血栓抽吸在急性ST段抬高型心肌梗死中的研究進(jìn)展

劉如晨　綜述　徐爭(zhēng)鳴　李田昌　審校

(中國(guó)人民解放軍海軍總醫(yī)院心臟中心，北京100048)

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血栓抽吸在急性ST段抬高型心肌梗死中的研究進(jìn)展

劉如晨綜述徐爭(zhēng)鳴李田昌審校

(中國(guó)人民解放軍海軍總醫(yī)院心臟中心，北京100048)

【摘要】冠狀動(dòng)脈粥樣硬化斑塊破裂及其所導(dǎo)致的血栓形成是急性ST段抬高型心肌梗死的病理生理學(xué)基礎(chǔ)，及時(shí)有效的再灌注治療是治療的關(guān)鍵。經(jīng)皮冠狀動(dòng)脈介入術(shù)是開(kāi)通閉塞血管、改善患者預(yù)后的重要治療手段，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，目前較公認(rèn)的觀點(diǎn)是血栓和斑塊脫落引起微循環(huán)栓塞而導(dǎo)致無(wú)復(fù)流現(xiàn)象的發(fā)生，無(wú)復(fù)流的發(fā)生與患者的不良預(yù)后相關(guān)，增加心源性死亡、心力衰竭、惡性心律失常、住院期間死亡的發(fā)生率。血栓抽吸能夠減少無(wú)復(fù)流的發(fā)生，但是對(duì)于患者臨床預(yù)后的影響仍存在爭(zhēng)議?，F(xiàn)主要對(duì)血栓抽吸在急性ST段抬高型心肌梗死中的應(yīng)用現(xiàn)狀及進(jìn)展進(jìn)行綜述。

【關(guān)鍵詞】血栓；血栓抽吸；心肌再灌注；心肌梗死；無(wú)復(fù)流

1冠狀動(dòng)脈內(nèi)血栓性質(zhì)及其與預(yù)后的關(guān)系

冠狀動(dòng)脈粥樣硬化斑塊破裂及其所導(dǎo)致的血栓形成是急性心肌梗死的主要病理生理學(xué)基礎(chǔ)[1]。冠狀動(dòng)脈內(nèi)血栓的成分主要包括纖維蛋白、血小板、紅細(xì)胞、白細(xì)胞、膽固醇結(jié)晶等成分。血栓的成分與缺血的時(shí)間相關(guān)，隨著缺血時(shí)間的延長(zhǎng)，血栓中的纖維蛋白成分增加，而血小板的成分減少[2]。不同部位產(chǎn)生的血栓的主要成分不同，左前降支內(nèi)血栓含血小板成分多，而右冠狀動(dòng)脈內(nèi)血栓的紅細(xì)胞所占的比例高[3]。血栓的性質(zhì)與遠(yuǎn)端栓塞、心肌灌注、左心功能、遠(yuǎn)期病死率相關(guān)。富含紅細(xì)胞成分的血栓是遠(yuǎn)端栓塞的獨(dú)立預(yù)測(cè)指標(biāo)[4]，血栓中中性粒細(xì)胞比例高的患者心肌灌注差、心功能差[5]。而高血栓負(fù)荷、陳舊性血栓均是不良預(yù)后的獨(dú)立預(yù)測(cè)指標(biāo)[6-7]。理論上，在急診經(jīng)皮冠狀動(dòng)脈介入術(shù)(PCI)過(guò)程中應(yīng)用血栓抽吸裝置對(duì)冠狀動(dòng)脈內(nèi)血栓進(jìn)行抽吸，應(yīng)該能夠改善患者的臨床預(yù)后。

2血栓負(fù)荷的評(píng)價(jià)

血栓負(fù)荷根據(jù)心肌梗死溶栓試驗(yàn)(thrombolysis in myocardial infarction，TIMI) 血栓分級(jí)可以分為5級(jí)[8]：0 級(jí)，無(wú)血栓；1 級(jí)，管腔顯影模糊；2 級(jí)，血栓長(zhǎng)度為血管直徑的1/2 ；3 級(jí)，血栓長(zhǎng)度為血管直徑1/2～2 倍；4 級(jí)，血栓長(zhǎng)度>2 倍血管直徑；5 級(jí)，病變完全閉塞。上述分級(jí)存在缺陷，對(duì)于完全閉塞的病變，如果本身狹窄嚴(yán)重，血栓負(fù)荷不一定是最重的，因而對(duì)于完全閉塞的病變，有人將導(dǎo)絲通過(guò)后、球囊未擴(kuò)張前再次造影評(píng)價(jià)血栓負(fù)荷[9]。

