坎地沙坦對陣發性房顫射頻消融術后復發及房顫發作持續時間的影響

張芳 夏振偉 馮磊 王小斌

·藥物與臨床·

坎地沙坦對陣發性房顫射頻消融術后復發及房顫發作持續時間的影響

張芳 夏振偉 馮磊 王小斌

目的 探討坎地沙坦對陣發性心房顫動(房顫)射頻消融術后復發及房顫發作持續時間的影響。方法 64例陣發性房顫患者,均給予射頻消融術治療,術后隨機分為治療組和對照組,每組32例。治療組口服坎地沙坦,對照組未給予藥物。觀察比較兩組的復發次數及房顫持續時間。結果 隨訪8～12個月,治療組平均每例房顫復發次數(8.5±1.2)次少于對照組的(10.1±1.5)次,差異具有統計學意義(P＜0.01)。治療組平均房顫發作持續時間(10.5±2.3)min/次短于對照組的(41.3±3.6)min/次,差異具有統計學意義(P＜0.01)。結論 坎地沙坦可減少陣發性房顫射頻消融術后的復發情況,且可縮短房顫發作持續時間。

陣發性心房顫動；射頻消融術；坎地沙坦；復發；發作持續時間

房顫是臨床最常見的一種心律失常。目前,抗心律失常藥物治療和導管消融治療是房顫患者轉復和維持竇律的主要方法,但是,上述兩種方法的成功率不盡如人意。近年來,有研究顯示,非抗心律失常藥物如血管緊張素轉化酶抑制劑、血管緊張素Ⅱ受體拮抗劑及他汀類藥物可減少部分患者房顫的初發及復發［1-3］。本文通過探討坎地沙坦對陣發性房顫射頻消融術后復發及房顫發作持續時間的影響,現報告如下。

1 資料與方法

1.1 一般資料 選取2014年3月～2015年6月本院收治的陣發性房顫患者64例,年齡45～70歲,平均年齡(56.2±6.3)歲,所有患者均給予射頻消融術治療術后隨機分為對照組與治療組,每組32例。排除器質性心臟病和甲狀腺功能亢進。

1.2 方法 所有患者入組前常規停用抗心律失常藥物2周,行超聲心動圖檢查排除瓣膜性心臟病,行肺靜脈增強CT明

確有無左房血栓,對發作頻繁或發作持續時間較長者需經食管超聲除外心房血栓；其他術前準備同普通射頻消融術。所有患者在三維標測系統指導下,在肺靜脈外口0.5～1.0 cm的左心房完成環狀消融。消融終點是消融線兩側雙向傳導阻滯。對復發的患者進行再次消融時,均再次行電生理檢查,術中所用標測及消融設備相同,并由同一術者完成。所有患者均未發生心包填塞。術后華法令抗凝3個月,維持國際標準化比值(INR)1.8～2.5之間。術后對照組未給予藥物,治療組口服坎地沙坦(武田藥品工業株式會社)4 mg,1次/d,6個月后,治療組及對照組均有1例患者失訪,余患者均完成研究。患者房顫復發時用電復律或鹽酸普羅帕酮復律,未長期口服抗心律失常藥物。

1.3 觀察指標 記錄兩組患者隨訪期間房顫復發次數及房顫發作持續時間,并進行比較。

1.4 統計學方法 采用SPSS17.0統計學軟件處理數據。計量資料以均數±標準差(±s)表示,采用t檢驗。P＜0.05表示差異具有統計學意義。

2 結果

隨訪8～12個月,治療組平均每例房顫復發次數(8.5±1.2)次,對照組平均每例房顫復發次數(10.1±1.5)次,治療組平均每例房顫復發次數明顯少于對照組,差異具有統計學意義(P＜0.01)。治療組平均房顫發作持續時間(10.5±2.3)min/次,對照組平均房顫發作持續時間(41.3±3.6)min/次,治療組平均房顫發作持續時間明顯短于對照組,差異具有統計學意義(P＜0.01)。

3 討論

房顫增加患者心力衰竭、腦卒中、死亡風險［4］。房顫的發病率隨年齡增長而增加［5］。房顫的機制至今未明。目前,多數研究提示心房電重構、心房結構重構和炎癥可能參與其中。心房結構重構的早期是心房電重構,晚期是心房纖維化、淀粉沉積、細胞凋亡等組織學改變。近期有研究提示腎素-血管緊張素系統在心房結構重整過程中,起了重要作用［6］。血管緊張素轉化酶促進血管緊張素Ⅰ轉化成血管緊張素Ⅱ,激活血管緊張素受體-1,血管緊張素受體-1通過G蛋白介導引發磷酸化瀑布鏈式反應,并作用于細胞外信號激酶和活化轉錄因子等,刺激成纖維細胞的增值、肥大和凋亡。另有多項研究提示血管緊張素Ⅱ可以導致藥物性心律失常［7］。在基礎研究和臨床試驗中也發現心肌纖維化組織中血管緊張素轉化酶表達增加、血管緊張素Ⅱ相關的信號通路激活［8-12］。

