血栓抽吸在急性ST段抬高型心肌梗死中的研究进展

刘如晨　综述　徐争鸣　李田昌　审校

(中国人民解放军海军总医院心脏中心，北京100048)



血栓抽吸在急性ST段抬高型心肌梗死中的研究进展

刘如晨综述徐争鸣李田昌审校

(中国人民解放军海军总医院心脏中心，北京100048)

【摘要】冠状动脉粥样硬化斑块破裂及其所导致的血栓形成是急性ST段抬高型心肌梗死的病理生理学基础，及时有效的再灌注治疗是治疗的关键。经皮冠状动脉介入术是开通闭塞血管、改善患者预后的重要治疗手段，然而仍有1/3的患者在植入支架后心肌未得到有效的灌注，目前较公认的观点是血栓和斑块脱落引起微循环栓塞而导致无复流现象的发生，无复流的发生与患者的不良预后相关，增加心源性死亡、心力衰竭、恶性心律失常、住院期间死亡的发生率。血栓抽吸能够减少无复流的发生，但是对于患者临床预后的影响仍存在争议。现主要对血栓抽吸在急性ST段抬高型心肌梗死中的应用现状及进展进行综述。

【关键词】血栓；血栓抽吸；心肌再灌注；心肌梗死；无复流

1冠状动脉内血栓性质及其与预后的关系

冠状动脉粥样硬化斑块破裂及其所导致的血栓形成是急性心肌梗死的主要病理生理学基础[1]。冠状动脉内血栓的成分主要包括纤维蛋白、血小板、红细胞、白细胞、胆固醇结晶等成分。血栓的成分与缺血的时间相关，随着缺血时间的延长，血栓中的纤维蛋白成分增加，而血小板的成分减少[2]。不同部位产生的血栓的主要成分不同，左前降支内血栓含血小板成分多，而右冠状动脉内血栓的红细胞所占的比例高[3]。血栓的性质与远端栓塞、心肌灌注、左心功能、远期病死率相关。富含红细胞成分的血栓是远端栓塞的独立预测指标[4]，血栓中中性粒细胞比例高的患者心肌灌注差、心功能差[5]。而高血栓负荷、陈旧性血栓均是不良预后的独立预测指标[6-7]。理论上，在急诊经皮冠状动脉介入术(PCI)过程中应用血栓抽吸装置对冠状动脉内血栓进行抽吸，应该能够改善患者的临床预后。

2血栓负荷的评价

血栓负荷根据心肌梗死溶栓试验(thrombolysis in myocardial infarction，TIMI) 血栓分级可以分为5级[8]：0 级，无血栓；1 级，管腔显影模糊；2 级，血栓长度为血管直径的1/2 ；3 级，血栓长度为血管直径1/2～2 倍；4 级，血栓长度>2 倍血管直径；5 级，病变完全闭塞。上述分级存在缺陷，对于完全闭塞的病变，如果本身狭窄严重，血栓负荷不一定是最重的，因而对于完全闭塞的病变，有人将导丝通过后、球囊未扩张前再次造影评价血栓负荷[9]。

3血栓抽吸装置及其作用原理

目前临床上常用的血栓抽吸装置可以分为手动抽吸装置和机械抽吸装置，不同的血栓抽吸装置各有优缺点。手动抽吸装置是利用注射器手动抽吸产生负压从而将冠状动脉内的血栓抽出，如DIVER、EXPORT抽吸导管，人工抽吸装置价格便宜、操作简单、相对安全，同样也适用于老年患者[10]，但是存在抽吸力度小、抽吸效率不高的缺点[11]。常用的机械抽吸装置有X-Sizer和AngioJet。X-Sizer利用导管远端的螺旋形切割刀片将血栓切碎后真空抽吸将血栓移出体外[12]，X-Sizer存在冠状动脉穿孔的风险。AngioJet血栓装置则是利用导管尖端喷射的生理盐水将血栓击碎利用流变学原理将血栓移出。机械血栓抽吸导管较人工血栓抽吸导管在清除血栓方面更加彻底[13]，但是价格更贵。