3血栓抽吸裝置及其作用原理

目前臨床上常用的血栓抽吸裝置可以分為手動(dòng)抽吸裝置和機(jī)械抽吸裝置，不同的血栓抽吸裝置各有優(yōu)缺點(diǎn)。手動(dòng)抽吸裝置是利用注射器手動(dòng)抽吸產(chǎn)生負(fù)壓從而將冠狀動(dòng)脈內(nèi)的血栓抽出，如DIVER、EXPORT抽吸導(dǎo)管，人工抽吸裝置價(jià)格便宜、操作簡(jiǎn)單、相對(duì)安全，同樣也適用于老年患者[10]，但是存在抽吸力度小、抽吸效率不高的缺點(diǎn)[11]。常用的機(jī)械抽吸裝置有X-Sizer和AngioJet。X-Sizer利用導(dǎo)管遠(yuǎn)端的螺旋形切割刀片將血栓切碎后真空抽吸將血栓移出體外[12]，X-Sizer存在冠狀動(dòng)脈穿孔的風(fēng)險(xiǎn)。AngioJet血栓裝置則是利用導(dǎo)管尖端噴射的生理鹽水將血栓擊碎利用流變學(xué)原理將血栓移出。機(jī)械血栓抽吸導(dǎo)管較人工血栓抽吸導(dǎo)管在清除血栓方面更加徹底[13]，但是價(jià)格更貴。

4人工血栓抽吸的應(yīng)用及最新進(jìn)展

多項(xiàng)研究表明在急性心肌梗死介入治療中應(yīng)用人工血栓抽吸裝置能夠提高ST段的回落率，改善心肌灌注水平[14-16]。早期的臨床研究和薈萃分析提示常規(guī)血栓抽吸能夠改善患者的生存率[17-19]。2008年的TAPAS研究將1 071例急性ST段抬高型心肌梗死(STEMI)患者隨機(jī)分為血栓抽吸組+PCI組和常規(guī)PCI組。隨訪30 d血栓抽吸組病死率降低，隨訪1 年心源性死亡及非致命性心肌梗死發(fā)生率血栓抽吸組均低于常規(guī)PCI組，該研究提示常規(guī)的血栓抽吸能夠改善患者的遠(yuǎn)期預(yù)后[18]。來(lái)自Noman等[17]的研究支持血栓抽吸能夠降低患者的病死率，但是當(dāng)以缺血180 min作為亞組分析時(shí)發(fā)現(xiàn)，血栓抽吸僅能使缺血時(shí)間<180 min的患者獲益。

隨后開(kāi)展的大量以病死率為臨床終點(diǎn)的研究均未得出陽(yáng)性結(jié)果[20-22]。2013年的TASTE 研究納入7 244例STEMI 患者，隨機(jī)分為血栓抽吸聯(lián)合PCI組與單純PCI組。隨訪30 d血栓抽吸組全因死亡率為2.8%，單純PCI 組為3.0%，兩組全因死亡率無(wú)統(tǒng)計(jì)學(xué)差異[23]。隨訪1年的結(jié)果也提示常規(guī)血栓抽吸并未減少全因死亡率、再發(fā)心肌梗死、支架內(nèi)血栓的發(fā)生率[21]。TOTAL研究納入10 732例STEMI患者，180 d的結(jié)果顯示常規(guī)的血栓抽吸并未減少心源性死亡、支架內(nèi)血栓、靶血管再次重建的發(fā)生，相反血栓抽吸組腦卒中的發(fā)生率高于未抽吸組[24]。最近公布隨訪1年的結(jié)果也提示常規(guī)血栓抽吸并未改善患者的長(zhǎng)期預(yù)后并有可能增加腦卒中的風(fēng)險(xiǎn)[25]。

