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      經導管主動脈瓣植入術后的起搏器植入

      2016-02-21 00:27:34詹智管麗華綜述
      心血管病學進展 2016年5期
      關鍵詞:主動脈瓣起搏器指征

      詹智 管麗華 綜述

      (復旦大學附屬中山醫(yī)院心血管內科,上海200032)

      ?

      經導管主動脈瓣植入術后的起搏器植入

      詹智 管麗華 綜述

      (復旦大學附屬中山醫(yī)院心血管內科,上海200032)

      從2002年經導管主動脈瓣植入術(transcatheter aortic valve implantation/replacement,TAVI/TAVR)第一次被運用到臨床[1],由于其顯著的收益/風險比,TAVI每年的手術數(shù)量在全球各大心臟中心呈井噴式增長。然而,TAVI手術并發(fā)癥是不可避免的問題,主要有心臟傳導阻滯、瓣周漏、主動脈瓣反流、血管并發(fā)癥、腎功能衰竭等。這其中TAVI術后心臟傳導阻滯并永久起搏器植入(permanent pacemaker implantation,PPI)是TAVI術后首要并發(fā)癥[2]。在解剖結構上,由于主動脈瓣靠近心臟傳導系統(tǒng),尤其是希氏束和左束支,所以在手術操作中瓣膜支架、導絲、輸送系統(tǒng)等,都可能對傳導系統(tǒng)造成擠壓損傷,從而引起傳導阻滯[3]。傳導功能障礙的主要類型為左束支傳導阻滯(left bundle branch block,LBBB)和房室傳導阻滯(atrio-ventricular block,AVB)。LBBB最終也可能會進展為高度或完全AVB[3]。不論是外科手術還是介入治療,當出現(xiàn)心臟傳導阻滯時,最重要的處理方法即安裝永久心臟起搏器(permanent pacemaker,PPM)。 Kogan等[4]研究發(fā)現(xiàn),與外科手術主動脈瓣植入術相比,TAVI術后PPM的植入率已經有了明顯的下降。

      多個注冊臨床試驗報道的TAVI術后PPM植入率不盡相同,GERY臨床試驗為33.7%[CoreValve(Medtronic Inc,Minneapolis,Minnesota,USA)為38.6%、Edwards SAPIEN(Edwards Lifesciences,Irvine,California,USA)為14.2%][5- 6],UK TAVI臨床試驗為16.3%(CoreValve為24.4%、Edwards SAPIEN為7.4%)[7],F(xiàn)RANCE2 臨床試驗為15.6%(CoreValve為24.2%、Edwards SAPIEN為11.5%)[8],Belgian臨床試驗為13%(CoreValve為22%、Edwards SAPIEN為5%)[9]。不同研究之間TAVI術后PPM植入率有很大差異,這與其影響因素眾多有很大關系。瓣膜類型、術前或術后擴張、瓣膜釋放深度、主動脈鈣化、室間隔肥厚等,都與傳導阻滯的發(fā)生率有關。另外,不同中心對于TAVI術后PPM植入指征的把握,也是PPM植入率不同的重要因素。

      現(xiàn)就TAVI術后的PPI做一篇綜述,通過綜合整理國內外的研究進展,促進對該領域的進一步認識和研究。

      1 TAVI術后PPM植入的預測因素

      盡管對于術后新發(fā)LBBB是否應該植入PPM沒有統(tǒng)一的共識,且有研究表明術后持續(xù)性LBBB對于30 d或1年的全因死亡率、心源性死亡、心力衰竭入院率并無影響,但短期內起搏器的植入率更高(主要因進展為高度AVB)[10]。所以將引起LBBB、高度AVB的預測因素與PPM植入的預測因素一并討論,以便更加全面的認識。

