李景業(yè) 杜昕 龍德勇 蔣晨曦 郭雪原 張婷 李新 董建增 馬長(zhǎng)生
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·臨床研究·
導(dǎo)管消融與藥物治療對(duì)肥厚型心肌病合并心房顫動(dòng)患者心血管原因住院率的影響
李景業(yè) 杜昕 龍德勇 蔣晨曦 郭雪原 張婷 李新 董建增 馬長(zhǎng)生
目的 探討導(dǎo)管消融與藥物治療對(duì)肥厚型心肌病(hypertrophic cardiomyopathy,HCM)合并心房顫動(dòng)(房顫)患者心血管原因住院率的影響。方法 連續(xù)入選2004年6月至2015年3月于首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院等7家醫(yī)院首次接受導(dǎo)管消融治療的48例HCM合并房顫患者作為導(dǎo)管消融組,納入同期僅接受藥物治療的78例HCM合并房顫患者作為藥物治療組。隨訪觀察患者房顫復(fù)發(fā)及心血管原因住院情況。結(jié)果 導(dǎo)管消融組48例患者均順利完成房顫導(dǎo)管消融,單次術(shù)后平均隨訪(17.6±8.4)個(gè)月,16例(33.3%)復(fù)發(fā)房顫,32例(66.7%)維持竇性心律;藥物治療組平均隨訪(10.7±8.0)個(gè)月,31例(39.7%)轉(zhuǎn)復(fù)為竇性心律;導(dǎo)管消融組患者竇性心律維持率顯著高于藥物治療組,差異有統(tǒng)計(jì)學(xué)意義(P=0.003)。與藥物治療組相比,導(dǎo)管消融組的非計(jì)劃性心血管原因住院率顯著降低[2例(4.2%)比17例(21.8%),P=0.001]。Cox多因素分析顯示,房顫治療策略(導(dǎo)管消融/藥物治療,HR9.082,95%CI1.130~73.011,P=0.038)和既往心力衰竭史(HR2.860,95%CI1.072~7.633,P=0.036)是非計(jì)劃性心血管原因住院的獨(dú)立危險(xiǎn)因素。結(jié)論 HCM合并房顫組患者導(dǎo)管消融治療的竇性心律維持率及非計(jì)劃性心血管原因住院率均優(yōu)于藥物治療組患者,房顫治療策略和既往心力衰竭史是非計(jì)劃性心血管原因住院的獨(dú)立危險(xiǎn)因素。
肥厚型心肌??; 心房顫動(dòng); 導(dǎo)管消融; 藥物; 心血管原因住院
肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是一種與基因遺傳有關(guān)的心血管疾病,易發(fā)生各種心律失常,其中心房顫動(dòng)(房顫)是最為常見的一種,可顯著增加心力衰竭、卒中的發(fā)生率,嚴(yán)重影響患者的生存質(zhì)量[1]。《2014年歐洲心臟病學(xué)會(huì)(European society of cardiology,ESC)HCM診斷和管理指南》[1]及《2011年美國心臟病學(xué)會(huì)基金會(huì)(American college of cardiology foundation,ACCF)/美國心臟協(xié)會(huì)(American heart association,AHA)HCM診斷和治療指南》[2]均推薦在規(guī)律抗凝的基礎(chǔ)上積極予以轉(zhuǎn)復(fù)竇性心律或控制心室率治療。然而,現(xiàn)有抗心律失常藥物尚不能有效根治房顫,藥物的潛在不良反應(yīng)亦限制其長(zhǎng)期應(yīng)用[3]。近年來,導(dǎo)管消融技術(shù)在臨床實(shí)踐中逐步取得進(jìn)展,已成為房顫治療的重要手段[4]。HCM合并房顫患者接受導(dǎo)管消融治療能否有效改善其臨床預(yù)后,導(dǎo)管消融與藥物治療相比是否具備一定優(yōu)勢(shì),目前仍無定論。本研究在分析HCM合并房顫患者導(dǎo)管消融與藥物治療有效性的基礎(chǔ)上對(duì)其非計(jì)劃性心血管原因住院的危險(xiǎn)因素進(jìn)行探討。
1.1 研究對(duì)象
