT ATRIAL APPENDAGE MODEL. EUR

22、OPCR 2013 塞式封堵器貼壁塞式封堵器貼壁情況情況A塞式塞式封堵器頭部?jī)?nèi)皮化封堵器頭部?jī)?nèi)皮化情況情況C盤式封堵器封堵盤邊緣貼合盤式封堵器封堵盤邊緣貼合情況情況B盤式封堵器頭部?jī)?nèi)皮化情況盤式封堵器頭部?jī)?nèi)皮化情況D塞式封堵器塞式封堵器盤式封堵器盤式封堵器塞式封堵器與盤式封堵器的對(duì)比-動(dòng)物模型22單中心，前瞻性，隨訪1年N = 80 例 (40 WATCHMAN, 40 ACP)全部全部(n = 80)WATCHMAN (n = 40)ACP (n = 40)P值值植入成功率植入成功率78/80 (98%)38/40 (95%)40/40 (100%)0.49殘余漏殘余漏 1000 patie

23、nts入組中心:歐洲、俄羅斯、中東地區(qū)的47個(gè)研究中心入組時(shí)間:2013.102015.5隨訪進(jìn)程:在治療中心采用標(biāo)準(zhǔn)隨訪流程術(shù)后13個(gè)月常規(guī)隨訪一年隨訪共進(jìn)行兩次25Ewolution隨訪一年患者進(jìn)程隨訪一年患者進(jìn)程Watchman 植入例數(shù)植入例數(shù): N = 1020試驗(yàn)人群試驗(yàn)人群: N = 1025Watchman植入成功例數(shù)植入成功例數(shù): N = 1005篩選后發(fā)現(xiàn)解剖形態(tài)不適合篩選后發(fā)現(xiàn)解剖形態(tài)不適合: N = 5一年后隨訪病人一年后隨訪病人: N = 893/1005 (89%)病人接受食道超聲病人接受食道超聲: N = 875/1005 (87%)具有具有11個(gè)月以上隨訪時(shí)間的

24、患者百分比個(gè)月以上隨訪時(shí)間的患者百分比: 804/893 (91%)一年內(nèi)終止研究對(duì)象：一年內(nèi)終止研究對(duì)象：(N = 112)減少人數(shù)減少人數(shù): N = 91退出隨訪退出隨訪: N = 8失訪患者失訪患者: N = 1326Ewolution患者基線情況患者基線情況病人基線數(shù)據(jù)百分比充血性心力衰竭34%高血壓（不可控制或長(zhǎng)期）86%年齡 80 years26%糖尿病29%缺血性/出血性卒中20% / 15%血管疾病42%女性40%肝腎功能異常16% / 4%出血史或出血傾向39%CHA2DS2-VASc score 549%HAS-BLED 340%口服抗凝藥禁忌 (N)OAC*73%27Ew

25、olution術(shù)者信息統(tǒng)計(jì)術(shù)者信息統(tǒng)計(jì)術(shù)者經(jīng)驗(yàn)術(shù)者經(jīng)驗(yàn)# 術(shù)者人數(shù)術(shù)者人數(shù)%# 例數(shù)例數(shù)%2年年1422%26025%合計(jì)合計(jì)641020術(shù)術(shù)者經(jīng)驗(yàn)方面，本試驗(yàn)入組的者經(jīng)驗(yàn)方面，本試驗(yàn)入組的78% 的術(shù)者手術(shù)經(jīng)驗(yàn)低于兩年，他們完的術(shù)者手術(shù)經(jīng)驗(yàn)低于兩年，他們完成了成了Ewolution中中四分之三的病例，然而這些初中級(jí)術(shù)者確絲毫沒有影四分之三的病例，然而這些初中級(jí)術(shù)者確絲毫沒有影響該試驗(yàn)獲得令人滿意的臨床結(jié)果。響該試驗(yàn)獲得令人滿意的臨床結(jié)果。28Ewolution7天術(shù)后并發(fā)癥天術(shù)后并發(fā)癥Protect AFCAPPrevailEwolution和所有先前的和所有先前的Watchman研究研究相

26、比，相比，Ewolution的的7天手術(shù)天手術(shù)/裝裝置相關(guān)的并發(fā)癥是最低的。置相關(guān)的并發(fā)癥是最低的。29Ewolution植入成功率及殘余分流情況植入成功率及殘余分流情況98.5%71.3%93.5%99.8%99.0%0%20%40%60%80%100%120%Implant SuccessFirst Device Release SuccessfulFirst Device Size correctComplete Seal or Jet Size 5 mm aComplete Seal or Jet Size 5 mm aEwolution植入裝置成功率達(dá)到98.5%， 植入即刻完全封堵

