【摘要】目的 探討左心耳排空速度(LAAEV)對非瓣膜性心房顫動(NVAF)患者射頻導(dǎo)管消融(RFCA)術(shù)后晚期復(fù)發(fā)的臨床預(yù)測價值。方法 回顧性分析2020年1月—2023年5月在中國人民解放軍總醫(yī)院第一醫(yī)學(xué)中心心血管內(nèi)科入院并首次行RFCA的217例NVAF患者的臨床資料,通過術(shù)后門診復(fù)查、再次入院、電話等方式隨訪術(shù)后復(fù)發(fā)情況。根據(jù)RFCA術(shù)后3個月之后是否復(fù)發(fā),將研究對象分成復(fù)發(fā)組(64例)和未復(fù)發(fā)組(153例)。統(tǒng)計兩組患者一般資料并進(jìn)行組間比較,將差異有統(tǒng)計學(xué)意義的因素納入單因素和多因素logistic回歸模型進(jìn)一步分析,得出LAAEV是否為NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的獨(dú)立危險因素的結(jié)論,并根據(jù)ROC曲線及曲線下面積(AUC)分析該因素對RFCA術(shù)后晚期復(fù)發(fā)的預(yù)測價值。結(jié)果 復(fù)發(fā)組在持續(xù)性房顫、病程、N末端腦鈉肽前體、早期復(fù)發(fā)方面均高于未復(fù)發(fā)組,而LAAEV比未復(fù)發(fā)組低,差異有統(tǒng)計學(xué)意義(P<0.05),logistic回歸分析可見LAAEV與NVAF患者RFCA術(shù)后晚期復(fù)發(fā)獨(dú)立相關(guān)(P<0.05),ROC曲線顯示AUC為0.661,截斷值為0.348,靈敏度為68.8%,特異度為66.0%。結(jié)論 LAAEV是NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的一個獨(dú)立危險因素,且具有較顯著的預(yù)測價值。
【關(guān)鍵詞】非瓣膜性心房顫動;射頻導(dǎo)管消融;左心耳排空速度;晚期復(fù)發(fā)
【DOI】10.16806/j.cnki.issn.1004-3934.2024.12.016
The Prognostic Significance of Left Atrial Appendage Emptying Velocity in Predicting Late Recurrence After Radiofrequency Catheter Ablation in Patients with Nonvalvular Atrial Fibrillation
HU Yanmin1,LIU Saizhe2,ZHU Shenshen1,LIU Yang3,WU Zhaoke1
(1.Geriatric Medicine Department of The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,Henan,China;2.Cardiovascular Medicine Department of The First Medical Center of Chinese PLA General Hospital,Beijing 100039,China;3.Cardiovascular Medicine Department of The 989th Central Hospital of PLA,Luoyang 471000,Henan,China)
【Abstract】Objective To investigate the clinical predictive value of left atrial appendage emptying velocity (LAAEV) for late recurrence in patients with nonvalvular atrial fibrillation (NVAF) undergoing radiofrequency catheter ablation (RFCA).Methods Retrospective analysis of the clinical data of 217 patients with NVAF who presented to the
Cardiovascular Medicine Department of The First Medical Center of Chinese PLA General Hospital from January 2020 to May 2023 and underwent RFCA for the first time.The recurrence of NVAF after RFCA was followed up by outpatient review,re-hospitalization,and telephone call.According to whether recurred after 3 months,the subjects were divided into a recurrence group (64 cases) and a non-recurrence group (153 cases) .The general data of the two groups of patients were counted and compared between the two groups.The factors with statistically significant differences were included in the univariate and multivariate logistic regression models for further analysis to conclude whether LAAEV was an independent risk factor for late recurrence after RFCA in NVAF patients,and the predictive value of LAAEV in late recurrence after RFCA was analyzed according to ROC curve and AUC value.Results The levels of persistent atrial fibrillation,duration of disease,N-terminal pro-brain natriuretic peptide and early recurrence in the recurrent group were higher than those in the non-recurrent group,while LAAEV was lower than that in the non-recurrent group,and the differences were statistically significant (P<0.05).Logistic regression analysis showed that LAAEV was independently associated with late recurrence after RFCA in patients with NVAF (P<0.05).The ROC curve shows that the AUC is 0.661,the cutoff is 0.348,the sensitivity is 68.8%,and the specificity is 66.0%.Conclusion LAAEV is an independent risk factor for late recurrence after RFCA in NVAF patients,with significant predictive value.
