王玉占,劉 娟
心電圖參數(shù)預(yù)測心臟再同步治療患者發(fā)生超反應(yīng)的意義
王玉占,劉 娟
目的 探討12導(dǎo)聯(lián)心電圖(ECG)參數(shù)預(yù)測心臟再同步治療患者發(fā)生超反應(yīng)的意義。 方法 采用ECG記錄心臟再同步治療(CRT)設(shè)備植入前基線水平及植入后即刻心電活動,分析基線ECG參數(shù)(QRS波時限、束支形態(tài)、電軸、PQ間期、QT間期)及植入后起搏QRS時限,并計(jì)算QRS時限的相對變化。超反應(yīng)定義為12個月后左室舒張末期容積降低≥30%。結(jié)果 本組101例患者,32例(31.7%)出現(xiàn)超反應(yīng)。超反應(yīng)組與非超反應(yīng)組之間ECG基線水平差異無統(tǒng)計(jì)學(xué)意義,但超反應(yīng)組起搏QRS時限短于非超反應(yīng)組[(148±22)msvs(162±28)ms;P=0.010]。CRT植入后超反應(yīng)組出現(xiàn)QRS波顯著降低。超反應(yīng)組出現(xiàn)相對QRS波縮短的比例顯著高于非超反應(yīng)組[12.1%(6.8~22.2)vs1.7%(-11.9~11.8);P=0.005]。采用多變量分析得出,NYHAⅡ級、起搏QRS時限及相對QRS波縮短是預(yù)測CRT患者發(fā)生超反應(yīng)的因素。 結(jié)論 起搏QRS時限及相對QRS波縮短是與CRT患者發(fā)生超反應(yīng)相關(guān)的參數(shù)。
心臟再同步治療(CRT);心電圖;超反應(yīng)
不管是心臟再同步治療(CRT)?起搏(CRT?P)或CRT?除顫(CRT?D),CRT都能夠改善頑固性心衰患者的癥狀、提高運(yùn)動量、引起左心室重構(gòu)逆轉(zhuǎn),從而降低心衰患者住院率和死亡率[1?3]。目前,一些多中心隨機(jī)研究已證實(shí),CRT治療可以改善超聲心動圖征象,其CRT反應(yīng)指左心室收縮末容積(LVESV)下降≥15%[4]。然而,由于CRT的反應(yīng)個體間存在著顯著差異,有些患者臨床癥狀改善顯著,左室完全逆轉(zhuǎn)重構(gòu),左室功能幾乎正常,這在臨床上稱為“CRT超反應(yīng)”[5]。鑒于超聲心動圖參數(shù)不具同步性,其預(yù)測CRT反應(yīng)性較差[6]。與此相反,研究表明QRS時限及形態(tài)學(xué)與CRT治療預(yù)后緊密相關(guān)[7]。本研究通過檢測CRT超反應(yīng)者的心電圖(ECG)參數(shù),探討其預(yù)測CRT超反應(yīng)的臨床價值。
1.1 一般資料 收集我院2013年1月至2015年6月接受CRT的慢性充血性心力衰竭(CHF)患者。入選標(biāo)準(zhǔn):12導(dǎo)聯(lián)心電圖QRS波時限≥120 ms,紐約心功能分級(NYHA)Ⅱ~Ⅳ級,左心室射血分?jǐn)?shù)(LVEF)<35%,最佳藥物治療基礎(chǔ),竇性心律。排除標(biāo)準(zhǔn):瓣膜病,最近3個月曾接受冠狀動脈支架植入術(shù)或搭橋術(shù),肝腎功能不全。分組:隨訪期間完善詳盡的臨床評估、ECG以及心超,根據(jù)CRT術(shù)后1年LVEF增加情況分為,研究組(超反應(yīng)組):LVEF≥30%以及對照組(無反應(yīng)組及有反應(yīng)組):增加<5%及LVEF增加≥5%但LVEF<30%為CRT(CRT?R)。
1.2 CRT植入 鎖骨下靜脈穿刺成功后,制作囊袋,采用冠狀靜脈引導(dǎo)系統(tǒng),定位冠狀竇開口,應(yīng)用靜脈球囊導(dǎo)管行冠狀靜脈造影,顯示心臟靜脈后,將左心室心外膜電極導(dǎo)線送至心臟靜脈的側(cè)支(心臟側(cè)靜脈或側(cè)后靜脈)。測試左室起搏奪獲的最滿意參數(shù)后,再分別植入右心房電極導(dǎo)線于右心耳及右心室電極導(dǎo)線于右心室心尖部,固定電極導(dǎo)線后連接雙室脈沖發(fā)生器,將起搏器埋藏于皮下囊袋中,縫合皮膚。
1.3 超聲心動圖 所有患者均在入院及CRT植入術(shù)后12個月行超聲檢查。采用GE Vivid 7超聲診斷儀,M4S探頭,頻率為1.5~4.3 MHz;分別采集胸骨旁左心室長軸切面、左心室二尖瓣、乳頭肌和心尖短軸切面及心尖四腔心、二腔心和三腔心切面3個心動周期二維和彩色多普勒圖像進(jìn)行測量,測量指標(biāo):左心室舒張末容積(LVEDV)、左心室收縮末容積(LVESV)及LVEF。