27、率達(dá)到99.8%，首次隨訪完全封堵率達(dá)到99.0%。30Ewolution年中風(fēng)事件發(fā)生率年中風(fēng)事件發(fā)生率7.2%10.1%1.1%1.5%0%2%4%6%8%10%12%Ischemic StrokeIschemic Stroke/TIA/SEExpected, based on CHA2DS2-VASc*Observed in EWOLUTIONRR 84%RR 85%*Effectiveness in stroke reduction vs. estimated in the absence of therapy for comparable CHA2DS2-VASc scores ba

28、sed on Friberg et al. EHJ 2012由于Ewolution試驗(yàn)入組了大量高出血風(fēng)險(xiǎn)、口服抗凝藥禁忌的患者，試驗(yàn)設(shè)計(jì)初期，一年后的預(yù)期卒中發(fā)生率和出血發(fā)生率還是相當(dāng)高的，然而一年隨訪數(shù)據(jù)卻顯著低于當(dāng)初的預(yù)期。31Ewolution隨訪一年的器械表面血栓及生存率隨訪一年的器械表面血栓及生存率 TEE及臨床隨訪發(fā)現(xiàn)，術(shù)后器械表面血栓發(fā)生率3.7%，其中僅有一例器械表面血栓引發(fā)卒中 一年隨訪數(shù)據(jù)顯著低于當(dāng)初的預(yù)期，證明了左心耳封堵術(shù)的安全性和有效性。32Ewolution年出血事件發(fā)生率年出血事件發(fā)生率5.0%5.0%2.6%2.3%0%1%2%3%4%5%6%MMExpect

29、ed, based on HAS-BLED*Observed in EWOLUTIONRR 48%RR 54%一年期的缺血性卒中發(fā)生率僅為1.1%,對(duì)比預(yù)期下降了84%；一年期的出血發(fā)生率2.3%，對(duì)比預(yù)期降低了54%。33前瞻性、非隨機(jī)、多中心研究, 15 個(gè)中心Germany, Spain, UK, Ireland and Czech Republic204 位患者 隨訪6個(gè)月 (1214 patient follow-up months)嚴(yán)格執(zhí)行高數(shù)據(jù)質(zhì)量和高數(shù)據(jù)完整性 :100% 的數(shù)據(jù)監(jiān)測(cè)獨(dú)立委員會(huì)判斷全部不良事件ACP上市后研究Source: Walsh, K. (2012, Ma

30、y). Left atrial appendage closure with the AMPLATZER cardiac plug: results of the European post-market observational study. Presented at EuroPCR 2012, Paris.手術(shù)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個(gè)月: 98.9% 大于5 mm殘余分流：0%* Closure rate defined as absence of flow or flow 3 mm jet into the

31、LAAResidual flow ( 3 mm)0.5%0.5%1.1%1.1%Closure99.5%99.5%98.9%98.9%ImplantDischarge1 Mo.6 Mo.80%82%84%86%88%90%92%94%96%98%100%Occlusion SuccessSource: Walsh, K. (2012, May). Left atrial appendage closure with the AMPLATZER cardiac plug: results of the European post-market observational study. Prese

32、nted 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 ProcedureTotalPeriprocedural Stroke/TIA*0 (0.0%)0 (0.0%)0 (0.0%)Serious Pericardial Effusion3 (1.5%)0 (0.0%)3

33、(1.5%)Device Embolization3 (1.5%)0 (0.0%)3 (1.5%)Device-related Thrombus0 (0.0%)5 (2.4%)5 (2.4%)Total Safety Events6 (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

34、 at EuroPCR 2012, Paris.ACP上市后研究受試者預(yù)期年卒中發(fā)生率：5.6%受試者實(shí)際卒中發(fā)生率： 1.98%卒中發(fā)生率下降卒中發(fā)生率下降65% Total PatientsTotal Patient YearsCHADS2 ScoreEstimated Stroke Rate per CHADS2Actual Annual Stroke Rate (Number of Events)ACP EU Observational2041012.65.6%*1.98% (N = 2)Source: Walsh, K. (2012, May). Left atrial append

35、age closure with the AMPLATZER cardiac plug: results of the European post-market observational study. Presented at EuroPCR 2012, Paris.ACP上市后研究我們的期待：1、更多的左心耳封堵的“真實(shí)世界”研究結(jié)果，指引封堵器類型選擇、“露肩程度”選擇、術(shù)后抗凝方案；2、更多的產(chǎn)品上市，增加選擇性、降低治療費(fèi)用。38其它左心耳封堵裝置LARIAT Device (SentreHEART)WaveCrest Device(Coherex)3LAmbre Device(Li

36、fetech)5ImageMechanism of ActionEpicardial suture used to percutaneously ligate the LAA PTFE covered frame, with retractable anchors in the LAANitinol disc covers the exterior LAA. Anchors covered in polyesterStatusCE Mark; FDA 510(k) ClearanceCE MarkCE Mark expected 2015Clinical DataInitial 89 patients reported in JACC in 2012.1 Multicenter study (n = 154) published in JACC in 2014.2WAVECREST I Trial of 73 patients presented