4人工血栓抽吸的应用及最新进展

多项研究表明在急性心肌梗死介入治疗中应用人工血栓抽吸装置能够提高ST段的回落率，改善心肌灌注水平[14-16]。早期的临床研究和荟萃分析提示常规血栓抽吸能够改善患者的生存率[17-19]。2008年的TAPAS研究将1 071例急性ST段抬高型心肌梗死(STEMI)患者随机分为血栓抽吸组+PCI组和常规PCI组。随访30 d血栓抽吸组病死率降低，随访1 年心源性死亡及非致命性心肌梗死发生率血栓抽吸组均低于常规PCI组，该研究提示常规的血栓抽吸能够改善患者的远期预后[18]。来自Noman等[17]的研究支持血栓抽吸能够降低患者的病死率，但是当以缺血180 min作为亚组分析时发现，血栓抽吸仅能使缺血时间<180 min的患者获益。

随后开展的大量以病死率为临床终点的研究均未得出阳性结果[20-22]。2013年的TASTE 研究纳入7 244例STEMI 患者，随机分为血栓抽吸联合PCI组与单纯PCI组。随访30 d血栓抽吸组全因死亡率为2.8%，单纯PCI 组为3.0%，两组全因死亡率无统计学差异[23]。随访1年的结果也提示常规血栓抽吸并未减少全因死亡率、再发心肌梗死、支架内血栓的发生率[21]。TOTAL研究纳入10 732例STEMI患者，180 d的结果显示常规的血栓抽吸并未减少心源性死亡、支架内血栓、靶血管再次重建的发生，相反血栓抽吸组脑卒中的发生率高于未抽吸组[24]。最近公布随访1年的结果也提示常规血栓抽吸并未改善患者的长期预后并有可能增加脑卒中的风险[25]。

5机械血栓抽吸导管在临床的应用

机械血栓抽吸导管的抽吸效率高[26]，早期的研究提示机械血栓抽吸增加患者的病死率[27]，但在高血栓负荷的患者中能够减少再发心肌梗死和脑卒中的发生[28]。2004年纳入100例患者的随机对照研究中应用AngioJet装置进行抽吸,结果提示机械血栓抽吸组的ST段回落、TIMI帧数、心肌灌注显像、心肌梗死面积均优于未抽吸组[29]。两项大型的研究评价机械血栓抽吸在急性心肌梗死介入治疗中的应用得出的结果不一致。AIMI研究中纳入480例患者，应用第一代AngioJet血栓抽吸导管，显示使用机械血栓抽吸组心肌梗死的面积增加，主要不良心血管事件(major adverse cardiovascular events，MACE)的发生率更高[30]。而JETSTENT研究中纳入501例高血栓负荷(血栓积分≥3)的患者，结果显示机械血栓抽吸组ST段回落率更高，MACE事件发生率低[31]。目前尚缺乏大型的研究进一步评价机械血栓抽吸导管在急性心肌梗死介入治疗中的应用。

6血栓抽吸联合药物治疗

药物联合血栓抽吸能够改善心肌的灌注。INFUSE-AMI研究中，入选2009年11月～2011年12月间来源于6个国家37个中心的345例STEMI患者，入选标准为发病时间在4 h内且病变部位在前降支近段或中段的患者。将患者随机分为血栓抽吸+阿昔单抗组、血栓抽吸组、阿昔单抗组和对照组共4个组。利用心脏磁共振成像测量30 d后的左心室质量百分比。结果提示血栓抽吸联合冠状动脉内应用阿昔单抗能够减少心肌梗死面积[32]。然而随访1年的结果提示血栓抽吸联合冠状动脉内应用阿昔单抗能够显著减少心力衰竭的发生，但是对患者的病死率无影响[33]。同样，REOPEN-AMI研究评价血栓抽吸后冠状动脉内注射腺苷或硝普钠对微循环的影响，该研究共纳入240例TIMI血流在0/1级的患者，随机分为3个组，分别于血栓抽吸后冠状动脉内注射腺苷、硝普钠、生理盐水。结果显示血栓抽吸后冠状动脉内注射大量腺苷可以显著改善微循环，但是对MACE事件无影响[34]。

基于TASTE研究的结果及既往的试验研究结果，2014年欧洲血运重建指南将血栓抽吸在急性心肌梗死介入治疗中的使用作为Ⅱb A类推荐，不推荐在急性心肌梗死介入治疗中常规使用血栓抽吸装置[35]。临床中对血栓负荷较重的进行血栓抽吸，而非常规应用。在临床中对于究竟何种人群使用血栓抽吸、何时抽吸、选择何种血栓抽吸导管等值得进一步研究。

[ 参 考 文 献 ]

[1]Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi[J]. Br Heart J,1983,50(2):127-134.