連續(xù)入選2004年6月至2015年3月于首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院等7家醫(yī)院首次接受導(dǎo)管消融治療的48例HCM合并房顫患者作為導(dǎo)管消融組,納入同期僅接受藥物治療的78例HCM合并房顫患者作為藥物治療組。陣發(fā)性和持續(xù)性房顫均可入選。陣發(fā)性房顫定義為房顫發(fā)作時(shí)間小于7 d,可自行轉(zhuǎn)復(fù)竇性心律。持續(xù)性房顫定義為房顫發(fā)作時(shí)間大于7 d,或7 d內(nèi)需藥物治療或電復(fù)律方可轉(zhuǎn)復(fù)竇性心律。HCM診斷標(biāo)準(zhǔn)[1]:經(jīng)超聲心動(dòng)圖、核磁共振成像或左心室造影證實(shí)左心室最厚室壁厚度≥15 mm;若靜息狀態(tài)下左心室流出道壓力階差≥30 mmHg(1 mmHg=0.133 kPa),提示流出道梗阻;同時(shí)需排除可能引起相同程度左心室肥厚的其他疾病。排除標(biāo)準(zhǔn):(1)合并瓣膜??;(2)合并先天性心臟??;(3)左心耳血栓;(4)存在抗凝禁忌證。
1.2 電生理檢查和導(dǎo)管消融
導(dǎo)管消融術(shù)前停用所有抗心律失常藥物至少5個(gè)半衰期,其中胺碘酮停用4周以上。術(shù)前24 h內(nèi)經(jīng)食管超聲心動(dòng)圖和(或)心臟64排CT排除左心房血栓,規(guī)律皮下注射低分子肝素抗凝。術(shù)前所有患者簽署知情同意書。術(shù)中清醒狀態(tài)下行局部麻醉,持續(xù)靜脈泵入芬太尼和咪達(dá)唑侖鎮(zhèn)靜。研究納入的HCM合并房顫患者近80%(38/48)來自首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院房顫中心,本中心行單導(dǎo)管房顫射頻消融的具體方法已有詳細(xì)報(bào)道[5],簡(jiǎn)述如下:陣發(fā)性房顫在CARTO三維電解剖標(biāo)測(cè)系統(tǒng)指導(dǎo)下行雙側(cè)環(huán)肺靜脈前庭隔離。術(shù)前、術(shù)中合并典型心房撲動(dòng)(房撲)者同時(shí)行三尖瓣峽部線性消融。持續(xù)性房顫在雙側(cè)肺靜脈隔離基礎(chǔ)上進(jìn)一步行左心房頂部線、二尖瓣峽部線、三尖瓣峽部線消融或碎裂電位消融。若消融未能使房顫轉(zhuǎn)復(fù)為竇性心律,行體外直流電復(fù)律(200 J)。竇性心律下單導(dǎo)管補(bǔ)點(diǎn),證實(shí)雙側(cè)肺靜脈電隔離、消融徑線雙向阻滯。
1.3 術(shù)后隨訪
如無禁忌,導(dǎo)管消融術(shù)后需服用抗心律失常藥物3個(gè)月,未復(fù)發(fā)者可停藥。術(shù)后常規(guī)口服華法林抗凝至少3個(gè)月,維持國際標(biāo)準(zhǔn)化比值(INR)2.0~3.0。術(shù)后1、3、6個(gè)月及以后每6個(gè)月常規(guī)行標(biāo)準(zhǔn)12導(dǎo)聯(lián)心電圖和24 h動(dòng)態(tài)心電圖檢查。隨訪期內(nèi)若出現(xiàn)心悸、氣短等癥狀,隨時(shí)門診就診行心電圖檢查。術(shù)后3個(gè)月設(shè)為空白期。導(dǎo)管消融組房顫復(fù)發(fā)定義為空白期后未服用抗心律失常藥物時(shí),經(jīng)標(biāo)準(zhǔn)12導(dǎo)聯(lián)心電圖或24 h動(dòng)態(tài)心電圖證實(shí)的持續(xù)時(shí)間在30 s以上的房顫、房撲、房性心動(dòng)過速(房速)等快速房性心律失常。藥物治療組房顫發(fā)作即為經(jīng)標(biāo)準(zhǔn)12導(dǎo)聯(lián)心電圖或24 h動(dòng)態(tài)心電圖證實(shí)的持續(xù)時(shí)間在30 s以上的房顫、房撲、房性心動(dòng)過速(房速)等快速房性心律失常。
1.4 統(tǒng)計(jì)學(xué)分析
2.1 兩組患者基線資料比較
與藥物治療組相比,導(dǎo)管消融組患者的年齡[(55.5±9.9)歲比(66.8±13.3)歲,P<0.001]、既往心力衰竭[0比19例(24.4%),P<0.001]和卒中病史[6例(12.5%)比27例(34.6%),P=0.007]患者所占比例均顯著較低,差異均有統(tǒng)計(jì)學(xué)意義。兩組患者的性別、房顫病程、房顫類型、肥厚型心肌病病程、梗阻性肥厚型心肌病、體重指數(shù)、其他心血管疾病危險(xiǎn)因素、超聲心動(dòng)圖指標(biāo)等臨床資料比較,差異均無統(tǒng)計(jì)學(xué)意義(均P>0.05,表1)。
表1 兩組患者的基線資料比較
2.2 兩組患者竇性心律維持率比較
圖1 兩組患者竇性心律維持率Kaplan-Meier生存曲線
