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穩(wěn)定性冠心病血運(yùn)重建策略進(jìn)展

2019-05-29 10:25沈迎張瑞巖沈衛(wèi)峰
心腦血管病防治 2019年2期
關(guān)鍵詞:記分生存率主干

沈迎 張瑞巖 沈衛(wèi)峰

2018年第9期《中華心血管病雜志》刊登了由中華醫(yī)學(xué)會(huì)心血管病分會(huì)介入心臟病學(xué)組和動(dòng)脈粥樣硬化與冠心病學(xué)組、中國(guó)醫(yī)師協(xié)會(huì)心血管內(nèi)科醫(yī)師分會(huì)血栓防治專業(yè)委員會(huì)制定的“穩(wěn)定性冠心病診斷與治療指南”(以下簡(jiǎn)稱新指南)[1]。新指南指出,穩(wěn)定性冠心病(stable coronary artery disease,SCAD)又稱為穩(wěn)定性冠狀動(dòng)脈綜合征,通常包括三種情況,即慢性勞累型心絞痛、缺血性心肌病、急性冠狀動(dòng)脈綜合征經(jīng)治療后疾病穩(wěn)定階段。新指南強(qiáng)調(diào)了臨床、無創(chuàng)性檢查(例如心電圖、核素心肌顯像、冠狀動(dòng)脈CTA)、負(fù)荷試驗(yàn)(運(yùn)動(dòng)或藥物激發(fā))以及冠狀動(dòng)脈造影在胸痛鑒別診斷中的價(jià)值;倡導(dǎo)依據(jù)臨床癥狀、左心室功能、負(fù)荷試驗(yàn)反應(yīng)和冠狀動(dòng)脈造影發(fā)現(xiàn),進(jìn)行綜合和動(dòng)態(tài)危險(xiǎn)評(píng)估,制定規(guī)范化治療;提出對(duì)強(qiáng)化藥物治療下仍有缺血癥狀及存在較大范圍心肌缺血證據(jù)的患者,根據(jù)臨床和冠狀動(dòng)脈病變特點(diǎn)選擇相應(yīng)的血運(yùn)重建策略,包括經(jīng)皮冠狀動(dòng)脈介入治療(PCI)或冠狀動(dòng)脈旁路移植術(shù)(CABG)。本文結(jié)合中國(guó)和歐美PCI指南[2,3],對(duì)新指南有關(guān)SCAD患者冠狀動(dòng)脈血運(yùn)重建策略作一解讀。

1?冠狀動(dòng)脈血運(yùn)重建的目的

SCAD患者冠狀動(dòng)脈血運(yùn)重建的主要目的是改善預(yù)后和緩解臨床癥狀[1~3]。以往的研究發(fā)現(xiàn),心肌缺血程度與心血管事件存在明顯的相關(guān)性。冠狀動(dòng)脈粥樣硬化所致管腔嚴(yán)重狹窄是引起心肌供氧(血)與需氧之間失平衡的主要原因,因此,對(duì)中重度心肌缺血患者(即使無心絞痛)應(yīng)考慮冠狀動(dòng)脈血運(yùn)重建。當(dāng)左主干狹窄>50%、左前降支近段狹窄>70%、二支或三支冠狀動(dòng)脈病變,且左心室功能受損(射血分?jǐn)?shù)<40%)時(shí),血運(yùn)重建能顯著改善患者的臨床預(yù)后[2,3]。心絞痛使患者的體力活動(dòng)和工作能力減低、反復(fù)住院、醫(yī)療費(fèi)用增加。遵循指南的內(nèi)科治療(包括抗心絞痛藥物)能降低死亡和心肌梗死風(fēng)險(xiǎn),改善癥狀,因此得到廣泛的推薦。對(duì)存在明顯冠狀動(dòng)脈病變和心絞痛癥狀且對(duì)藥物治療無反應(yīng)的患者行冠狀動(dòng)脈血運(yùn)重建,可明顯改善患者的生活質(zhì)量[4,5]。

