闞通綜述秦永文審校

(第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院心血管內(nèi)科, 上海200433)

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二尖瓣反流診治進(jìn)展

闞通 綜述秦永文 審校

(第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院心血管內(nèi)科, 上海200433)

二尖瓣關(guān)閉功能取決于瓣葉、瓣環(huán)、腱索、乳頭肌和左心室的結(jié)構(gòu)完整和功能正常，影響到這些結(jié)構(gòu)的疾病都可以導(dǎo)致嚴(yán)重的二尖瓣反流(mitral regurgitation，MR)，降低患者的生存時(shí)間[1-3]。在西方國(guó)家，MR是常見(jiàn)的心臟瓣膜病[4]。

2014年3月，美國(guó)心臟協(xié)會(huì)與美國(guó)心臟病學(xué)會(huì)發(fā)表的心臟瓣膜病管理指南對(duì)慢性原發(fā)性(退行性)MR和慢性繼發(fā)性(功能性)MR進(jìn)行了明確區(qū)分[5]。慢性原發(fā)性MR由瓣葉、瓣環(huán)、腱索和乳頭肌1項(xiàng)或以上發(fā)生病理學(xué)改變引起；慢性繼發(fā)性MR繼發(fā)于左心室功能異常，二尖瓣膜通常是正常的。左心室異常擴(kuò)張引起乳頭肌移位，致瓣葉腱索過(guò)度緊張，最終導(dǎo)致MR。原發(fā)性和繼發(fā)性MR在病理生理學(xué)、預(yù)后、決策與管理上是完全不同的。在工業(yè)化國(guó)家，原發(fā)性MR最常見(jiàn)的病因是二尖瓣退行性變，不常見(jiàn)的病因是風(fēng)濕性心臟病和先天性畸形，發(fā)展中國(guó)家風(fēng)濕性心臟病較普遍[6]。繼發(fā)性MR使擴(kuò)張型心肌病患者的預(yù)后惡化[7]，缺血性MR是功能性MR的一種，其左心室功能紊亂繼發(fā)于心肌梗死。重度MR的自然病程不容樂(lè)觀，可引起左心室衰竭、肺動(dòng)脈高壓、心房顫動(dòng)、腦卒中和死亡[8]。

1 MR的分期

美國(guó)心臟協(xié)會(huì)與美國(guó)心臟病學(xué)會(huì)發(fā)表的心臟瓣膜病管理指南對(duì)MR進(jìn)行了分期。原發(fā)性MR和繼發(fā)性MR都可依據(jù)瓣膜的解剖學(xué)改變、瓣膜的血流動(dòng)力學(xué)及其結(jié)局和相關(guān)癥狀等分為4個(gè)漸進(jìn)階段。A期：危險(xiǎn)期；B期：進(jìn)展期；C期：無(wú)癥狀重度病變期；D期：有癥狀重度病變期(見(jiàn)表1、表2)。

表1 原發(fā)性MR分期

*許多評(píng)估瓣膜血流動(dòng)力學(xué)的標(biāo)準(zhǔn)被用以評(píng)估MR的嚴(yán)重程度，但并非所有標(biāo)準(zhǔn)都能在每個(gè)級(jí)別患者身上呈現(xiàn)。MR的嚴(yán)重程度通常分為輕、中、重度，取決于數(shù)據(jù)的質(zhì)量以及其他臨床證據(jù)。

表2 繼發(fā)性MR分期

*許多評(píng)估瓣膜血流動(dòng)力學(xué)的標(biāo)準(zhǔn)被用以評(píng)估MR的嚴(yán)重程度，但并非所有標(biāo)準(zhǔn)都能在每個(gè)級(jí)別患者身上呈現(xiàn)。MR的嚴(yán)重程度通常分為輕、中、重度，取決于數(shù)據(jù)的質(zhì)量以及其他臨床證據(jù)。

#可通過(guò)二維經(jīng)胸心臟超聲進(jìn)行等速表面積法計(jì)算繼發(fā)性MR患者的有效反流口面積，但由于該孔常為新月形，測(cè)得值常低于真實(shí)值。

2 MR的診斷

2.1 慢性原發(fā)性MR

推薦使用經(jīng)胸心臟超聲對(duì)任何懷疑患有慢性原發(fā)性MR的患者(A～D期)進(jìn)行如左心室大小和功能、右心室功能、左心房大小、肺動(dòng)脈壓力，以及MR的程度及可能原因的基本評(píng)估(Ⅰ，證據(jù)B)[9-13]；若經(jīng)胸心臟超聲無(wú)法確定原發(fā)性MR患者的左右心室容量、功能及反流的程度時(shí)，推薦使用心臟核磁共振幫助評(píng)估上述指標(biāo)(Ⅰ，證據(jù)B)[14-15]；推薦手術(shù)中使用經(jīng)食管超聲心動(dòng)圖以評(píng)估慢性原發(fā)性MR(C、D期)的解剖結(jié)構(gòu)，指導(dǎo)修復(fù)方案的制定(Ⅰ，證據(jù)B)[16]；當(dāng)非創(chuàng)傷性影像檢查提供的診斷信息不足時(shí)，推薦使用經(jīng)胸心臟超聲以判斷慢性原發(fā)性MR的嚴(yán)重程度(B～D期)、發(fā)病機(jī)制及左心室功能狀態(tài)(Ⅰ，證據(jù)C)。