      1.1 瓣膜的選擇

      1.1.1 瓣膜的類型

      目前運用于臨床的瓣膜主要有CoreValve System、Edwards SAPIEN以及在歐洲運用較廣泛的Direct Flow Medical(DFM,Santa Rosa,CA,USA)瓣膜系統(tǒng)。在多個研究中均得到這樣一個結論,即與球囊膨脹的Edwards SAPIEN相比,自膨脹的CoreValve術后新發(fā)LBBB和PPM植入的概率更高[3,11-14]。其中,頭對頭的隨機臨床試驗CHOICE的數(shù)據(jù)顯示,CoreValve系統(tǒng)術后PPM植入率為37.6%,而Edwards SAPIEN瓣膜系統(tǒng)則為17.3%,且差異有顯著意義[14]。甚至有學者認為CoreValve系統(tǒng)的使用是發(fā)生傳導阻滯最重要的相關因素,這可能與CoreValve系統(tǒng)框架更長,植入的位置更深有關[3]。

      另外,研究也發(fā)現(xiàn)不同類型的瓣膜對傳導功能障礙持續(xù)時間的影響也有著顯著差異。在使用Edwards SAPIEN瓣膜系統(tǒng)的患者中,超過半數(shù)的傳導功能障礙會在術后幾天至幾個月內消失[13,15-16]。而使用CoreValve瓣膜系統(tǒng)的大多數(shù)患者,傳導功能障礙會一直持續(xù)到出院,直至1年的隨訪時間[17]。

      在隨機臨床試驗FRANCE2中,研究人員將第三代CoreValve瓣膜(即CoreValve Accutrak)與老一代的CoreValve瓣膜對比發(fā)現(xiàn),雖然前者對其輸送系統(tǒng)做了改進,但并未減少TAVI術后PPM的植入率和全因死亡率[18]。不過也有研究得出的結論截然相反,即新一代 CoreValve Accutrak能減少瓣膜植入深度,并因此降低新發(fā)LBBB的發(fā)生率和PPM植入率[19-20]。

      盡管關于兩種瓣膜系統(tǒng)孰優(yōu)孰劣還有爭議,但隨著操作經驗的不斷積累和輸送系統(tǒng)的不斷更新?lián)Q代,兩種瓣膜系統(tǒng)引起傳導功能異常較之前都有了顯著的下降[3,21]。減少瓣膜框架周圍組織的接觸損傷和可回收功能是目前瓣膜研究中最大的挑戰(zhàn)。一些新的瓣膜已經實現(xiàn)重新定位釋放的功能,例如DFM瓣膜和Lotus瓣膜(Sadra Medical Inc,Los Gatos,CA,USA)等[22-24]。在歐洲實行的DISVOVER (Evaluation of the Direct Flow Medical Percutaneous Aortic Valve 18F System for the Treatment of Patients with Severe Aortic Stenosis)試驗對DFM瓣膜系統(tǒng)的臨床應用進行了一個前瞻性、非隨機、多中心的研究,結果顯示其術后PPM的植入率為21%[25];但是,由于DFM瓣膜對比第一代瓣膜系統(tǒng)顯著減少了術后主動脈瓣反流和對比劑誘發(fā)的腎損傷,因此越來越受到心臟專家的青睞[26]。

      1.1.2 瓣膜釋放位置

      TAVI瓣膜由于在解剖位置上與傳導系統(tǒng)有著特殊的解剖位置關系,所以當瓣膜植入左室流出道的位置越深時,對傳導系統(tǒng)造成的損傷和影響越大,發(fā)生LBBB或完全AVB的概率也就越高[27-28]。不論是對于CoreValve瓣膜還是Edwards SAPIEN瓣膜,瓣膜植入的位置均被認為是TAVI術后新發(fā)LBBB的重要預測因素[13,17,29]。