[2]Mauri L, Cox D, Hermiller J, et al. The PROXIMAL trial: proximal protection during saphenous vein graft intervention using the Proxis Embolic Protection System:a randomized, prospective, multicenter clinical trial[J]. J Am Coll Cardiol,2007,50(15):1442-1449.

[3]Nagata Y, Usuda K, Uchiyama A, et al. Characteristics of the pathological images of coronary artery thrombi according to the infarct-related coronary artery in acute myocardial infarction[J]. Circ J, 2004,68(4):308-314.

[4]Yunoki K, Naruko T, Inoue T, et al. Relationship of thrombus characteristics to the incidence of angiographically visible distal embolization in patients with ST-segment elevation myocardial infarction treated with thrombus aspiration[J]. JACC Cardiovasc Interv,2013,6(4):377-385.

[5]Arakawa K, Yasuda S, Hao H, et al. Significant association between neutrophil aggregation in aspirated thrombus and myocardial damage in patients with ST-segment elevation acute myocardial infarction[J]. Circ J, 2009,73(1):139-144.

[6]Sianos G, Papafaklis MI, Daemen J, et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction:the importance of thrombus burden[J]. J Am Coll Cardiol, 2007,50(7):573-583.

[7]Kramer MC, van der Wal AC, Koch KT, et al. Presence of older thrombus is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention[J]. Circulation,2008,118(18):1810-1816.

[8]Gibson CM, de Lemos JA, Murphy SA, et al. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction:a TIMI 14 substudy[J]. Circulation, 2001,103(21):2550-2554.

[9]Sianos G, Papafaklis MI, Daemen J, et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction:the importance of thrombus burden[J]. J Am Coll Cardiol,2007,50(7):573-583.

[10]Valente S, Lazzeri C, Mattesini A, et al. Thrombus aspiration in elderly STEMI patients:a single center experience[J]. Int J Cardiol,2013,168(3):3097-3099.

[11]Bhindi R, Kajander OA, Jolly SS, et al. Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction:the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial[J]. Eur Heart J, 2015,36(29):1892-1900.

[12]Constantinides S, Lo TS, Been M, et al. Early experience with a helical coronary thrombectomy device in patients with acute coronary thrombosis[J]. Heart,2002,87(5):455-460.

[13]Parodi G, Valenti R, Migliorini A, et al. Comparison of manual thrombus aspiration with rheolytic thrombectomy in acute myocardial infarction[J]. Circ Cardiovasc Interv,2013,6(3):224-230.

[14]Burzotta F, Trani C, Romagnoli E, et al. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial[J]. J Am Coll Cardiol,2005,46(2):371-376.

[15]Silva-Orrego P, Colombo P, Bigi R, et al. Thrombus aspiration before primary angioplasty improves myocardial reperfusion in acute myocardial infarction:the DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) study[J]. J Am Coll Cardiol,2006,48(8):1552-1559.

[16]Burzotta F, Trani C, Romagnoli E, et al. Manual thrombus-aspiration improves myocardial reperfusion[J]. J Am Coll Cardiol,2005,46(2):371-376.

[17]Noman A, Egred M, Bagnall A, et al. Impact of thrombus aspiration during primary percutaneous coronary intervention on mortality in ST-segment elevation myocardial infarction[J]. Eur Heart J, 2012,33(24):3054-3061.

[18]Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS):a 1-year follow-up study[J]. Lancet,2008,371(9628):1915-1920.

[19]Burzotta F, de Vita M, Gu YL, et al. Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials[J]. Eur Heart J,2009,30(18):2193-2203.

[20]Jones DA, Rathod KS, Gallagher S, et al. Manual thrombus aspiration is not associated with reduced mortality in patients treated with primary percutaneous coronary intervention: an observational study of 10,929 patients with ST-segment elevation myocardial infarction from the London Heart Attack Group[J]. JACC Cardiovasc Interv,2015,8(4):575-584.

[21]Lagerqvist B, Frobert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction[J]. N Engl J Med, 2014,371(12):1111-1120.

[22]Watanabe H, Shiomi H, Nakatsuma K, et al. Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention[J]. J Am Heart Assoc,2015,4(6):e1962.