1.4 12導(dǎo)聯(lián)心電圖 患者取仰臥位,在雙心室起搏器植入前及植入后即刻進(jìn)行12導(dǎo)聯(lián)ECG測量。測量結(jié)果均有本研究之外的兩名心電圖專業(yè)醫(yī)師收集及分析,其主要包括:心率(HR)、QRS時限及電軸、PR及QTc間期。如果兩者出現(xiàn)分歧,則重復(fù)測量直至結(jié)果達(dá)成統(tǒng)一。①左束支傳導(dǎo)阻滯(LBBB)傳統(tǒng)定義為符合以下三條標(biāo)準(zhǔn)中任意一條:V1導(dǎo)聯(lián)呈QS或rS型,QRS時限≥120 ms,I、V6呈單向R波,前無Q波。②相對QRS時限變化定義為:QRSCRT-QRS基線/QRS基線(%),其中,負(fù)值表示相對QRS時限縮短。
1.5 統(tǒng)計(jì)學(xué)分析 所有數(shù)據(jù)采用SPSS 21.0軟件包進(jìn)行分析。采用柯爾莫諾夫?斯米爾諾夫檢驗(yàn)來分析變量是否符合某種分布。正態(tài)分布連續(xù)變量以均數(shù)±標(biāo)準(zhǔn)差表示,比較采用t檢驗(yàn)。非正態(tài)分布連續(xù)變量以中位數(shù)(四分位間距)表示,比較采用Wilcoxon符號秩和檢驗(yàn)或Mann?Whitney U檢驗(yàn)。分類變量以頻率及百分比表示,比較采用卡方檢驗(yàn)或Fisher精確檢驗(yàn)。超反應(yīng)預(yù)測因素采用單變量及多變量邏輯回歸分析。將單變量分析中P<0.2變量納入前進(jìn)逐步回歸程序。通過多變量邏輯回歸分析獲得最佳模型,把影響超反應(yīng)的最佳獨(dú)立變量設(shè)為獨(dú)立變量。計(jì)算超反應(yīng)比值比(OR)以及95%可信區(qū)間。采用受試者工作特征曲線(ROC)確定QRS時限變量預(yù)測CRT超反應(yīng)最佳界限值。以雙側(cè)P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。
2.1 研究對象特征 本研究納入101例合格患者,平均年齡(63.2±10.9)歲,其中男性占65.2%。缺血性心肌病37例(36.6%)。多數(shù)患者NYHA評分為Ⅲ(77例;76.2%)。LVEF中位值25%(20.0~30.0)。所有患者均為竇性心律?;€ECG特征及其他臨床表現(xiàn)見表1??诜幬铮?9例服用ACEI或血管緊張素Ⅱ受體阻滯劑,100例服用β受體阻滯劑,90例服用螺內(nèi)酯,70例使用利尿劑。
表1 超反應(yīng)組及非超反應(yīng)組基線特征及比較
2.2 超反應(yīng)組及非超反應(yīng)組臨床表現(xiàn)、ECG及心超特征 雙心室起搏植入后12個月,32例患者符合心超診斷超反應(yīng)的標(biāo)準(zhǔn)。15例患者LVESV降低15%~29%,54例患者LVESV沒有顯著降低(0%~14%),部分甚至升高。超反應(yīng)與非超反應(yīng)組臨床表現(xiàn)及基線心超參數(shù)比較見表1。超反應(yīng)組植入前腦鈉肽(BNP)顯著低于非超反應(yīng)組,兩組在其余心超參數(shù)、臨床表現(xiàn)及心衰藥物治療上差異無統(tǒng)計(jì)學(xué)意義。兩組植入前LVESV見表1,植入后,超反應(yīng)組LVESV(94.2±34.7)mL,而非超反應(yīng)組為(194.1±70.1)mL。兩組左心室電極位置(多位于側(cè)后靜脈)及無起搏方式顯著差異(P=0.127)。超反應(yīng)與非超反應(yīng)組基線心率、PR間期、QRS時限、QRS軸及QTc間期差異均無統(tǒng)計(jì)學(xué)意義。兩組患者QRS形態(tài)學(xué)無顯著差異,且LBBB出現(xiàn)QRS切跡比例亦無顯著差異[25(78.1%)vs 42(60.9%);P=0.088]。超反應(yīng)組在植入后QRS時限短于非超反應(yīng)組[(148± 22)ms vs(162±28)ms;P=0.010],與植入前相比,QRS時限顯著降低[(167±26)ms降至(148±22)ms;P=0.010],而非超反應(yīng)組則無顯著降低[(165±27)ms到(162±28)ms;P=0.536]。超反應(yīng)組QRS波形相對縮短比例顯著高于非超反應(yīng)組[12.1%(6.8~22.2)vs 1.7%(-11.9~11.8);P=0.005]。
2.3 預(yù)測CRT超反應(yīng) 單變量分析得出,與超反應(yīng)相關(guān)的變量包括NYHA分級、QRS時限及相對縮短的QRS波。將單因素分析中P<0.2變量(NYHA分級、正常軸、LBBB出現(xiàn)切跡、植入后QRS時限、相對QRS縮短)采用多變量邏輯回歸模式進(jìn)行校正,得出QRS時限與QRS縮短與CRT超反應(yīng)獨(dú)立相關(guān)。見表2。為進(jìn)一步明確QRS時間參數(shù)預(yù)測CRT超反應(yīng)的最佳界值,采用ROC曲線分析。相對QRS縮短預(yù)測超反應(yīng)的曲線(AUC=0.68,95%CI 0.57~0.78),相對QRS縮短預(yù)測CRT超反應(yīng)界值>4.5%,其敏感性及特異性分別為81%、58%。見圖1。
