郭文杰，徐偉豪，張玉霄，盧才義*

（解放軍總醫(yī)院：1心血管內(nèi)科，2南樓心一科，北京 100853）

1 概 述

心房纖顫（簡(jiǎn)稱房顫）是臨床上最常見(jiàn)的房性心律失常之一，其發(fā)病率在全世界持續(xù)增長(zhǎng)[1]。它是卒中和心力衰竭的獨(dú)立危險(xiǎn)因素，房顫患者較竇性心律患者的死亡率增加3倍[2]。對(duì)于復(fù)發(fā)性房顫患者，抗心律失常藥物是轉(zhuǎn)復(fù)和預(yù)防復(fù)發(fā)的次要手段，而導(dǎo)管消融治療越來(lái)越受到人們的重視[3]。多項(xiàng)隨機(jī)對(duì)照臨床研究顯示，導(dǎo)管消融能更好地治療房顫、改善癥狀，提高生活質(zhì)量并有可能降低因房顫所致的血栓栓塞事件的發(fā)生風(fēng)險(xiǎn)[4]。目前，已有多項(xiàng)研究發(fā)現(xiàn)并證實(shí)了房顫觸發(fā)和維持的電生理和解剖靶位。Ha?ssaguerre等[5]發(fā)現(xiàn)起源于肺靜脈（pulmonary veins，PVs）的異位興奮灶可誘發(fā)陣發(fā)性房顫的發(fā)生，而對(duì)于大多數(shù)房顫，特別是陣發(fā)性房顫患者，經(jīng)驗(yàn)性肺靜脈隔離（pulmonary vein isolation，PVI）能夠治愈該病[7]。

最新指南推薦：（1）對(duì)于有癥狀的陣發(fā)性房顫患者或不能耐受至少一種Ⅰ類或Ⅲ類抗心律失常藥物的陣發(fā)性房顫患者，導(dǎo)管射頻消融治療是其首選治療方法；（2）對(duì)于持續(xù)性房顫患者，也推薦使用導(dǎo)管消融治療[8,9]。

與陣發(fā)性房顫相比，導(dǎo)管消融治療持續(xù)性房顫和長(zhǎng)時(shí)程房顫效果不理想，PVI后復(fù)發(fā)率高達(dá)60%[10]。所以，非陣發(fā)性房顫患者除了需要PVI治療外，還需要對(duì)其他靶點(diǎn)進(jìn)行消融，以達(dá)到治愈房顫、預(yù)防復(fù)發(fā)的目的[11]。本文旨在綜述持續(xù)性房顫射頻消融術(shù)中除PVI外的其他輔助消融技術(shù)。

2 線性消融

從胚胎學(xué)、解剖學(xué)和電生理學(xué)角度看，左房后壁可以認(rèn)為是PVs延續(xù)區(qū)[12]。外科手術(shù)已證實(shí)，左房后壁在房顫的觸發(fā)和維持上起著重要作用[13]，甚至有人認(rèn)為有些房顫起源僅局限于此[14,15]。Oral等[16]將80名慢性房顫患者隨機(jī)分成兩組，一組行PVI治療，另一組行非整環(huán)后壁線性消融治療。平均隨訪9個(gè)月，第一組術(shù)后復(fù)發(fā)率為28%，而另一組為25%（P＝0.8）。此外，姚焰采用步進(jìn)法左房線性消融持續(xù)性房顫研究中發(fā)現(xiàn)，左房房頂、左心耳嵴部和二尖瓣峽部消融能終止9.3%持續(xù)性房顫，在此基礎(chǔ)上行右側(cè)肺靜脈前庭線性消融及冠狀竇左心房側(cè)后壁線性消融能夠終止32.6%的持續(xù)性房顫，長(zhǎng)期隨訪成功率為72.1%。由此可見(jiàn)在PVI消融術(shù)同時(shí)增加線性消融，能提高手術(shù)成功率及竇性心律維持率。常見(jiàn)的線性消融位點(diǎn)包括左房頂部線、二尖瓣峽部線、三尖瓣峽部線、二尖瓣環(huán)左房后壁線和冠狀竇。