2.2 慢性繼發(fā)性MR

通過(guò)經(jīng)胸心臟超聲可評(píng)估慢性繼發(fā)性MR(B～D期)的嚴(yán)重程度和病因、瓣膜運(yùn)動(dòng)異常的程度和位置、左心室功能及肺動(dòng)脈高壓等級(jí)(Ⅰ，證據(jù)C)。無(wú)創(chuàng)的影像學(xué)檢查(如壓力原子/電子斷層掃描、心臟核磁共振、負(fù)荷超聲心動(dòng)圖)，心臟增強(qiáng)CT，心導(dǎo)管檢查(包括冠狀動(dòng)脈造影術(shù))等，有助于明確慢性繼發(fā)性MR(B～D期)的病因及評(píng)估心肌活性，進(jìn)而為制定MR的治療方案提供決策參考(Ⅰ，證據(jù)C)。

3 MR的治療

3.1 藥物治療

對(duì)有癥狀的慢性原發(fā)性MR(D期)患者，若其射血分?jǐn)?shù)<60%，但無(wú)手術(shù)指征時(shí)，可用藥物治療以改善左心室的收縮功能(Ⅱa，證據(jù)B)[17-18]；不推薦對(duì)無(wú)癥狀和左心室收縮功能正常的慢性原發(fā)性MR(B和C1期)患者使用血管舒張劑(Ⅲ，證據(jù)B)[19-20]。

對(duì)慢性繼發(fā)性MR(B～D期)患者，若其伴有左心室射血分?jǐn)?shù)降低的心力衰竭，則需要給予指南推薦的藥物治療方案，以改善其心功能。常見(jiàn)的藥物有：血管緊張素轉(zhuǎn)換酶抑制劑、血管緊張素受體拮抗劑、β受體阻滯劑和醛固酮拮抗劑等(Ⅱ，證據(jù)A)[21-22]。

3.2 起搏器治療

對(duì)有癥狀的慢性繼發(fā)性MR(B～D期)患者，若滿足安置起搏器的指征，則推薦采用左右雙起搏療法(Ⅱ，證據(jù)A)[23]。

3.3 手術(shù)治療

及時(shí)適當(dāng)?shù)募m正退行性MR可顯著改善患者預(yù)后，甚至可使患者獲得同普通人群相似的預(yù)期壽命和生活質(zhì)量[24]。目前指南推薦有癥狀的重度原發(fā)性MR患者接受手術(shù)治療(推薦類型：Ⅰ級(jí))，伴有左心室功能衰竭無(wú)癥狀患者接受手術(shù)治療(推薦類型：Ⅰ級(jí))，左心室功能正常的無(wú)癥狀患者如果成功修復(fù)可能性大接受手術(shù)治療(推薦類型：Ⅱa級(jí))[5, 25]。有癥狀的繼發(fā)性MR患者接受最佳藥物治療后也可考慮手術(shù)治療(推薦類型：Ⅱb級(jí))。歐洲心臟病協(xié)會(huì)和美國(guó)心臟病學(xué)會(huì)頒布的指南在左心室功能障礙和幾項(xiàng)推薦的證據(jù)等級(jí)上稍有不同。

雖然有癥狀的重度MR患者沒(méi)有手術(shù)治療和藥物治療的隨機(jī)對(duì)照研究，觀測(cè)到的數(shù)據(jù)已表明手術(shù)治療可提高生存率[26]。

3.4 經(jīng)導(dǎo)管途徑治療

手術(shù)治療伴隨著1%～5%的病死率和10%～20%包括腦卒中、再次手術(shù)、腎功能衰竭和吸氧時(shí)間延長(zhǎng)的發(fā)生率[27]。在合并左心室功能障礙的老年患者中更是如此；80～89歲的患者手術(shù)后病死率達(dá)17%，超過(guò)1/3的患者發(fā)生術(shù)后并發(fā)癥[28]。由左心室功能障礙引起的繼發(fā)性MR患者，無(wú)論是否接受手術(shù)治療生存率較原發(fā)性患者低。通過(guò)外科二尖瓣成形術(shù)未提高繼發(fā)性MR患者的生存率。無(wú)論是缺血性和不缺血性的功能性MR，年齡和并發(fā)癥對(duì)患者生存率影響最大。創(chuàng)傷小、并發(fā)癥少、費(fèi)用少的經(jīng)導(dǎo)管途徑治療MR的方法將更加適合老年、高風(fēng)險(xiǎn)患者。