5機(jī)械血栓抽吸導(dǎo)管在臨床的應(yīng)用

機(jī)械血栓抽吸導(dǎo)管的抽吸效率高[26]，早期的研究提示機(jī)械血栓抽吸增加患者的病死率[27]，但在高血栓負(fù)荷的患者中能夠減少再發(fā)心肌梗死和腦卒中的發(fā)生[28]。2004年納入100例患者的隨機(jī)對(duì)照研究中應(yīng)用AngioJet裝置進(jìn)行抽吸,結(jié)果提示機(jī)械血栓抽吸組的ST段回落、TIMI幀數(shù)、心肌灌注顯像、心肌梗死面積均優(yōu)于未抽吸組[29]。兩項(xiàng)大型的研究評(píng)價(jià)機(jī)械血栓抽吸在急性心肌梗死介入治療中的應(yīng)用得出的結(jié)果不一致。AIMI研究中納入480例患者，應(yīng)用第一代AngioJet血栓抽吸導(dǎo)管，顯示使用機(jī)械血栓抽吸組心肌梗死的面積增加，主要不良心血管事件(major adverse cardiovascular events，MACE)的發(fā)生率更高[30]。而JETSTENT研究中納入501例高血栓負(fù)荷(血栓積分≥3)的患者，結(jié)果顯示機(jī)械血栓抽吸組ST段回落率更高，MACE事件發(fā)生率低[31]。目前尚缺乏大型的研究進(jìn)一步評(píng)價(jià)機(jī)械血栓抽吸導(dǎo)管在急性心肌梗死介入治療中的應(yīng)用。

6血栓抽吸聯(lián)合藥物治療

藥物聯(lián)合血栓抽吸能夠改善心肌的灌注。INFUSE-AMI研究中，入選2009年11月～2011年12月間來(lái)源于6個(gè)國(guó)家37個(gè)中心的345例STEMI患者，入選標(biāo)準(zhǔn)為發(fā)病時(shí)間在4 h內(nèi)且病變部位在前降支近段或中段的患者。將患者隨機(jī)分為血栓抽吸+阿昔單抗組、血栓抽吸組、阿昔單抗組和對(duì)照組共4個(gè)組。利用心臟磁共振成像測(cè)量30 d后的左心室質(zhì)量百分比。結(jié)果提示血栓抽吸聯(lián)合冠狀動(dòng)脈內(nèi)應(yīng)用阿昔單抗能夠減少心肌梗死面積[32]。然而隨訪1年的結(jié)果提示血栓抽吸聯(lián)合冠狀動(dòng)脈內(nèi)應(yīng)用阿昔單抗能夠顯著減少心力衰竭的發(fā)生，但是對(duì)患者的病死率無(wú)影響[33]。同樣，REOPEN-AMI研究評(píng)價(jià)血栓抽吸后冠狀動(dòng)脈內(nèi)注射腺苷或硝普鈉對(duì)微循環(huán)的影響，該研究共納入240例TIMI血流在0/1級(jí)的患者，隨機(jī)分為3個(gè)組，分別于血栓抽吸后冠狀動(dòng)脈內(nèi)注射腺苷、硝普鈉、生理鹽水。結(jié)果顯示血栓抽吸后冠狀動(dòng)脈內(nèi)注射大量腺苷可以顯著改善微循環(huán)，但是對(duì)MACE事件無(wú)影響[34]。

基于TASTE研究的結(jié)果及既往的試驗(yàn)研究結(jié)果，2014年歐洲血運(yùn)重建指南將血栓抽吸在急性心肌梗死介入治療中的使用作為Ⅱb A類(lèi)推薦，不推薦在急性心肌梗死介入治療中常規(guī)使用血栓抽吸裝置[35]。臨床中對(duì)血栓負(fù)荷較重的進(jìn)行血栓抽吸，而非常規(guī)應(yīng)用。在臨床中對(duì)于究竟何種人群使用血栓抽吸、何時(shí)抽吸、選擇何種血栓抽吸導(dǎo)管等值得進(jìn)一步研究。

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基金項(xiàng)目：海軍后勤科研項(xiàng)目(CHJ12L020)

作者簡(jiǎn)介：劉如晨(1989—)，在讀碩士，主要從事急性冠狀動(dòng)脈綜合征研究。Email: 444532541@qq.com 通信作者：李田昌(1963—)，主任醫(yī)師，博士，主要從事冠心病研究。Email: ltc909@aliyun.com

【中圖分類(lèi)號(hào)】R542.2

【文獻(xiàn)標(biāo)志碼】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