      1.2 患者臨床特點

      Egger等[30]發(fā)現(xiàn),在使用CoreValve系統(tǒng)的患者中,若在TAVI術前或術中發(fā)生束支傳導阻滯,則有超過半數(shù)可能進展為高度AVB。Urena等[15]則發(fā)現(xiàn)TAVI術后新發(fā)LBBB的患者中超過1/3為暫時的。另外,與術前存在的LBBB相比,術前存在右束支傳導阻滯的患者術后PPM植入率更高,且被認為是PPI最重要的預測因素之一[31-33]。Mouillet等[34]認為術后即刻的QRS波周期是PPI重要的獨立預測因子,若患者術后即刻心電圖的QRS波周期≤128 ms,則基本沒有PPI的需要。

      另外,男性、無瓣膜手術史、主動脈鈣化、二尖瓣鈣化、室間隔厚度等均被認為可能是TAVI術后PPI預測因素[5,33,35]。

      1.3 術者的經驗

      由于心臟傳導系統(tǒng)解剖結構的復雜性,從球囊成形到生物瓣膜的膨脹、釋放,再到導絲、導管的移除,TAVI術中幾乎每個操作都會對傳導系統(tǒng)造成影響。在對多名患者TAVI術中持續(xù)心電監(jiān)測的結果進行回顧后,發(fā)現(xiàn)傳導異常首次發(fā)生在球囊擴張后占40%,CoreValve瓣膜系統(tǒng)膨脹后占33%,CoreValve瓣膜釋放到左室流出道后占12%,導管移除后占6%,導絲經過主動脈瓣時占4%[36]。所以術者對于心臟解剖結構的認識、手術操作熟練程度以及對于傳導阻滯的早期識別均直接影響了TAVI術后傳導阻滯的發(fā)生和PPM的植入。

      上述的種種預測因素證據(jù)大多來自小型隊列試驗、meta分析和描述性研究,仍需要大型隨機臨床試驗的進一步驗證。目前在臨床上,要根據(jù)個體化原則對患者進行綜合評估,做出最有利于患者預后的治療決策。

      2 植入指征

      2.1 植入指征

      目前就TAVI術后起搏器植入的指征尚無統(tǒng)一共識[37],普遍認可的指征有高度AVB(莫氏Ⅱ型或者更高度AVB)、新發(fā)LBBB(伴或不伴長PR間期)。

      2.1.1 新發(fā)LBBB(伴或不伴PR間期延長)的植入指征

      關于LBBB術后起搏器的植入一直存在爭議,也是研究的熱點課題。一方面,Urena等[15]發(fā)現(xiàn),在運用球囊擴張瓣膜系統(tǒng)的TAVI術后患者中,若術后出現(xiàn)LBBB則發(fā)生完全AVB的風險也相對較高。另外有研究認為,術后新發(fā)LBBB,尤其伴QRS延長的LBBB是TAVI術后全因死亡的重要獨立風險因子,這可能與心臟不同步性收縮有關[38-39]。另一方面,Ramazzina等[40]對TAVI術后PPM植入的患者進行了隨訪,發(fā)現(xiàn)約1/3的患者真正需要起搏器的心室起搏,且所有需要起搏的患者均為高度AVB患者。Boerlage-Van等[33]則發(fā)現(xiàn)約1/5術后新發(fā)的LBBB是暫時的,PPM植入的患者中1/5只有短期心臟起搏的必要。

      綜上,TAVI術后出現(xiàn)LBBB是否需要植入PPM沒有統(tǒng)一共識,PPM植入很大程度取決于研究人員或激進或保守的治療策略,這也是造成了各研究之間PPM植入率巨大差別的重要因素[3,13,40-41]。

      2.1.2 AVB的植入指征

      研究數(shù)據(jù)顯示TAVI術后發(fā)生高度AVB的患者中,約17%的患者可以緩解,并且沒有明確的緩解預測因子[40]。因此,一般認為TAVI術后出現(xiàn)Ⅱ度或Ⅲ度AVB是PPM植入的指征。