3 復(fù)雜碎裂心房電位（complex fractionated atrial electrograms，CFAE）消融

持續(xù)性房顫很可能并不是由PVs持續(xù)釋放異位電位所致。根據(jù)Moe等的“多發(fā)折返子波”假說(shuō)，持續(xù)性房顫時(shí)心房無(wú)規(guī)律電活動(dòng)是心房?jī)?nèi)多個(gè)獨(dú)立的折返子波在不應(yīng)期彌散分布于不均勻介質(zhì)中隨機(jī)擴(kuò)散的結(jié)果[17,18]。子波源于不同的慢傳導(dǎo)區(qū)域，圍繞解剖或功能位點(diǎn)旋轉(zhuǎn)并彼此相互碰撞，這種各異性的傳導(dǎo)就形成了CFAE[19]。雖然這些致房顫的復(fù)雜折返環(huán)隨機(jī)產(chǎn)生且不易準(zhǔn)確標(biāo)記，但該象充分表明房顫的觸發(fā)和維持機(jī)制可能與CFAE有關(guān)[12]。Nademanee等[14]首次系統(tǒng)描述了CFAE的特點(diǎn)，CFAE為低振幅電位（0.06到0.25mv），激動(dòng)周期≤120ms或短于冠狀竇周長(zhǎng)，有2～3個(gè)折返，連續(xù)無(wú)恒定基線的心房激動(dòng)波；并對(duì)包含所有類型的房顫患者行基于CFAE的射頻消融治療，隨訪1年成功率高達(dá)91%。

繼Nademanee等的研究之后，有許多研究都證實(shí)了CFAE消融在房顫消融中的輔助作用。Ha?saguerre等[14,15]將CFAE消融方法加入到他們對(duì)長(zhǎng)時(shí)程房顫患者的分步連續(xù)性消融中。分步消融包括PVI，左房房頂線性消融，冠狀竇及左房下壁消融，心房?jī)?nèi)高頻低幅CFAE消融和二尖瓣峽部、左心耳根部線性消融。消融過(guò)程中可觀察到所有患者都出現(xiàn)了房顫周期延長(zhǎng)現(xiàn)象，其中87%的病例消融后出現(xiàn)房性心動(dòng)過(guò)速，13%術(shù)中轉(zhuǎn)復(fù)竇性心律。房性心動(dòng)過(guò)速患者先標(biāo)記后消融，大多可以成功[15]。

Hunter等[20]首次將CFAE分級(jí)。Grade 1：連續(xù)碎裂電位。Grade 2：間斷碎裂電位。Grade 3：間歇性碎裂電位；Grade 4：復(fù)雜電位。Hunter等推測(cè)連續(xù)碎裂電活動(dòng)（Grade 1和2）可能與局灶機(jī)制相關(guān)，而少量的碎裂信號(hào)（Grade 4）更多地反應(yīng)了折返機(jī)制。間歇性碎裂電位（Grade 3）可能是一種被動(dòng)波，也可能是遠(yuǎn)場(chǎng)電位和局灶電位重疊所致，其對(duì)房顫的維持無(wú)明確意義。目前所有的研究結(jié)果都提示，CFAE消融對(duì)于非陣發(fā)性房顫患者預(yù)后有益。

無(wú)論是何種房顫類型，心房因素在房顫維持機(jī)制、術(shù)中電位標(biāo)記和導(dǎo)管消融上都越來(lái)越受到重視。Nademanee等[12]首次報(bào)道了對(duì)持續(xù)性房顫和長(zhǎng)時(shí)程房顫患者進(jìn)行CFAEs消融的成功率達(dá)91%。同一研究小組對(duì)674名患者持續(xù)2年隨訪的結(jié)果顯示CFAEs消融成功率為85%[21]。但這些研究都是非隨機(jī)研究，Oral等并沒(méi)有發(fā)現(xiàn)PVI后加CFAEs消融能提高患者竇性心律維持率[22]。根據(jù)本中心研究，CFAEs消融在系統(tǒng)PVI基礎(chǔ)上可能提高手術(shù)成功率及術(shù)后竇性心律維持率。