【Keywords】Nonvalvular atrial fibrillation;Radiofrequency catheter ablation;Left atrial appendage emptying velocity;Late recurrence
非瓣膜性心房顫動(nonvalvular atrial fibrillation,NVAF)是臨床常見的心律失常,其特征是心房電活動紊亂,從而抑制正常竇性心律,影響全球約3 000萬人,其發(fā)病率和患病率在全球范圍內(nèi)均呈上升趨勢。根據(jù)《2023 ACC/AHA/ACCP/HRS心房顫動診斷及管理指南》[1](以下簡稱《指南》)分析,NVAF可導(dǎo)致多種不良結(jié)局的風(fēng)險增加,包括卒中風(fēng)險增加2.4倍,認(rèn)知障礙或癡呆風(fēng)險增加1.5倍,心肌梗死風(fēng)險增加1.5倍,心源性猝死風(fēng)險增加2倍,心力衰竭(heart failure,HF)風(fēng)險增加5倍,慢性腎臟病風(fēng)險增加1.6倍,外周動脈疾病風(fēng)險增加1.3倍。近年來,NVAF管理發(fā)生了變化,強(qiáng)調(diào)生活方式、危險因素調(diào)整和早期心律控制的重要性,特別是射頻導(dǎo)管消融(radiofrequency catheter ablation,RFCA)的作用[2]。近期試驗數(shù)據(jù)表明早期心律控制的凈臨床獲益超過心室率控制,全因死亡率顯著降低[3],預(yù)示著NVAF節(jié)律管理方法將發(fā)生巨大變化。
根據(jù)《指南》,NVAF節(jié)律控制的方法包括口服抗心律失常藥、直流電復(fù)律、RFCA或外科消融[1],目前RFCA為NVAF的一線治療手段。眾多研究[4]表明,RFCA成功率在過去幾十年中有所提高,但相關(guān)研究[5-6]顯示NVAF患者RFCA術(shù)后復(fù)發(fā)率為30%~50%。因此如何有效預(yù)防NVAF患者RFCA術(shù)后復(fù)發(fā)仍是NVAF規(guī)范診療進(jìn)展中一個亟待解決的問題,能有效識別相關(guān)危險因素,進(jìn)而辨別復(fù)發(fā)高風(fēng)險人群對預(yù)防復(fù)發(fā)是至關(guān)重要的[7]。有研究發(fā)現(xiàn),在臨床實(shí)踐中,RFCA術(shù)后3個月內(nèi)復(fù)發(fā)患者50%可自行轉(zhuǎn)復(fù)為竇性心律,無需再次手術(shù)治療[8],故對RFCA術(shù)后3個月之后復(fù)發(fā)(又稱晚期復(fù)發(fā))的研究更有臨床意義。
據(jù)研究,左心耳的體積和功能可能與NVAF患者RFCA術(shù)后復(fù)發(fā)有關(guān)[9],而左心耳排空速度(left atrial appendage emptying velocity,LAAEV)可評估左心耳功能,且LAAEV可通過經(jīng)食管超聲心動圖檢查(transesophageal echocardiography,TEE)測量,故推測LAAEV可能是預(yù)測NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的危險因素。本研究旨在探索初次接受RFCA手術(shù)的NVAF患者術(shù)前TEE測量的LAAEV與術(shù)后晚期復(fù)發(fā)之間的相關(guān)性,提供一種臨床評估方法來預(yù)測NVAF患者RFCA術(shù)后復(fù)發(fā)的風(fēng)險。