      3 植入時機

      一般在TAVI術后,會常規(guī)植入臨時起搏器。若患者在48~72 h監(jiān)測中沒有出現(xiàn)傳導障礙,則在移除起搏器后繼續(xù)遙測心電監(jiān)護數(shù)天。研究發(fā)現(xiàn),由于高度或完全傳導阻滯,在TAVI術后24 h和48 h植入起搏器的概率分別為33%和50%[42-43],這與目前歐洲推薦的標準相矛盾。后者建議對TAVI術后出現(xiàn)高度或完全AVB的患者,進行為期7 d的臨床觀察和心電監(jiān)護,在明確傳導功能障礙為暫時性還是永久性后,再決定是否植入PPM(ⅠC級證據(jù)),僅當出現(xiàn)完全AVB伴脫逸心律時可以結束觀察并植入PPM[38]。

      Egger等[30]對術前或術中發(fā)生束支傳導阻滯的患者預防性植入PPM和心腔內心電監(jiān)護,發(fā)現(xiàn)近半數(shù)后來發(fā)展為高度AVB的患者首次記錄的發(fā)病時間在出院后(平均住院天數(shù)13 d)。最近一段時間,對于出院后PPI的必要性也不斷被報道[44-46]。另一方面,Pereira等[35]的研究則認為PPI對于出院患者不是必要的。Simms等[47]也認為隨著時間推移,患者對于起搏器的依賴性也是不斷下降的。

      延長術后監(jiān)測時間固然是安全也是合理的,但無疑增加了患者住院天數(shù)和費用。除了進一步臨床隨機試驗的驗證外,根據(jù)每個患者術前臨床解剖特點和術中傳導系統(tǒng)損傷情況,制定相應的監(jiān)測周期和植入時機可能是最佳的處理方法。

      4 預后

      Dizon等[48]將PARTNER試驗中行TAVI手術的患者分為4組,分別為術前已安裝起搏器組、術后新植入起搏器組、LBBB/無起搏器組和無起搏器組。在對患者的1年隨訪中,研究人員發(fā)現(xiàn):前3組的全因死亡率高于無起搏器組,且臨床、結局更差,進一步數(shù)據(jù)分析得出起搏器為TAVI術后1年病死率的獨立危險因素。van der Boon等[11]認為,心室起搏誘導的房室和心室間的不協(xié)調工作形成了醫(yī)源性LBBB,從而影響心室充盈每搏量和心排血量,是起搏器影響患者預后的重要機制。然而,Gensas等[49]在另一個為期5年的隨訪中發(fā)現(xiàn),TAVI術后PPM植入組和非植入組在全因死亡、心血管死亡和心力衰竭的發(fā)生率上并無顯著差異。

      從2002年第一臺TAVI手術走進臨床,到近期全球激增的手術數(shù)量,TAVI操作方法、器材等均在不斷發(fā)展中,TAVI術后PPM植入也無統(tǒng)一共識,這些都影響了其預后研究的真實性和有效性,故需大樣本的長期臨床隨機試驗來進一步明確。

      5 總結

      綜上所述,盡管TAVI對比外科手術主動脈瓣植入有著更高的收益/風險比,但其顯著的術后并發(fā)癥仍應得到重視。這其中,TAVI術后傳導功能障礙導致的起搏器植入是最重要也是最復雜的術后并發(fā)癥,本篇綜述從TAVI術后傳導功能障礙的機制、預測因素以及PPI的指征、時機等多個方面對目前最新的研究進展進行了總結,希望能促進對于TAVI術后起搏器植入更加深入的了解,為將來深入研究打下基礎。

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      Permanent Pacemaker Implantation after Transcatheter Aortic Valve Implantation

      ZHAN Zhi,GUAN Lihua

      (DepartmentofCardiology,ZhongshanHospital,FudanUniversity,Shanghai200032,China)

      帶雙孔房間隔限流器造瘺對犬肺動脈高壓模型作用機制的研究 (14ZR1406700)

      詹智(1991—),住院醫(yī)師,在讀碩士,主要從事心血管病研究。Email:zhanzhi1991@163.com

      管麗華(1975—),副教授,副主任醫(yī)師,碩士,主要從事心血管病研究。Email: guan1301@hotmail.com

      2016-08-01

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