王 建 王 焱
重度主動(dòng)脈瓣狹窄伴左室功能不全患者的臨床決策
王 建 王 焱
主動(dòng)脈瓣狹窄是發(fā)病率最高的心臟瓣膜病,其主要治療方法是外科主動(dòng)脈瓣置換術(shù)。當(dāng)患者出現(xiàn)左室擴(kuò)大、射血分?jǐn)?shù)降低及充血性心力衰竭時(shí),外科主動(dòng)脈瓣置換術(shù)的手術(shù)風(fēng)險(xiǎn)增大,造成了治療困難。經(jīng)導(dǎo)管主動(dòng)脈瓣置入術(shù)是一種侵入性更小的治療手段。該技術(shù)的發(fā)展為外科手術(shù)高危的重度主動(dòng)脈瓣狹窄患者的治療帶來了新希望。
重度主動(dòng)脈瓣狹窄;左室功能不全;外科主動(dòng)脈瓣置換;經(jīng)導(dǎo)管主動(dòng)脈瓣置入
鈣化性主動(dòng)脈瓣病變(calcific aortic valve disease,CAVD)是指非風(fēng)濕性原因引起的主動(dòng)脈瓣增厚和鈣化,根據(jù)是否存在左室流出道梗阻分為主動(dòng)脈瓣硬化和主動(dòng)脈瓣狹窄[1]。最近的研究表明,主動(dòng)脈瓣硬化和狹窄是CAVD的2個(gè)病理階段。在65歲以上的老年患者中,主動(dòng)脈瓣硬化約占25%,主動(dòng)脈瓣狹窄約占2%~5%[2-3]。重度主動(dòng)脈瓣狹窄已成為外科主動(dòng)脈瓣置換(surgical aortic valve replacement,SAVR)的主要指征。SAVR已被證實(shí)是重度主動(dòng)脈瓣狹窄確切有效的治療方法[4]。其中,高齡患者的手術(shù)死亡率(3%~5%)及遠(yuǎn)期的治療效果也是令人滿意的[5]。
高齡、合并癥多等因素使外科手術(shù)的死亡風(fēng)險(xiǎn)增加(5%~15%),且影響了患者術(shù)后的生存期。一項(xiàng)回顧性研究顯示,在有癥狀的重度主動(dòng)脈瓣狹窄患者中,行傳統(tǒng)SAVR的僅占35.2%,因手術(shù)風(fēng)險(xiǎn)過高接受經(jīng)導(dǎo)管主動(dòng)脈瓣置入(transcatheter aortic valve implantation,TAVI)或藥物治療的分別占5.6%和56.4%[5]。未行SAVR的重度主動(dòng)脈瓣狹窄患者中,2年的無心血管事件生存率僅有20%[6]。主動(dòng)脈瓣球囊成形(balloon aortic valvuloplasty,BAV)由于遠(yuǎn)期治療效果不佳,其應(yīng)用已經(jīng)越來越少,目前只作為術(shù)前緩解患者癥狀的過渡治療[7]。
重度主動(dòng)脈瓣狹窄的主要診斷依據(jù)是超聲心動(dòng)圖。典型表現(xiàn)為:瓣膜面積≤1.0 cm2(或主動(dòng)脈瓣面積系數(shù)≤0.6 cm2/m2),平均跨瓣壓差≥40 mmHg,主動(dòng)脈瓣流速≥4 m/s。然而,左室功能不全的患者前向血流減少,超聲心動(dòng)圖測(cè)得主動(dòng)脈瓣瓣口面積≤1.0 cm2,而跨瓣壓差或主動(dòng)脈瓣流速并不滿足上述標(biāo)準(zhǔn)。如果行負(fù)荷的超聲心電圖,心輸出量增加,瓣膜“真性”狹窄者,跨瓣壓增大、流速增加,與典型表現(xiàn)相符;另一部分患者瓣口面積增加,而跨瓣壓差和流速無明顯增加,可判定為“假性”的重度主動(dòng)脈瓣狹窄。臨床上,需要鑒別此類患者是否存在“假性”的主動(dòng)脈瓣的重度狹窄。