4 神經(jīng)節(jié)（叢）（gangllonated plexuses，GPs）消融

心臟自主神經(jīng)系統(tǒng)是機(jī)體自主神經(jīng)系統(tǒng)的一部分，包括交感神經(jīng)系統(tǒng)和副交感神經(jīng)系統(tǒng)。而GPs主要存在于心外膜脂肪墊中[23]，特別是PVs前庭中。右房和上腔靜脈交界處也存在著GPs之間以及GPs和心房心肌膜之間的廣泛連接[24]。

眾多研究已明確了自主神經(jīng)系統(tǒng)在房顫觸發(fā)和維持上的作用，其機(jī)制包括易化自主心房提早除極，縮短心房和PV有效不應(yīng)期等[25,26]。基于這一理論，許多學(xué)者認(rèn)為GPs消融是除PVI以外的重要輔助消融手段[21,27,28]。通常，GPs多可通過(guò)高頻刺激心房心內(nèi)膜后迷走反應(yīng)定位[21,28]。一項(xiàng)隨機(jī)性研究納入了67名陣發(fā)性房顫患者，他們被隨機(jī)分入PVI組和PVI＋GP消融組，平均隨訪10個(gè)月，PVI組中僅有45.5%的患者未復(fù)發(fā)，而PVI＋GP消融組則高達(dá)73.5%[29]。Pachon等[29]首次利用實(shí)時(shí)頻譜標(biāo)測(cè)系統(tǒng)快速有效地識(shí)別具有含高頻雙極心房電位的心肌區(qū)域（如房顫巢）。Arruda等[30]在一項(xiàng)前瞻性隨機(jī)研究中評(píng)估了房顫巢消融的輔助作用，結(jié)論是雖然加用房顫巢導(dǎo)致消融絕對(duì)獲益較少（陣發(fā)性房顫絕對(duì)危險(xiǎn)性減少9%，持續(xù)性房顫患者減少10%），但它仍能減少房顫復(fù)發(fā)。解剖學(xué)上，在PV前庭水平，自主神經(jīng)位點(diǎn)分布與CFAE分布吻合。因此，自主神經(jīng)節(jié)可以在傳統(tǒng)PVI消融或者是在CFAE消融中一并被有效消融[31]。

5 主頻率（dominant frequency，DF）消融

對(duì)房顫患者心房電位進(jìn)行電位標(biāo)測(cè)研究發(fā)現(xiàn)，房顫患者心房?jī)?nèi)總是存在從高DF區(qū)域到低DF區(qū)域的特有電位梯度。具有高DF的心房區(qū)域可能與房顫觸發(fā)和維持相關(guān)，故該區(qū)域可能是消融靶點(diǎn)[32]。Sanders等[33]對(duì)房顫患者的左房電位進(jìn)行實(shí)時(shí)頻譜標(biāo)測(cè)，并對(duì)高DF區(qū)域行射頻消融，術(shù)后發(fā)現(xiàn)房顫周期延長(zhǎng)[從（180±30）ms延長(zhǎng)到（198±40）ms；P＜0.0001，Kappa＝0.77]，19例陣發(fā)性房顫患者中有17例術(shù)中復(fù)律，持續(xù)性房顫患者無(wú)一例實(shí)現(xiàn)術(shù)中復(fù)律。Verma等[31]報(bào)道，與PVI消融組相比，PVI＋DF消融組在術(shù)后1年的無(wú)心律失常生存率上無(wú)差異。