導(dǎo)管消融組48例患者均順利完成房顫導(dǎo)管消融,單次術(shù)后平均隨訪(17.6±8.4)個(gè)月,共16例(33.3%)患者復(fù)發(fā)房顫,其中10例(20.8%)患者再次接受導(dǎo)管消融治療。導(dǎo)管消融組共2例(4.2%)患者出現(xiàn)手術(shù)相關(guān)并發(fā)癥,1例在接受二次消融時(shí)發(fā)生心臟壓塞,經(jīng)外科手術(shù)成功修補(bǔ);另1例出現(xiàn)股靜脈穿刺處血腫,隨訪至2個(gè)月時(shí)已完全吸收。藥物治療組平均隨訪(10.7±8.0)個(gè)月,31例(39.7%)患者轉(zhuǎn)復(fù)為竇性心律。導(dǎo)管消融組患者竇性心律維持率[66.7%(32/48)比39.7%(31/79)]顯著高于藥物治療組,差異有統(tǒng)計(jì)學(xué)意義(P=0.003,圖1)。
2.3 兩組患者藥物使用情況比較
導(dǎo)管消融組空白期過后未復(fù)發(fā)房顫者可常規(guī)停用抗心律失常藥物治療。至隨訪結(jié)束時(shí),導(dǎo)管消融組的β阻滯藥使用率顯著低于藥物治療組[8例(16.7%)比61例(78.2%),P<0.001];地高辛使用率亦顯著低于藥物治療組[0比15例(19.2%),P=0.001]。非二氫吡啶類鈣離子拮抗藥使用率方面,導(dǎo)管消融組較藥物治療組呈降低趨勢(shì),但差異無統(tǒng)計(jì)學(xué)意義[7例(14.6%)比23例(29.5%),P=0.084]??紤]到導(dǎo)管消融組隨訪期間有16例患者復(fù)發(fā)房顫,其中11例仍需口服胺碘酮控制節(jié)律,故在此類藥物的使用率上較藥物治療組差異無統(tǒng)計(jì)學(xué)意義[11例(22.9%)比17例(21.8%),P=1.000,表2]。
表2 兩組患者的藥物使用情況比較[例(%)]
2.4 兩組患者心血管原因住院情況比較
隨訪期間,導(dǎo)管消融組共5例(10.4%)患者因心血管原因再住院,其中3例(6.2%)為再次行導(dǎo)管消融擇期住院,2例(4.2%)因快速心律失常住院。藥物治療組共19例(24.4%)患者因心血管原因住院,其中2例(2.6%)擇期住院治療房顫,5例(6.4%)因快速心律失常住院,1例(1.3%)因竇性心動(dòng)過緩住院,3例(3.8%)因卒中住院,1例(1.3%)因INR不達(dá)標(biāo)消化道出血住院,7例(9.0%)因心力衰竭住院。雖然兩組間因擇期治療房顫住院的患者比例比較,差異無統(tǒng)計(jì)學(xué)意義(6.2%比2.6%,P=0.368),但導(dǎo)管消融組的非計(jì)劃性心血管原因住院率顯著低于藥物治療組(4.2%比21.8%,P=0.001,圖2,表3)。
圖2 兩組患者非計(jì)劃性心血管原因住院率的Kaplan-Meier曲線
心血管原因住院導(dǎo)管消融組(48例)藥物治療組(78例)P值計(jì)劃性住院/消融相關(guān)3(62)2(26)0368非計(jì)劃性住院2(42)17(218)0001 快速心律失常2(42)5(64) 竇性心動(dòng)過緩0(0)1(13) 卒中0(0)3(38) 出血0(0)1(13) 心力衰竭0(0)7(90)
2.5 非計(jì)劃性心血管原因住院相關(guān)因素
Cox單因素分析顯示,HCM合并房顫患者非計(jì)劃性心血管原因住院與年齡、房顫類型、房顫治療策略(導(dǎo)管消融/藥物治療)、既往心力衰竭和卒中病史相關(guān)(P<0.05,表4)。將上述因素逐步代入Cox多因素回歸分析,結(jié)果顯示,房顫治療策略(HR9.082,95%CI1.130~73.011,P=0.038)和既往心力衰竭(HR2.860,95%CI1.072~7.633,P=0.036)是非計(jì)劃心血管原因住院的獨(dú)立危險(xiǎn)因素(表5)。
本研究對(duì)126例HCM合并房顫患者行導(dǎo)管消融和接受藥物治療的臨床預(yù)后進(jìn)行了比較,結(jié)果發(fā)現(xiàn):HCM合并房顫患者接受導(dǎo)管消融治療安全可行,單次消融術(shù)后的竇性心律維持率顯著高于藥物治療組;消融術(shù)后HCM患者的β阻滯藥和地高辛使用率大幅減少,非計(jì)劃性心血管原因住院率顯著降低。本組HCM患者中,房顫治療策略和既往心力衰竭是非計(jì)劃性心血管原因住院的獨(dú)立危險(xiǎn)因素。
房顫是HCM最常見的并發(fā)癥之一,患病率達(dá)20%~25%[6-7]。房顫的發(fā)生標(biāo)志著臨床癥狀惡化的開始,提示患者短期及長(zhǎng)期預(yù)后不佳[8]。HCM合并房顫患者出現(xiàn)中-重度心力衰竭(NYHA分級(jí)Ⅲ~Ⅳ級(jí))的風(fēng)險(xiǎn)是竇性心律維持者的3倍[9],其心力衰竭住院率較無房顫者顯著增加(39.0%比15.4%)[10]。合并房顫后,HCM患者的卒中風(fēng)險(xiǎn)增加10~17倍[6],血栓栓塞事件發(fā)生率可高達(dá)27.09%[11]。校正年齡、心功能分級(jí)、左心房大小及左心室射血分?jǐn)?shù)等影響因素后,房顫仍是HCM患者心力衰竭及卒中相關(guān)死亡的獨(dú)立危險(xiǎn)因素[6,9]。