1 對象與方法
1.1 研究對象
選取2020年1月—2023年5月在中國人民解放軍總醫(yī)院第一醫(yī)學(xué)中心心血管內(nèi)科住院的罹患NVAF且行RFCA的患者為研究對象。本研究通過中國人民解放軍總醫(yī)院第一醫(yī)學(xué)中心倫理委員會審批(SQ202154)。
1.2 納入標(biāo)準(zhǔn)
(1)患者知曉并簽署知情同意書;(2)患者基本情況及臨床資料真實(shí)完整;(3)根據(jù)《指南》[1],符合NVAF診斷;(4)首次行RFCA術(shù);(5)術(shù)式為環(huán)肺靜脈隔離;(6)術(shù)后1個月、3個月、6個月、1年、2年、3年、4年完成門診隨訪且心電圖等資料完整者,或再入院且復(fù)查資料已完善者,或電話隨訪可網(wǎng)絡(luò)上傳術(shù)后心電圖情況者。
1.3 排除標(biāo)準(zhǔn)
(1)風(fēng)濕性心臟病或行心臟瓣膜手術(shù)的患者;(2)TEE發(fā)現(xiàn)左心房血栓或煙霧狀回聲的患者;(3)急性冠脈綜合征的患者;(4)肝功能不全(谷草轉(zhuǎn)氨酶或谷丙轉(zhuǎn)氨酶≥3倍正常值)的患者;(5)重度腎功能不全(腎小球濾過率≤30 mL/min)的患者;(6)甲狀腺功能亢進(jìn)的患者;(7)合并免疫系統(tǒng)疾病的患者;(8)妊娠或哺乳期女性;(9)術(shù)后至今失訪或臨床資料不完整的患者。
1.4 手術(shù)方法
(1)術(shù)前準(zhǔn)備:完善實(shí)驗室檢驗,包括血尿便常規(guī)和生化、凝血功能、甲狀腺功能,并行心電圖、超聲心動圖檢查,術(shù)前24 h內(nèi)行TEE,并簽署手術(shù)知情同意書。
(2)手術(shù)過程:患者取平臥位,消毒,鋪巾,右側(cè)腹股溝區(qū)局部麻醉,穿刺右側(cè)股靜脈,送入導(dǎo)絲、血管擴(kuò)張器及鞘管,拔出導(dǎo)絲及血管擴(kuò)張器,沿鞘管將電極送至冠狀竇,沿長導(dǎo)絲將長鞘送至上腔靜脈,撤出長導(dǎo)絲,將房間隔穿刺針?biāo)腿腴L鞘,透視下將長鞘回撤至房間隔,右前斜45°透視下穿刺房間隔成功。首劑靜脈注射肝素5 000 U,此后追加肝素1 000 U/h,連續(xù)3 h,行左右肺靜脈造影。將Pentaray電極導(dǎo)管送入左心房,在三維電解剖標(biāo)測系統(tǒng)指導(dǎo)下進(jìn)行左心房三維立體構(gòu)型及基質(zhì)標(biāo)測。退出Pentaray電極,送Smart Touch大頭消融導(dǎo)管至左心房,于雙側(cè)肺靜脈前庭線性消融,人工智能指導(dǎo)下應(yīng)用功率模式,兩側(cè)環(huán)肺靜脈消融后如患者未能轉(zhuǎn)復(fù)竇性心律,遂予以200 J直流電復(fù)律,轉(zhuǎn)復(fù)竇性心律,將大頭送入兩側(cè)肺靜脈內(nèi)顯示肺靜脈電位消失,高壓起搏未傳出,提示肺靜脈達(dá)到完全電隔離,達(dá)到手術(shù)終點(diǎn),拔出電極及鞘管,局部壓迫止血并加壓包扎。
1.5 術(shù)后管理
(1)藥物管理:根據(jù)CHA2DS2-VASc評分及術(shù)后復(fù)發(fā)情況,需口服華法林或新型口服抗凝藥物(達(dá)比加群酯/利伐沙班/艾多沙班)至少3個月;口服華法林的患者需維持國際標(biāo)準(zhǔn)化比值2~3;另需口服抗心律失常藥(普羅帕酮/胺碘酮/決奈達(dá)?。硞€月。(2)隨訪管理:術(shù)后1個月、3個月、6個月、1年、2年、3年、4年到??崎T診復(fù)查,出現(xiàn)不適及時就診。