6 轉(zhuǎn)子消融

目前有研究發(fā)現(xiàn)，房顫患者心房?jī)?nèi)存在一種穩(wěn)定快速的折返環(huán)，將其命名為“轉(zhuǎn)子”，而轉(zhuǎn)子也將成為房顫消融新的靶點(diǎn)[34]。加利福尼亞圣地亞哥大學(xué)的一項(xiàng)研究應(yīng)用64極籃狀電極標(biāo)測(cè)房顫患者左、右心房電位，并通過(guò)一種新型系統(tǒng)識(shí)別持續(xù)性轉(zhuǎn)子（旋轉(zhuǎn)波）和局灶電位（向心房周圍擴(kuò)散的離心電位）[35]。轉(zhuǎn)子是連續(xù)順時(shí)針或逆時(shí)針旋轉(zhuǎn)的活動(dòng)電位，它與房顫的維持息息相關(guān)。一旦發(fā)現(xiàn)轉(zhuǎn)子和局灶電位存在持續(xù)時(shí)間超過(guò)10min，就可以認(rèn)為它們是房顫產(chǎn)生的原因。CONFIRM（The Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation）研究首次提示房顫的維持可能與位置固定的轉(zhuǎn)子和局灶電位相關(guān)，其所在區(qū)域?yàn)樯漕l消融靶位。該研究將92名患者分為兩組，一組患者接受PVI消融治療（n＝71），另一組患者接受PVI消融和局灶電位、轉(zhuǎn)子消融（focal impulse and rotor modulation，F(xiàn)IRM）治療（n＝36）。97%的患者發(fā)現(xiàn)了位置固定的轉(zhuǎn)子和局灶電位，80%的轉(zhuǎn)子位于左房，20%位于右房。通過(guò)植入式事件記錄儀隨訪監(jiān)測(cè)顯示，PVI＋FIRM消融成功率高達(dá)82.4%，較PVI消融治療44.9%的成功率高（P＜0.001）。但Miller等[36]認(rèn)為，一旦心房容積超過(guò)籃狀標(biāo)測(cè)導(dǎo)管的最大體積時(shí)，這種標(biāo)測(cè)方法的可靠性就值得商榷了。是否所有類型房顫患者都存在轉(zhuǎn)子，消融后是否可明顯改善預(yù)后，目前許多研究都在積極證實(shí)之中。

7 非肺靜脈觸發(fā)位點(diǎn)消融

非PV觸發(fā)位點(diǎn)在PVI術(shù)后復(fù)發(fā)、特別是非陣發(fā)性房顫PVI術(shù)后復(fù)發(fā)中起到了重要作用。非肺靜脈觸發(fā)位點(diǎn)大多存在于心房游離壁、界嵴、房室交界區(qū)、冠狀竇、Marshall韌帶、左心耳中。消融Marshall韌帶通?？蓮淖蠓肯卤谛膬?nèi)膜面消融至左下肺靜脈入口，也可通過(guò)導(dǎo)絲和球囊經(jīng)Marshall靜脈灌注酒精以達(dá)到有效的Marshall韌帶的電隔離作用。Di Biase等[37]發(fā)現(xiàn)三分之一的房顫復(fù)發(fā)患者均存在左心耳觸發(fā)位點(diǎn)。一旦發(fā)現(xiàn)左心耳中存在觸發(fā)灶，應(yīng)對(duì)其行完全電隔離才能保證手術(shù)成功。

8 結(jié) 論

PVI治療是目前房顫射頻消融治療的基石，特別是在陣發(fā)性房顫中效果明確[38]。但對(duì)于持續(xù)性房顫和長(zhǎng)時(shí)程房顫，單行PVI治療，手術(shù)成功率及術(shù)后竇性心律維持率較低。近年來(lái)，除PVI以外的輔助消融技術(shù)得到了廣泛的研究。通過(guò)研究發(fā)現(xiàn)，廣泛線性消融、心房CFAE消融、轉(zhuǎn)子消融及非肺靜脈觸發(fā)位點(diǎn)消融可以提高非陣發(fā)性房顫患者的手術(shù)成功率及術(shù)后竇性心律的維持率。但這些輔助消融方法仍需要更多的隨機(jī)化研究來(lái)證實(shí)其優(yōu)勢(shì)。老年人群中非陣發(fā)性房顫發(fā)生率較青年人群高，單純使用PVI消融治療效果欠佳，更多的老年患者需要加用輔助消融策略，從而提高消融成功率，但是否會(huì)增加手術(shù)風(fēng)險(xiǎn)，仍需要更多的臨床研究加以證實(shí)。

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