在2014年美國心臟學(xué)會(huì)/美國心臟病學(xué)會(huì)(AHA/ACC)發(fā)布的心臟瓣膜病指南中,對(duì)主動(dòng)脈瓣狹窄(AS)作出了分期:A:AS風(fēng)險(xiǎn)期;B:AS進(jìn)展期;C1:無癥狀嚴(yán)重AS期;C2:無癥狀嚴(yán)重AS期合并左室功能障礙;D1:有癥狀嚴(yán)重AS合并高跨瓣壓差;D2:有癥狀嚴(yán)重AS合并低跨瓣血流量(或低跨瓣壓差)及LVEF降低;D3:有癥狀嚴(yán)重AS合并低跨瓣壓差及LVEF正常,或嚴(yán)重AS合并跨瓣血流量反常性降低[8]。Fougères等[9]隨訪了107例未接受手術(shù)治療的重度主動(dòng)脈瓣狹窄患者,發(fā)現(xiàn)“假性”重度主動(dòng)脈瓣狹窄組的預(yù)后明顯優(yōu)于“真性”重度主動(dòng)脈瓣狹窄伴或不伴左室功能衰竭兩組的患者。3組患者的5年死亡率分別為43%±11%、91%±6%及100%,P<0.001,提示此類患者的治療策略應(yīng)有別于“真性”主動(dòng)脈瓣重度狹窄患者。因此,該指南推薦,對(duì)于有癥狀重度主動(dòng)脈瓣狹窄伴左室功能不全,且超聲心動(dòng)圖或侵入性血流動(dòng)力學(xué)檢測(cè)符合以下特征的患者行低劑量多巴酚丁胺試驗(yàn)(Ⅱa類推薦、B級(jí)證據(jù)):(1)鈣化的主動(dòng)脈瓣使收縮期瓣膜開放受限;(2)LVEF<50%;(3)計(jì)算的主動(dòng)脈瓣瓣口面積≤1.0 cm2;(4)主動(dòng)脈瓣流速<4 m/s或平均跨瓣壓差<40 mmHg[8]。這有助于鑒別因左室心肌收縮功能不全或后負(fù)荷增加引起心輸出量減少,導(dǎo)致主動(dòng)脈瓣瓣口面積的低估[10]。此外,低劑量多巴酚丁胺試驗(yàn)還能評(píng)估這類患者的左心功能儲(chǔ)備情況,對(duì)于外科手術(shù)的風(fēng)險(xiǎn)評(píng)估及預(yù)后判斷具有重要價(jià)值[11-12]。
目前,尚缺乏針對(duì)TAVI的危險(xiǎn)分層以及死亡率預(yù)測(cè)的評(píng)估工具,只是參照外科手術(shù)的危險(xiǎn)分層標(biāo)準(zhǔn)。EuroSCORE和STS-PROM模型是歐洲心臟病協(xié)會(huì)(ESC)和美國胸外科協(xié)會(huì)(STS)提供的在線評(píng)分工具。計(jì)算EuroSCORE和STS-PROM預(yù)測(cè)的住院病死率,以篩選SAVR高?;颊?。預(yù)測(cè)死亡率Logistic EuroSCORE >20%、STS-PROM >10%、EuroSCORE Ⅱ≥7%為高危組[13]。手術(shù)風(fēng)險(xiǎn)評(píng)估還應(yīng)考慮到該評(píng)分系統(tǒng)未涉及的其他危險(xiǎn)因素,如胸部放療、主動(dòng)脈-冠狀動(dòng)脈搭橋手術(shù)史、瓷化主動(dòng)脈(porcelain aorta,指主動(dòng)脈大范圍鈣化)、肝硬化等[14]。
左室功能不全是重度主動(dòng)脈瓣狹窄患者SAVR圍術(shù)期和遠(yuǎn)期死亡的重要預(yù)測(cè)因子[15-16]。隨著現(xiàn)代外科技術(shù)的發(fā)展,單純合并左室功能不全的重度主動(dòng)脈瓣狹窄已不再是SAVR的禁忌證[17]。Chukwuemeka等[17]的回顧性研究表明,在132例左室射血分?jǐn)?shù)(LVEF)<40%的接受SAVR的患者(45%為重度主動(dòng)脈瓣狹窄,其余為主動(dòng)脈瓣關(guān)閉不全)中,圍術(shù)期死亡率僅2.3%,1年、5年、10年的生存率分別為96%、79%和55%。另一項(xiàng)研究納入2 563例同時(shí)接受SAVR和冠狀動(dòng)脈旁路移植術(shù)(CABG)的患者,結(jié)果顯示,重度左室功能不全組、中度左室功能不全組及左室功能正常組的術(shù)后30 d死亡率分別為9.0%、4.3% 和 2.9%,5年死亡率分別為36.3%、22.9%和17.5%(P<0.001)[18]。表明左室功能不全是SAVR預(yù)后的獨(dú)立危險(xiǎn)因子,是評(píng)估患者進(jìn)行SAVR風(fēng)險(xiǎn)的重要指標(biāo)。