1.6 數(shù)據(jù)收集
(1)患者的一般資料:包括住院身份識別號碼,體重指數(shù)(body mass index,BMI),NVAF類型,病程,吸煙史和飲酒史,有無高血壓、糖尿病、冠心病等病史。(2)患者住院時的生化指標(biāo):包括肌酐、尿酸、乳酸脫氫酶、低密度脂蛋白膽固醇、N末端腦鈉肽前體(N-terminal pro-brain natriuretic peptide,NT-proBNP)等。(3)術(shù)前的超聲心動圖、手術(shù)前后12或18導(dǎo)聯(lián)心電圖等結(jié)果。(4)TEE測量的LAAEV,方法為:使用配備有S5-1相控陣和X7-2t矩陣TEE換能器的iE33和Epiq7C系統(tǒng),在患者清醒平靜期間進(jìn)行TEE,從0°、45°、90°和135°四個視圖左心耳成像來檢測自發(fā)回聲對比。隨后,將樣品體積放置在左心耳的中間部分,并測量左心耳排空的峰值速度。(5)手術(shù)情況:包括術(shù)式、手術(shù)時長等。(6)藥物使用情況:包括華法林/達(dá)比加群酯/利伐沙班/艾多沙班等抗凝藥物,β受體阻滯劑、地高辛、普羅帕酮/胺碘酮/決奈達(dá)隆等抗心律失常藥。(7)隨訪情況:隨訪方法包括心血管內(nèi)科??漆t(yī)生門診隨訪、再入院心電圖檢查和電話隨訪,記錄心房顫動(房顫)有無復(fù)發(fā)、服藥情況及臨床結(jié)局事件。在研究中,NVAF患者RFCA術(shù)后復(fù)發(fā)定義為:RFCA術(shù)后行心電圖或動態(tài)心電圖,記錄到1次持續(xù)30 s以上的房性心律失常(房顫、心房撲動或房性心動過速),且術(shù)后3個月內(nèi)復(fù)發(fā)為早期復(fù)發(fā),3個月之后至隨訪結(jié)束復(fù)發(fā)為晚期復(fù)發(fā)。本研究隨訪時間為7~48個月,平均隨訪時間為(29.01±4.95)個月,其中復(fù)發(fā)組為(29.36±5.66)個月,未復(fù)發(fā)組為(28.87±0.71)個月。
1.7 統(tǒng)計學(xué)方法
應(yīng)用SPSS 27統(tǒng)計軟件,定量資料符合正態(tài)分布的用均值±標(biāo)準(zhǔn)差表示,采用t檢驗;不符合正態(tài)分布的以中位數(shù)及四分位數(shù)間距[M(Q1,Q3)]表示,采用非參數(shù)檢驗(Mann-Whitney U檢驗)。定性資料以例數(shù)及百分比(%)表示,采用χ2檢驗。采用單因素logistic分析,得到與NVAF患者RFCA術(shù)后晚期復(fù)發(fā)相關(guān)的因素,采用多因素logistic分析,得到其獨(dú)立危險因素。繪制ROC曲線并計算曲線下面積(area under the curve,AUC)值來評估預(yù)測價值,以P<0.05為差異有統(tǒng)計學(xué)意義。
2 結(jié)果
2.1 兩組患者一般資料對比
本研究共納入NVAF患者217例,其中男性162例(74.65%),女性55例(25.35%);持續(xù)性房顫患者73例(33.64%),陣發(fā)性房顫患者144例(66.36%);術(shù)后晚期復(fù)發(fā)患者64例,復(fù)發(fā)率約為29.49%。與之前相關(guān)研究一致。