2?冠狀動(dòng)脈病變解剖和功能學(xué)評(píng)估對(duì)血運(yùn)重建的作用

目前,冠狀動(dòng)脈內(nèi)影像學(xué)技術(shù)例如血管內(nèi)超聲(IVUS)和光學(xué)相干斷層顯像(OCT)主要用于評(píng)估斑塊形態(tài)、指導(dǎo)支架植入(例如擴(kuò)張程度、貼壁情況),以優(yōu)化PCI療效[6~8]。冠狀動(dòng)脈造影發(fā)現(xiàn),相當(dāng)一部分SCAD患者存在臨界病變(管腔內(nèi)徑狹窄40%~70%),但后者與心肌缺血癥狀之間的關(guān)系以及對(duì)預(yù)后的影響尚不清楚。因此,在冠狀動(dòng)脈造影時(shí)需要對(duì)這些臨界狹窄病變進(jìn)行功能學(xué)評(píng)估,其中血流儲(chǔ)備分?jǐn)?shù)(fractional flow reserve,F(xiàn)FR)測(cè)定是目前最常用的方法。在許多PCI預(yù)后研究中,F(xiàn)FR≤0.80常被視為冠狀動(dòng)脈血運(yùn)重建的最佳切點(diǎn)。與內(nèi)科藥物治療相比,F(xiàn)FR測(cè)定的應(yīng)用可改善SCAD患者PCI后生活質(zhì)量[9]。Zimmermann等[10]對(duì)三個(gè)隨機(jī)對(duì)照研究(FAME 2,DANAMI-3-PRIMULTI,COMPARE-ACUTE)的具體病人數(shù)據(jù)(Individual patient data)進(jìn)行薈萃分析,結(jié)果證明FFR指導(dǎo)的PCI能顯著降低死亡和心肌梗死發(fā)生率。最近,計(jì)算機(jī)冠狀動(dòng)脈定量血流比例(quantitive flow ratio,QFR)、瞬時(shí)無波形血流比值(iwFR),由于不需要注射腺苷和應(yīng)用壓力導(dǎo)絲,因此有望在評(píng)估冠狀動(dòng)脈病變功能學(xué)意義和指導(dǎo)PCI決策方面具有更好的應(yīng)用前景[11,12]。

3?冠狀動(dòng)脈血運(yùn)重建策略

堅(jiān)持“以病人為中心”的準(zhǔn)則,推薦應(yīng)用STS記分、EuroSCORE Ⅱ評(píng)估CABG后住院期死亡率,應(yīng)用Syntax記分評(píng)估冠狀動(dòng)脈解剖的復(fù)雜性以及PCI后遠(yuǎn)期死亡和并發(fā)癥風(fēng)險(xiǎn)[1,2,13]。同時(shí)強(qiáng)調(diào),對(duì)復(fù)雜高危冠狀動(dòng)脈病變且存在臨床合并癥患者由心臟團(tuán)隊(duì)和多學(xué)科團(tuán)隊(duì)做出血運(yùn)重建的決策[1,2]。

3.1?根據(jù)冠狀動(dòng)脈病變嚴(yán)重性:對(duì)合并左主干和(或)左前降支近段病變、多支血管病變患者,如何選擇CABG或PCI仍有爭(zhēng)議。近年來,新一代藥物洗脫支架的廣泛應(yīng)用顯著降低了PCI術(shù)后長(zhǎng)期不良事件發(fā)生率,進(jìn)一步拓寬了PCI在SCAD中的適應(yīng)證。