TAVI是針對(duì)無法進(jìn)行SAVR或外科手術(shù)高?;颊叩囊环N治療手段。研究證實(shí),TAVI對(duì)重度主動(dòng)脈瓣狹窄患者預(yù)后的改善不亞于SAVR[19-20]。但對(duì)于合并嚴(yán)重左室功能不全的重度主動(dòng)脈瓣狹窄患者,接受TAVI治療的預(yù)后以及左室功能不全對(duì)患者預(yù)后影響的相關(guān)研究較少。
一項(xiàng)單中心研究表明,在左室功能不全(LVEF≤30%)和左室功能正常(LVEF>30%)的重度主動(dòng)脈瓣狹窄患者中,TAVI術(shù)后30 d的復(fù)合終點(diǎn)無顯著差異(21.0% 對(duì) 27.0%,P= 0.40);合并左室功能不全的患者在TAVI術(shù)后,左室功能顯著改善(LVEF從25%±4%提高至34%±10%,P= 0.002),兩組的遠(yuǎn)期生存率無差異(P= 0.29);而選擇藥物治療的重度主動(dòng)脈瓣狹窄伴左室功能不全的患者中,死亡率明顯升高(Log-rankP= 0.001)[21]。研究發(fā)現(xiàn),重度主動(dòng)脈瓣狹窄伴左室功能不全患者的SAVR風(fēng)險(xiǎn)評(píng)分更高(Logistic EuroSCORE 22.8% 對(duì)14.8%,P=0.012),但兩組住院或術(shù)后30 d死亡率、復(fù)合終點(diǎn)、術(shù)后1年無事件再住院率均無明顯差異[22]。這提示嚴(yán)重左室功能不全對(duì)接受TAVI的重度主動(dòng)脈瓣狹窄患者圍術(shù)期及遠(yuǎn)期預(yù)后的影響尚待進(jìn)一步研究,借助SAVR的風(fēng)險(xiǎn)評(píng)估工具并不能準(zhǔn)確預(yù)測(cè)接受TAVI治療患者的預(yù)后。PARTNER研究顯示,合并左室功能不全(LVEF<50%)的外科手術(shù)風(fēng)險(xiǎn)評(píng)估高危的重度主動(dòng)脈瓣狹窄患者中,TAVI組和SAVR組術(shù)后30 d和1年全因死亡率相似;1年后,兩組患者的平均LVEF均較基線顯著改善,TAVR組從35.7%±8.5%提高至48.6%±11.3% (P<0.0001);SAVR組從38.0%±8.0%提高至50.1%±10.8% (P<0.0001)[23]。OBSERVANT研究在近期也公布了短期結(jié)果,入選的162例LVEF<35%患者中,接受TAVI和SAVR的兩組患者30 d死亡率、急性心肌梗死、卒中、低心輸出量狀態(tài)、腎功能不全、術(shù)后重癥監(jiān)護(hù)病房和住院時(shí)間均無差異[24]。
左室功能不全是SAVR手術(shù)相關(guān)死亡或其他嚴(yán)重不良事件的獨(dú)立危險(xiǎn)因子,但并非侵入性更小、對(duì)血流動(dòng)力學(xué)影響更小的TAVI的禁忌證或預(yù)測(cè)因子,甚至可能是優(yōu)先選擇TAVI的適應(yīng)證。嚴(yán)重的左室功能不全對(duì)接受TAVI治療的重度主動(dòng)脈瓣狹窄患者預(yù)后的影響還有待研究。
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(收稿:2014-10-23 修回:2014-12-05)
(本文編輯:孫 雯)
361000 廈門市心臟中心
王 焱,Email:wy@medmail.com.cn
10.3969/j.issn.1673-6583.2015.01.012