[23]Frobert O,Lagerqvist B,Olivecrona GK,et al.Thrombus aspiration during ST-segment elevation myocardial infarction[J]. N Engl J Med,2013,369(17):1587-1597.

[24]Jolly SS,Cairns JA,Yusuf S,et al.Randomized trial of primary PCI with or without routine manual thrombectomy[J]. N Engl J Med,2015,372(15):1389-1398.

[25]Jolly SS,Cairns JA,Yusuf S,et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction:1-year follow-up of the prospective randomised TOTAL trial[J]. Lancet, 2016,387(10014):127-135.

[26]Parodi G, Valenti R, Migliorini A, et al. Comparison of manual thrombus aspiration with rheolytic thrombectomy in acute myocardial infarction[J]. Circ Cardiovasc Interv,2013,6(3):224-230.

[27]Bavry AA, Kumbhani DJ, Bhatt DL. Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction:a comprehensive meta-analysis of randomized trials[J]. Eur Heart J, 2008,29(24):2989-3001.

[28]Navarese EP, Tarantini G, Musumeci G, et al. Manual vs mechanical thrombectomy during PCI for STEMI: a comprehensive direct and adjusted indirect meta-analysis of randomized trials[J]. Am J Cardiovasc Dis, 2013,3(3):146-157.

[29]Antoniucci D, Valenti R, Migliorini A, et al. Comparison of rheolytic thrombectomy before direct infarct artery stenting versus direct stenting alone in patients undergoing percutaneous coronary intervention for acute myocardial infarction[J]. Am J Cardiol,2004,93(8):1033-1035.

[30]Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction:30-day results from a multicenter randomized study[J]. J Am Coll Cardiol,2006,48(2):244-252.

[31]Migliorini A,Stabile A,Rodriguez AE,et al. Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction.The JETSTENT trial[J]. J Am Coll Cardiol,2010,56(16):1298-1306.

[32]Stone GW,Maehara A,Witzenbichler B,et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction:the INFUSE-AMI randomized trial[J]. JAMA, 2012,307(17):1817-1826.

[33]Stone GW,Witzenbichler B,Godlewski J,et al. Intralesional abciximab and thrombus aspiration in patients with large anterior myocardial infarction:one-year results from the INFUSE-AMI trial[J]. Circ Cardiovasc Interv,2013,6(5):527-534.

[34]Niccoli G,Rigattieri S,de Vita MR,et al.Open-label,randomized,placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction:the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction)[J]. JACC Cardiovasc Interv,2013,6(6):580-589.

[35]Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology(ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions(EAPCI)[J].Eur Heart J, 2014,35(37):2541-2619.

基金项目：海军后勤科研项目(CHJ12L020)

作者简介：刘如晨(1989—)，在读硕士，主要从事急性冠状动脉综合征研究。Email: 444532541@qq.com 通信作者：李田昌(1963—)，主任医师，博士，主要从事冠心病研究。Email: ltc909@aliyun.com

【中图分类号】R542.2

【文献标志码】A【DOI】10.16806/j.cnki.issn.1004-3934.2016.03.006

收稿日期：2015-10-21

Thrombus Aspiration in the Treatment of Acute ST-segment Elevation Myocardial Infarction

LIU Ruchen,XU Zhengming,LI Tianchang

【Abstract】ST-segment elevation myocardial infarction is characteried by plaque rupture and occlusion of the infarct artery with thrombus. Reperfusion of myocardial tissue is the main goal of primary percutaneous coronary intervention(PPCI) with stent implantation in the treatment of acute ST-segment elevation myocardial infarction. Although PPCI has contributed to a dramatic reduction in cardiovascular mortality, normal myocardial perfusion is not restored in approximately one-third of these patients. Several mechanisms may contribute to myocardial reperfusion failure, in particular distal embolization of the thrombus and plaque fragments failure. No-reflow is associated with poor prognosis in patients with increased cardiac death, heart failure, malignant arrhythmia death during hospitalization. Aspiration thrombectomy during PPCI has been proposed to prevent embolization in order to improve these outcomes. Even though numerous international studies haven, there are conflicting results on the clinical impact of aspiration thrombectomy during PPCI. In particular, the data on long-term clinical outcomes are still inconsistent. In this review,we have carefully analyzed literature data on thrombectomy during PPCI, taking into account the most recent studies.

【Key words】Thrombus; Thrombectomy; Myocardial reperfusion; Myocardial infarction; No-reflow