分析可見,兩組患者在性別、年齡、BMI、高血壓、糖尿病、冠心病、吸煙史、飲酒史、肌酐、尿酸、乳酸脫氫酶、低密度脂蛋白膽固醇、左心房前后徑、左室射血分?jǐn)?shù)、服用華法林/達(dá)比加群酯/利伐沙班/艾多沙班、服用β受體阻滯劑、服用普羅帕酮/胺碘酮/決奈達(dá)隆、CHA2DS2-VASc評分上比較差異無統(tǒng)計學(xué)意義(P>0.05),而兩組在持續(xù)性房顫、病程、NT-proBNP、早期復(fù)發(fā)、LAAEV方面比較差異有統(tǒng)計學(xué)意義(P<0.05)。見表1。
2.2 單因素logistic回歸分析
根據(jù)表1結(jié)果,將持續(xù)性房顫、病程、NT-proBNP、早期復(fù)發(fā)、LAAEV逐一納入單因素logistic回歸分析,可見持續(xù)性房顫、早期復(fù)發(fā)、LAAEV對NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的影響均有統(tǒng)計學(xué)意義(P<0.05)。見表2。
2.3 多因素logistic回歸分析
將NVAF患者RFCA術(shù)后3個月后是否復(fù)發(fā)作為因變量,根據(jù)單因素分析結(jié)果,將P<0.1的因素包括持續(xù)性房顫、病程、早期復(fù)發(fā)、LAAEV均納入logistic回歸模型進(jìn)行分析,結(jié)果可見早期復(fù)發(fā)和LAAEV是NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的獨(dú)立危險因素(P<0.05)。見表3。
2.4 LAAEV對NVAF患者RFCA術(shù)后晚期復(fù)發(fā)的預(yù)測價值
ROC曲線顯示,LAAEV可預(yù)測NVAF患者RFCA術(shù)后晚期復(fù)發(fā),其AUC為0.661,95%CI為0.576~0.747,截斷值為0.348,此時靈敏度為68.8%,特異度為66.0%,P<0.001。見圖1。
2.5 臨床結(jié)局事件
記錄研究對象隨訪期臨床結(jié)局事件,包括卒中、體循環(huán)栓塞、HF、心血管死亡、非計劃再入院等。通過電話隨訪方式隨機(jī)對50例患者進(jìn)行二次隨訪,并收集了相關(guān)數(shù)據(jù)。其中復(fù)發(fā)組15例,未復(fù)發(fā)組35例,統(tǒng)計兩組臨床結(jié)局事件發(fā)生情況,復(fù)發(fā)組發(fā)生卒中1例(6.67%)、體循環(huán)栓塞0例、HF 2例(13.33%)、心血管死亡1例(6.67%)、非計劃再入院3例(20.00%);未復(fù)發(fā)組發(fā)生卒中2例(5.71%)、體循環(huán)栓塞0例、HF 2例(5.71%)、心血管死亡2例(5.71%)、非計劃再入院2例(5.71%),兩組比較差異無統(tǒng)計學(xué)意義(P>0.05)。
3 討論
NVAF患者中,大多數(shù)(80%~94%)的心律失常觸發(fā)源來自肺靜脈[10-11]。因此,肺靜脈電隔離是所有NVAF患者RFCA的基礎(chǔ)。然而,NVAF患者RFCA術(shù)后復(fù)發(fā)的主要原因之一是左心房-肺靜脈電連接恢復(fù),這與術(shù)前左心房組織重構(gòu)有關(guān)[12-14]。心房牽張、心肌缺血、自主神經(jīng)功能障礙、遺傳因素、肥胖和氧化應(yīng)激都可能改變心房的結(jié)構(gòu)和電生理特性[15]。據(jù)文獻(xiàn)[16-21]報道,持續(xù)性房顫、左心房擴(kuò)大、高血壓、糖尿病、年齡、肥胖、HF、慢性腎功能不全、術(shù)前胺碘酮失敗和左心耳大小是NVAF患者RFCA術(shù)后復(fù)發(fā)的獨(dú)立預(yù)測因素。