表4 非計(jì)劃性心血管原因住院的單因素Cox分析
表5 非計(jì)劃性心血管原因住院的多因素Cox分析
因房顫可顯著增加HCM患者的不良心血管事件和非計(jì)劃住院率[12],維持竇性心律對(duì)HCM患者至關(guān)重要??剐穆墒СK幬镫m被推薦用于此類患者[13],但長(zhǎng)期療效有限且存在藥物相關(guān)不良反應(yīng)[3]。隨著導(dǎo)管消融技術(shù)的發(fā)展,越來越多的HCM合并房顫患者已接受導(dǎo)管消融治療。據(jù)報(bào)道,HCM合并房顫患者中,單次導(dǎo)管消融治療的竇性心律維持率在41.3%~66.1%[14],多次消融后可提升至47%~77%[15-17]。雖然圍術(shù)期主要不良事件的發(fā)生率與普通房顫人群并無差異[18],HCM合并房顫患者消融術(shù)后的竇性心律維持率仍相對(duì)較低[19],22%~48%患者需繼續(xù)接受藥物治療[15, 20]。推測(cè)其可能原因在于:(1)HCM患者的心肌細(xì)胞排列紊亂及心肌纖維化為折返性心律失常的發(fā)生提供了潛在基質(zhì)[21];(2)常規(guī)導(dǎo)管消融釋放的射頻能量難以穿透增厚的心房肌,產(chǎn)生的熱效應(yīng)不足,降低了導(dǎo)管消融治療的有效性[15]。本研究中,HCM合并房顫患者單次導(dǎo)管消融術(shù)后(17.6±8.4)個(gè)月的竇性心律維持率為66.7%,與既往研究在HCM患者中觀察到的結(jié)果相似。
盡管導(dǎo)管消融術(shù)后竇性心律維持率存在一定波動(dòng),導(dǎo)管消融治療仍可顯著改善HCM合并房顫患者的臨床預(yù)后。Bassiouny等[22]的研究中,HCM合并房顫者接受雙側(cè)肺靜脈前庭隔離后平均心功能分級(jí)(NYHA分級(jí))從2.17級(jí)改善至1.40級(jí)。在雙側(cè)肺靜脈隔離基礎(chǔ)上加行線性消融,患者的心功能可從(1.9±0.7)級(jí)恢復(fù)至(1.2±0.5)級(jí)[23]。與基線狀態(tài)相比,導(dǎo)管消融術(shù)后3個(gè)月和12個(gè)月,HCM患者的生活質(zhì)量也顯著提高[3]。此外,消融術(shù)后患者的房顫負(fù)荷亦明顯減少[22]。本研究中,導(dǎo)管消融組的非計(jì)劃性心血管原因住院率顯著低于藥物治療組,僅2例患者因快速心律失常發(fā)作住院治療,未見心力衰竭、卒中、外周動(dòng)脈栓塞等不良事件,同樣證實(shí)了導(dǎo)管消融治療的臨床獲益。
與以往研究不同的是,本研究對(duì)HCM合并房顫患者非計(jì)劃性心血管原因住院的影響因素進(jìn)行了探討,結(jié)果顯示,校正年齡、房顫類型和既往卒中病史后,房顫治療策略仍是非計(jì)劃性心血管原因住院的獨(dú)立危險(xiǎn)因素。導(dǎo)管消融組患者成功控制房顫后,房顫相關(guān)的心力衰竭、卒中及外周動(dòng)脈栓塞風(fēng)險(xiǎn)均顯著降低,非計(jì)劃性心血管原因住院事件相應(yīng)減少。
本研究雖為回顧性研究,但所有數(shù)據(jù)均為前瞻性收集,研究結(jié)果具有較好的準(zhǔn)確性。作為一項(xiàng)多中心研究,各家醫(yī)院采用的消融策略和隨訪周期長(zhǎng)短不盡相同,可能影響房顫消融的成功率。此外,隨訪過程中以標(biāo)準(zhǔn)12導(dǎo)聯(lián)心電圖和24 h動(dòng)態(tài)心電圖為主要檢測(cè)手段,可能低估了無癥狀性房顫的復(fù)發(fā)率。
綜上所述,本研究通過比較HCM合并房顫患者導(dǎo)管消融與藥物治療的臨床療效,首次證實(shí)了房顫治療策略為HCM合并房顫患者非計(jì)劃性心血管原因再住院的獨(dú)立危險(xiǎn)因素。這一發(fā)現(xiàn)為合理選擇治療策略,改善患者臨床預(yù)后提供了理論依據(jù)。
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The effect of catheter ablation and pharmacologic therapy on cardiac-related hospitalization in hypertrophic cardiomyopathy patients with atrial fibrillation