表2 單因素及多因素回歸模型預(yù)測CRT超反應(yīng)
圖1 相對QRS時限縮短預(yù)測CRT超反應(yīng)ROC曲線
已有研究證實(shí),CRT治療可使心衰患者心超表現(xiàn)得以改善[8]。但臨床中也發(fā)現(xiàn),不同患者個體對CRT反應(yīng)的程度差異較大,部分患者出現(xiàn)CRT超反應(yīng)[9]。目前關(guān)于 CRT超反應(yīng)的定義無同一標(biāo)準(zhǔn)。由于對超反應(yīng)的定義不同,相應(yīng)研究報(bào)道的超反應(yīng)患者比例亦不盡相同(13%~38%)[10?11]。CRT治療后LVESV減小反應(yīng)LV結(jié)構(gòu)逆重構(gòu),其是預(yù)測CRT長期預(yù)后的重要因素[12?13],結(jié)合文獻(xiàn)報(bào)道,我們定義LVESV降低≥30%為CRT超反應(yīng)。本研究發(fā)生CRT超反應(yīng)患者比例(31.7%)與采用相同定義的研究基本一致。此外,各項(xiàng)研究間CRT后隨訪時間范圍廣(2個月到12個月)[14?15],CRT治療后,LV逆重構(gòu)至少需要9個月的時間[16],過早隨訪可能會導(dǎo)致出現(xiàn)超反應(yīng)數(shù)目較實(shí)際減少,從而造成結(jié)果差異。同樣,超反應(yīng)定義的不同也會導(dǎo)致超反應(yīng)預(yù)測因素的多樣化。先前有研究發(fā)現(xiàn),CRT植入前一些臨床特征及心超參數(shù)對于預(yù)測CRT超反應(yīng)有一定的意義,如女性、非缺血性心肌病、低BNP水平、基線LV直徑短及心室機(jī)械不同步[17]。雖然本研究結(jié)果也發(fā)現(xiàn),超反應(yīng)組具有較低的BNP水平以及NYHA分級,但其他基線臨床特征及心超特征與非超反應(yīng)組比較均無顯著差異。
CRT通過改變心電活動的順序從而改善左心室機(jī)械功能[18],因此,CRT可以說是一種“電活動”治療。心超通過檢測二尖瓣反流程度和左心室舒張模式,可為臨床選擇CRT適應(yīng)證提供的信息[19],但其不能同步反應(yīng)心電活動制約了預(yù)測CRT反應(yīng)性,而ECG參數(shù)可以表現(xiàn)心電活動紊亂及改善的狀態(tài),從這點(diǎn)來看,這應(yīng)該是預(yù)測CRT反應(yīng)的良好預(yù)測工具。雖然諸多研究證實(shí),CRT后QRS時限及QRS時限縮短與心臟重構(gòu)的總體改善存在顯著相關(guān),但其研究沒有涉及超反應(yīng)。本研究中,我們得出植入后QRS時限與相對QRS時限縮短是預(yù)測超反應(yīng)的獨(dú)立因素。相對QRS縮短預(yù)測CRT超反應(yīng)界值>4.5%,其敏感性及特異性分別為81%、58%。
目前,基線QRS時限對CRT超反應(yīng)的預(yù)測價值也存在差異,本研究得出,寬大的QRS波群對于CRT超反應(yīng)無預(yù)測價值,此結(jié)論與相關(guān)研究[20?21]結(jié)果一致,但也有些研究則認(rèn)為,寬大的QRS波群可降低臨床事件及CRT超反應(yīng)[22],其差異原因考慮與本研究組中QRS波群相對更寬(平均165 ms)。
根據(jù)心臟電?機(jī)械活動紊亂的病生學(xué)機(jī)制,CRT后引起的QRS時限的變化反應(yīng)了再同步的質(zhì)量,且可以間接的反應(yīng)心臟電?機(jī)械紊亂的修復(fù)程度[23]。QRS明顯縮短表明心肌基質(zhì)與LV起搏電極的位置高度同步[24?25]。如果起搏位置不佳會導(dǎo)致傳導(dǎo)緩慢,從而造成一個寬大的起搏QRS波群。Molhoek等[26]認(rèn)為,植入后即刻及半年后QRS時限縮短可以預(yù)測CRT反應(yīng)性。另外,Lecoq等[27]報(bào)道了類似結(jié)果,他們通過調(diào)整導(dǎo)絲位置以獲得最短的QRS時限,并最終發(fā)現(xiàn)QRS縮短是預(yù)測CRT反應(yīng)性的唯一因素,且對于早期預(yù)測CRT反應(yīng),QRS縮短是較易獲得的 ECG參數(shù)。Rickard等[21]采用多因素分析得出,QRS時限差值與心臟重構(gòu)顯著相關(guān),但是,ROC曲線未能進(jìn)一步證實(shí)其具有良好的特異性和敏感性。由于QRS時限縮短絕對值因個體差異,并受基線QRS時限的影響,因此其預(yù)測意義受到影響。我們認(rèn)為,就預(yù)測CRT反應(yīng)性而言,相對QRS時限縮短優(yōu)于絕對值。因此,通過檢測細(xì)微的QRS時限縮短也可能辨別出那些存在潛在預(yù)后不良的患者,相應(yīng)的對這些患者進(jìn)行密切監(jiān)護(hù)及增加治療干預(yù)(正性肌力藥物及抗心律失常藥物、CRT優(yōu)化等)可能會提高預(yù)后。