3.1.1?多支血管病變:新指南推薦,對(duì)多支血管病變患者,根據(jù)SYNTAX記分(歐洲心臟病學(xué)會(huì)提出的一種根據(jù)冠狀動(dòng)脈解剖特點(diǎn)進(jìn)行危險(xiǎn)分層的積分系統(tǒng))和SYNTAX Ⅱ記分來評(píng)估中、遠(yuǎn)期風(fēng)險(xiǎn),選擇合適的血運(yùn)重建策略[1~3]。三支血管病變(伴或不伴左前降支近端病變)或左前降支伴其他血管病變時(shí),CABG對(duì)改善生存率有益。對(duì)可能心臟性猝死伴懷疑心肌缺血誘發(fā)室性心律失常的患者,CABG或PCI均能改善生存率[4]。CABG對(duì)改善二支血管病變伴嚴(yán)重和廣泛心肌缺血患者的生存率有益,也能提高輕中度左心功能不全(射血分?jǐn)?shù)35%~50%)的多支血管病變患者或左前降支近端狹窄但心肌存活患者的生存率??傮w而言,SYNTAX記分<22分患者采用PCI與CABG后的心腦血管不良事件發(fā)生率相似,隨著冠狀動(dòng)脈病變程度增加(SYNTAX記分大),CABG的優(yōu)越性明顯提高。對(duì)三支血管病變且SYNTAX記分>22或累及左前降支的患者,更優(yōu)先考慮CABG。根據(jù)對(duì)100個(gè)臨床試驗(yàn)的93552例SCAD的薈萃分析發(fā)現(xiàn),與單純藥物治療相比,CABG降低20%全因死亡和21%心肌梗死[13]。使用新一代藥物洗脫支架的PCI也使死亡率降低,但CABG較PCI可減低再次血運(yùn)重建(尤其在PCI不能達(dá)到完全血運(yùn)重建時(shí))[14]。新指南建議,以冠狀動(dòng)脈病變直徑狹窄程度作為是否干預(yù)的決策依據(jù),病變直徑狹窄≥90%時(shí),可直接干預(yù);當(dāng)病變直徑狹窄<90%時(shí),建議僅對(duì)有缺血證據(jù)或FFR≤0.8的病變進(jìn)行干預(yù)。FAME系列研究證明,與單純根據(jù)冠狀動(dòng)脈造影相比,F(xiàn)FR指導(dǎo)冠狀動(dòng)脈多支病變血運(yùn)重建策略,其遠(yuǎn)期復(fù)合終點(diǎn)(包括死亡、心肌梗死或再次血運(yùn)重建)顯著降低。因此,F(xiàn)FR可能成為多支血管病變患者治療決策的參與指標(biāo)[15]。

3.1.2?左主干病變:對(duì)明顯左主干病變(狹窄>50%)患者,推薦用CABG以改善生存率。對(duì)某些選擇性無保護(hù)左主干患者可以用PCI替代CABG,包括解剖上PCI時(shí)并發(fā)癥低;遠(yuǎn)期療效好(例如SYNTAX記分<22分);開口或體部病變;臨床特征預(yù)示CABG風(fēng)險(xiǎn)高(例如STS預(yù)測(cè)死亡率>5%)。在對(duì)左主干病變患者行血運(yùn)重建決策時(shí),須考慮冠狀動(dòng)脈病變的嚴(yán)重性[16,17]。左主干病變伴遠(yuǎn)端血流低于TIMI(thrombolysis in myocardial infarction,一種描述急性心肌梗死冠脈內(nèi)溶栓后冠脈血流情況的評(píng)價(jià)指標(biāo))3級(jí)者,PCI較CABG更迅速和安全。對(duì)某些選擇性穩(wěn)定的無保護(hù)左主干病變患者,解剖上PCI低風(fēng)險(xiǎn),但預(yù)后上中等或重度不佳(例如SYNTAX記分<33分、左主干遠(yuǎn)端分叉病變),或者存在CABG高風(fēng)險(xiǎn)的臨床情況(例如中重度慢性阻塞性肺病、卒中或以往心臟手術(shù)史、STS積分預(yù)測(cè)手術(shù)死亡率>2%)的患者,PCI也是合理的。左主干病變、SYNTAX記分>33分、合并PCI的不利解剖因素的SCAD患者,優(yōu)先推薦CABG[1~3,13]。