LI Jing-ye, DU Xin, LONG De-yong, JIANG Chen-xi, GUO Xue-yuan, ZHANG Ting, LI Xin, DONG Jian-zeng, MA Chang-sheng.
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
Correspoding author: MA Chang-sheng, Email: chshma@vip.sina.com
Objective To evaluate the effect of radiofrequency catheter ablation (RFCA) and pharmacologic therapy on cardiac-related hospitalization in hypertrophic cardiomyopathy (HCM) patients with atrial fibrillation (AF). Methods This study enrolled forty-eight HCM patients with AF who initially underwent catheter ablation. Seventy-eight subjects who only received pharmacologic therapy were selected as the control group. AF recurrence and cardiac-related hospitalization were followed-up routinely. Results After follow-up of 17.6±8.4 months, AF recurrence occurred in 16(33.3%) patients after a single procedure. In the control group, successful restoration of sinus rhythm was achieved in 39.7% patients after an average of 10.7±8.0 months. The unplanned cardiac-related hospitalization rate was significantly lower in the RFCA group (21.8%vs. 4.2%,P=0.0013). Cox regression analysis revealed that therapeutic strategy (HR9.082,95%CI1.130-73.011,P=0.038) and heart failure history (HR2.860,95%CI1.072-7.633,P=0.036) were independent risk factors of unplanned cardiac-related hospitalization. Conclusions In HCM patients with AF, catheter ablation seems to be superior to pharmacologic therapy in sinus rhythm maintenance and unplanned cardiac-related hospitalization reduction. Therapeutic strategy and heart failure history were independent risk factors of unplanned cardiac-related hospitalization.
Hypertrophic cardiomyopathy; Atrial fibrillation; Catheter ablation; Pharmacologic therapy; Cardiac-related hospitalization
10.3969/j.issn.1004-8812.2016.10.003
國家自然科學(xué)基金項(xiàng)目(81470464、81530016);北京市醫(yī)院管理局臨床醫(yī)學(xué)發(fā)展專項(xiàng)經(jīng)費(fèi)資助(ZYLX201302);科技部國際合作項(xiàng)目(2013DFB30310)
100029 北京,首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院心內(nèi)科
馬長(zhǎng)生,Email:chshma@vip.sina.com
R541
2016-06-20)