另外,本研究采用多因素模型分析后得出,除了ECG參數(shù)之外,NYHA分級也是預(yù)測超反應(yīng)的獨(dú)立因素,此結(jié)果與van Bommel等[28]研究一致,他們發(fā)現(xiàn)輕度HF患者(NYHA分級低)易發(fā)生CRT超反應(yīng)。2012年最新指南關(guān)于CRT適應(yīng)證較2008版寬泛,早期的研究由于當(dāng)時治療指南的局限性,它們排除了 NYHAⅡ患者。另一方面,有研究表明[29],LBBB形態(tài)不僅與臨床不良事件有關(guān),還是預(yù)測CRT超反應(yīng)的重要指標(biāo)。但本研究沒有得出相似結(jié)果,此差異考慮與本研究中LBBB人數(shù)多有關(guān),本研究約70%患者有LBBB。
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Electrocardiographic parameters predict super?response in cardiac resynchronization therapy
WANG Yu?zhan,LIU Juan
(Department of Clinical Electrophysiology,Ha Li Xun International Peace Hospital,Hengshui053000,Hebei,China)
Objective The aim of the study was to assess the value of ECG parameters to predict super?response in CRT pa?tients. Methods A 12?lead surface ECG was recorded at baseline and immediately after CRT?device implantation.Baseline ECG pa?rameters(QRS duration,bundle branch morphology,axis,PR interval,QTc)and post?implant paced QRS duration were analyzed;relative change in QRS duration was calculated.Decrease of left ventricular end?systolic volume≥30%after 12 months was classified as super?response. Results In group of 101 patients,32(31.7%)were super?responders.There were no significant differences in baseline ECG parameters between super?responders and other patients.Post?implant QRS duration was shorter in super?responders[(148±22)msvs(162±28)ms;P=0.010).Only in super?responders was significant QRS reduction observed after implantation.Rela?tive QRS shortening was higher in super?responders[12.1% (6.8 to 22.2)vs1.7% (-11.9 to 11.8);P=0.005].In a multivariable a?nalysis NYHA,post?implant QRS duration and relative QRS shortening remained independent predictor of super?response. Conclusion Post?implant QRS duration and relative QRS shortening are the only ECG parameters associated with super?response in CRT.
Cardiac resynchronization therapy(CRT);Electrocardiographic;Super?response
R541.6
A
1672?271X(2017)01?0062?05
10.3969/j.issn.1672?271X.2017.01.017
2016?07?14;
2016?11?29)
(本文編輯:葉華珍; 英文編輯:王建東)
053000衡水,哈勵遜國際和平醫(yī)院臨床電生理科
王玉占,劉 娟.心電圖參數(shù)預(yù)測心臟再同步治療患者發(fā)生超反應(yīng)的意義[J].東南國防醫(yī)藥,2017,19(1):62?66.