目前只有美國(guó)雅培公司的Mitra Clip一種經(jīng)導(dǎo)管途徑裝置被批準(zhǔn)用于臨床治療繼發(fā)性MR。此設(shè)備在2013年10月被批準(zhǔn)應(yīng)用是基于隨機(jī)對(duì)照試驗(yàn)EVEREST Ⅱ的結(jié)果[29-31]。在EVEREST Ⅱ中來(lái)自37個(gè)中心的279例患者(73%為繼發(fā)性MR)被隨機(jī)分為接受經(jīng)皮二尖瓣修復(fù)組(n=184)和開(kāi)放手術(shù)二尖瓣修復(fù)組(n=95)。同開(kāi)放手術(shù)組相比經(jīng)皮二尖瓣修復(fù)組患者雖然療效略差，但安全性較高。同開(kāi)放手術(shù)組相比經(jīng)皮二尖瓣修復(fù)組患者需要再次手術(shù)解決殘留MR的患者較多，但1年隨訪后，兩組患者需再次手術(shù)的很少，4年后病死率兩組未見(jiàn)明顯差別[31]。

幾項(xiàng)研究表明，同開(kāi)放手術(shù)相比，雖然經(jīng)導(dǎo)管二尖瓣修復(fù)術(shù)在減少M(fèi)R上效果較差，但提高了不能手術(shù)或者高?；颊叩纳钯|(zhì)量和臨床轉(zhuǎn)歸[32-37]。

4 總結(jié)

MR是常見(jiàn)的心臟瓣膜病，依據(jù)病因可將MR分為原發(fā)性MR和繼發(fā)性MR，嚴(yán)重MR對(duì)患者危害極大。MR依據(jù)瓣膜的解剖學(xué)改變、瓣膜的血流動(dòng)力學(xué)及其結(jié)局和相關(guān)癥狀等分為A期：危險(xiǎn)期；B期：進(jìn)展期；C期：無(wú)癥狀重度病變期；D期：有癥狀重度病變期4個(gè)漸進(jìn)的階段。MR診斷主要依據(jù)經(jīng)胸心臟超聲，無(wú)創(chuàng)的影像學(xué)檢查(如壓力原子/電子斷層掃描、心臟核磁共振、負(fù)荷超聲心動(dòng)圖)，心臟增強(qiáng)CT，心導(dǎo)管檢查(包括冠狀動(dòng)脈造影術(shù))等。MR主要有藥物治療、起搏器治療、手術(shù)治療和經(jīng)導(dǎo)管途經(jīng)治療。經(jīng)導(dǎo)管二尖瓣修復(fù)術(shù)在減少M(fèi)R上效果較差，但提高了不能手術(shù)或者高?；颊叩纳钯|(zhì)量和臨床轉(zhuǎn)歸，是治療MR安全可靠的方法。

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Recent Progress in Diagnosis and Treatment of Mitral Regurgitation

KAN Tong, QIN Yongwen

(DepartmentofCardiology,ChanghaiHospital,TheSecondMilitaryMedicalUniversity,Shanghai200433,China)

影響二尖瓣關(guān)閉功能的疾病都可以導(dǎo)致二尖瓣反流。輕度二尖瓣反流患者僅有輕微勞力性呼吸困難，重度二尖瓣反流癥狀嚴(yán)重，降低患者的生存時(shí)間。目前依據(jù)病因可將二尖瓣反流分為原發(fā)性二尖瓣反流和繼發(fā)性二尖瓣反流，這兩種二尖瓣反流有不同的診斷和治療原則?，F(xiàn)就二尖瓣反流的診斷治療進(jìn)展做一綜述。

二尖瓣反流；二尖瓣；診斷；治療結(jié)果

The diseases that affect the function of mitral valve can lead to mitral regurgitation (MR). The patients with mild MR can only feel mild exertional dyspnea and the patients with severe MR can feel severe symptoms, which reduces the patients’ survival time. Presently, MR is classified into primary and secondary entities based on the pathogen. The diagnosis and treatment of the primary and secondary MR are quite different. This paper aims to make a comprehensive review about the recent progress in diagnosis and treatment of MR.

mitral regurgitation; mitral valve; diagnosis; treatment outcome

闞通(1990—)，在讀碩士，主要從事心血管病介入治療研究。Email: 871415868@qq.com

秦永文(1952—)，主任醫(yī)師，教授，博士，主要從事心血管病介入治療研究。Email: chqinyw@163.com

1004-3934(2015)06-0686-05

R542.5

A

10.3969/j.issn.1004-3934.2015.06.008

2015-06-02

2015-07-21