然而,因數(shù)據(jù)存在爭議,既往研究的結(jié)論不一致。關(guān)于NVAF患者RFCA術(shù)后復(fù)發(fā)的影響因素仍然是臨床的一個研究熱點(diǎn)。由于大多數(shù)NVAF患者復(fù)發(fā)發(fā)生在初次手術(shù)后的3個月內(nèi),臨床稱為“空白期”,其發(fā)生通常與消融后炎癥和不均勻瘢痕組織形成有關(guān)[5]。本研究表明,早期復(fù)發(fā)與NVAF患者RFCA術(shù)后晚期復(fù)發(fā)有相關(guān)性,與某些研究[22]一致,但相關(guān)機(jī)制尚不明確。關(guān)于LAAEV的相關(guān)研究較少,本研究可為NVAF患者RFCA術(shù)后晚期復(fù)發(fā)增添一個新的預(yù)測因子。
眾所周知,NVAF易導(dǎo)致左心房血栓形成,且大多血栓形成局限于左心耳內(nèi)。在NVAF患者中,左心耳血流的特征是低速快速交替排空和充盈,缺乏有效的心房收縮,導(dǎo)致血液淤滯和促血栓形成的環(huán)境[23]。研究[24]表明,左心耳開口處血流速度≤0.55 m/s時,左心耳血栓形成的風(fēng)險增加;血流速度<0.37 m/s在預(yù)測卒中發(fā)生方面顯示出最高的準(zhǔn)確性。在LAAEV預(yù)測NVAF患者RFCA術(shù)后復(fù)發(fā)的機(jī)制方面,近期研究發(fā)現(xiàn),LAAEV與左心房電壓呈正相關(guān),與左心房體積呈負(fù)相關(guān)[25-26];慢性壓力超負(fù)荷導(dǎo)致左心房擴(kuò)大,而左心房功能受損先于左心房擴(kuò)大,作為反映左心房收縮和儲備功能的指標(biāo),LAAEV可提示左心房功能性重構(gòu)的嚴(yán)重程度,這可能發(fā)生在左心房重構(gòu)的早期階段[27]。因此,LAAEV是比左心房大小更敏感的預(yù)測NVAF患者RFCA術(shù)后復(fù)發(fā)的預(yù)測因素[28],且可能對NVAF患者RFCA術(shù)后臨床結(jié)局事件有一定預(yù)測價值。
本研究的意義在于,對LAAEV降低的NVAF患者而言,其在與醫(yī)生討論RFCA術(shù)后的預(yù)后時,可客觀預(yù)期手術(shù)的效果;臨床醫(yī)生可能會考慮延長LAAEV降低患者的抗心律失常治療時間,以改善RFCA術(shù)后的心律控制;對于未來的臨床研究,可探討在這一特定患者亞組中進(jìn)行除單獨(dú)肺靜脈隔離之外的其他消融的受益,以提供更積極的選擇。
本研究也存在一些局限性。本研究為小樣本、單中心回顧性隊列研究,這可能導(dǎo)致偏倚。復(fù)發(fā)病例收集方式僅通過心血管內(nèi)科專科醫(yī)生門診隨訪、再入院心電圖檢查和電話隨訪,未進(jìn)行連續(xù)心臟監(jiān)測,可能遺漏了無癥狀陣發(fā)性房顫RFCA術(shù)后復(fù)發(fā)的患者,從而低估了復(fù)發(fā)率。對臨床結(jié)局事件的收集樣本量小,不足以有力地反映LAAEV降低對NVAF患者RFCA術(shù)后臨床結(jié)局事件發(fā)生的影響,根據(jù)臨床需要后續(xù)可擴(kuò)大樣本量,補(bǔ)充研究。
總之,LAAEV降低與NVAF患者RFCA術(shù)后晚期復(fù)發(fā)明顯相關(guān),是一個獨(dú)立危險因素。
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收稿日期:2024-04-03