3.1.3?以往接受過CABG:這些患者如發(fā)生靜脈橋血管病變(阻塞),為了控制心絞痛癥狀,應(yīng)盡量對(duì)自身(de novo)冠狀動(dòng)脈病變行PCI[18]。

3.1.4?慢性完全阻塞病變:在過去的10多年中,由于操作技術(shù)和介入器材(尤其是導(dǎo)絲)的發(fā)展,慢性完全阻塞病變PCI成功率有了很大的提高。盡管目前尚缺乏隨機(jī)對(duì)照研究的證據(jù),但對(duì)藥物治療后仍然存在心絞痛癥狀(伴或不伴無創(chuàng)性測(cè)定顯示高危表現(xiàn))的慢性完全阻塞病變患者,應(yīng)考慮介入治療[19,20]。PCI能改善慢性完全阻塞患者的左心功能、生活質(zhì)量和生存率,尤其當(dāng)存在較佳側(cè)支循環(huán)供血時(shí)[21,22]。

3.2?雜交手術(shù):對(duì)某些患者(例如高危左主干病變、左前降支明顯扭曲、慢性完全阻塞不宜PCI時(shí)),冠狀動(dòng)脈雜交手術(shù)無疑是一種較理想的選擇。冠狀動(dòng)脈雜交手術(shù)包括小切口將內(nèi)乳動(dòng)脈與左前降支“搭橋”,回旋支或右冠狀動(dòng)脈病變行支架術(shù)。冠狀動(dòng)脈雜交手術(shù)可能作為多支血管病變另一治療選擇,以提高療效-風(fēng)險(xiǎn)比[23]。

4?特殊臨床情況時(shí)血運(yùn)重建選擇

4.1?糖尿病:以往的研究指出,約20%~30%需要血運(yùn)重建的患者合并有糖尿病。后者使全身性動(dòng)脈粥樣硬化加速、動(dòng)脈內(nèi)皮功能異常,導(dǎo)致彌漫性冠狀動(dòng)脈和外周血管病變。糖尿病也增加血運(yùn)重建術(shù)后冠狀動(dòng)脈病變發(fā)展和支架內(nèi)再狹窄發(fā)生。薈萃分析顯示,在低或中等SYNTAX記分(0~32分)患者,PCI與CABG的心腦血管事件風(fēng)險(xiǎn)相似。但SYNTAX記分>32分患者,PCI的心腦血管事件風(fēng)險(xiǎn)增高[13,24]。糖尿病多支血管病變患者,尤其在適合左內(nèi)乳動(dòng)脈行前降支搭橋時(shí),應(yīng)優(yōu)先考慮CABG或雜交手術(shù)[25,26]。

4.2?慢性腎?。洪L(zhǎng)期腎功能減退患者常伴有嚴(yán)重冠狀動(dòng)脈粥樣硬化。大規(guī)模注冊(cè)研究表明,SCAD伴慢性腎病患者血運(yùn)重建對(duì)死亡率減低有益,且CABG較PCI獲益更大,但外科手術(shù)風(fēng)險(xiǎn)增大[27]。目前,介入操作技術(shù)進(jìn)步、術(shù)前充分準(zhǔn)備,使許多慢性腎病患者可以安全行PCI[28]。

4.3?瓣膜性心臟?。汗谛牟『喜⒅鲃?dòng)脈瓣狹窄患者,CABG和瓣膜置換聯(lián)合手術(shù)的圍術(shù)期風(fēng)險(xiǎn)較單純瓣膜手術(shù)明顯增大,但遠(yuǎn)期生存率較高。不能耐受外科手術(shù)或手術(shù)風(fēng)險(xiǎn)極高的主動(dòng)脈瓣狹窄患者,可考慮行經(jīng)皮主動(dòng)脈瓣植入術(shù)(transcatheter aortic valve implantation,TAVI)[29]。觀察性研究表明,TAVI術(shù)前或術(shù)中行PCI是安全、可行的[30]。缺血性二尖瓣反流患者CABG加二尖瓣修補(bǔ)術(shù)與單純CABG相比,減低反流嚴(yán)重性和左心室重構(gòu),但對(duì)遠(yuǎn)期臨床心功能和生存率無明顯改善作用[31]。

4.4?需要長(zhǎng)期口服抗凝劑:心房顫動(dòng)、靜脈血栓栓塞性疾病或接受瓣膜置換患者,需要長(zhǎng)期口服華法令或其他新型抗凝藥物[32]。對(duì)這些患者PCI時(shí)選用新一代藥物洗脫支架,以減少出血并發(fā)癥[2,3]。

5?血運(yùn)重建后抗栓治療

抗血小板治療是SCAD伴或不伴冠狀動(dòng)脈血運(yùn)重建患者二級(jí)預(yù)防的重要措施。雙聯(lián)抗血小板治療對(duì)預(yù)防冠心病患者血栓性并發(fā)癥和PCI后支架內(nèi)血栓形成至關(guān)重要,但須注意出血并發(fā)癥。后者與抗栓的療程和強(qiáng)度相關(guān)。中國(guó)和歐洲PCI指南推薦,SCAD患者植入新一代藥物洗脫支架后需雙聯(lián)抗血小板治療6個(gè)月[2,3],而美國(guó)指南則推薦12個(gè)月[33]。臨床上,對(duì)某些特殊人群(例如心房顫動(dòng)或以往接受人工瓣膜置入SCAD患者)在藥物洗脫支架術(shù)后需要三聯(lián)抗栓治療,旨在進(jìn)一步降低缺血事件。三聯(lián)抗栓包括阿司匹林+氯吡格雷(不用替格瑞洛)+一種口服抗凝劑。同時(shí),需對(duì)這些患者作進(jìn)一步精確的缺血和出血的風(fēng)險(xiǎn)分層,采取個(gè)體化治療。此外,除普遍采用預(yù)防性質(zhì)子泵抑制劑外,還應(yīng)考慮引起反復(fù)發(fā)作血栓形成的血管造影因素(例如支架直徑和長(zhǎng)度、支架膨脹不全、血運(yùn)重建完全性)以及血循環(huán)生物標(biāo)志物等,以期獲得聯(lián)合抗栓藥物治療的最大益處[34~37]。我國(guó)和歐美心肌血運(yùn)重建指南推薦,對(duì)需要抗凝治療的患者,PCI后短期內(nèi)(1~3個(gè)月)應(yīng)用三聯(lián)抗栓治療后,改用一種抗凝劑(例如華法令或新型口服抗凝藥)加氯吡格雷[2,3,33]。最近的研究指出,CABG后應(yīng)用雙聯(lián)抗血小板治療(阿司匹林+P2Y12抑制劑替格瑞洛)降低一年靜脈橋血管閉塞發(fā)生率[38]??傊?,最新發(fā)布的我國(guó)SCAD診治指南提出對(duì)這些患者的血運(yùn)重建策略(PCI和CABG)的規(guī)范,原則上,心肌缺血癥狀明顯或存在大塊瀕危心肌的冠心病患者,血運(yùn)重建的獲益最大。新一代藥物洗脫支架的應(yīng)用和全動(dòng)脈化外科血運(yùn)重建使臨床療效顯著改善。不管實(shí)施何種血運(yùn)重建策略,內(nèi)科藥物治療(尤其是抗血小板和抗凝治療)仍是改善SCAD患者心血管預(yù)后的基礎(chǔ)。對(duì)于某一個(gè)體患者而言,血運(yùn)重建方法的選擇主要基于對(duì)患者具體臨床風(fēng)險(xiǎn)評(píng)估、冠狀動(dòng)脈解剖和功能學(xué)測(cè)定,綜合多學(xué)科的作用,同時(shí)還應(yīng)考慮介入或外科醫(yī)生的技能和患者的意愿等,這些對(duì)優(yōu)化血運(yùn)重建策略極為重要。

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(收稿日期:2019-2-18)

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