如果阻斷血管緊張素Ⅱ,可延緩心房纖維化,減少房顫復發。本研究發現：坎地沙坦治療組房顫復發次數少于對照組,房顫發作持續時間短于對照組,差異均具有統計學意義(P＜0.01),進而證實血管緊張素Ⅱ受體拮抗劑可減少房顫射頻消融術后的復發情況,并縮短房顫發作持續的時間。結果也提示：現階段,抗心律失常藥物和導管消融在房顫轉復和維持竇律的成功率有限,加用非抗心律失常藥物(如血管緊張素Ⅱ受體拮抗劑)可進一步提高房顫心律治療的效果。因本研究嚴格控制入組條件,所以入選病例數少,且隨訪時間短、隨訪方法有限、缺失部分無癥狀房顫的結果,可能對本研究結果產生影響。因此,后續研究將持續進行。

［1］Savelieva I,Kakouros N,Kourliouros A,et al.Upstream therapies for management of atrial fibrillation: review of clinicalevidence and implications for European Society of Cardiology guidelines.Part I: primary prevention.Europace,2011,13(3):308-328.

［2］Savelieva I,Kakouros N,Kourliouros A,et al.Upstream therapies for management of atrial fibrillation: review of clinicalevidence and implications for European Society of Cardiology guidelines.Part II: secondary prevention.Europace,2011,13(5):610-625.

［3］Khatib R,Joseph P,Briel M,et al.Blockade of the reninangiotensin-aldosterone system (RAAS) for primary preventionof non-valvular atrial fibrillation: a systematic review and meta analysis ofrandomized controlled trials.Int J Cardiol,2013,165(1):17-24.

［4］January CT,Wann LS,Alpert JS,et al.2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Forceon Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol,2014,64(21):e1-e76.

［5］Disertori M,Lombardi F,Barlera S,et al.Clinical predictors of atrial fibrillation recurrence in the Gruppo Italiano per loStudio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSIAF)trial.Am Heart J,2010,159(5):857-863.

［6］Yagi S,Akaike M,Aihara K,et al.Endothelial nitric oxide synthaseindependent protective action of statin againstangiotensin II-induced atrial remodeling via reduced oxidant injury.Hypertension,2010,55(4):918-923.

［7］Schmieder RE,Hilgers KF,Schlaich MP,et al.Renin-angiotensin system and cardiovascular risk.Lancet,2007,369(9568):1208-1219.

［8］Novo G,Guttilla D,Fazio G,et al.The role of the renin-angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS.Br J Clin Pharmacol,2008,66(3):345-351.

［9］Dixen U,Ravn L,Soeby-Rasmussen C,et al.Raised plasma aldosterone and natriuretic peptides in atrial fibrillation.Cardiology,2007,108(1):35-39.

［10］Ehrlich JR,Hohnloser SH,Nattel S.Role of angiotensin system and effects of its inhibition in atrial fibrillation:clinical and experimental evidence.Eur Heart J,2006,27(5):512-518.

［11］Goette A,Staack T,Rcken C,et al.Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.J Am Coll Cardiol,2000,35(6):1669-1677.

［12］Xie X,Liu Y,Gao S,et al.Possible involvement of fibrocytes in atrial fibrosis in patients with chronicatrial fibrillation.Circ J,2014,78(2):338-344.

Influence of candesartan on recurrence and duration of atrial fibrillation attack after radiofrequency ablation for paroxysmal atrial fibrillation

ZHANG Fang,XIA Zhen-wei,FENG Lei,et al.Department of Cardiology,Liaoning Province Dalian City Central Hospital,Dalian 116033,China

ObjectiveTo explore influence of candesartan on recurrence and duration of atrial fibrillation attack after radiofrequency ablation for paroxysmal atrial fibrillation.MethodsA total of 64 paroxysmal atrial fibrillation patients all treated with radiofrequency ablation were randomly divided into treatment group and control group,with 32 cases in each group.The treatment group received oral candesartan,and the control group received no medicine.Observation and comparison were made on recurrent frequency and duration of the atrial fibrillation attack in two groups.ResultsAfter follow-up review for 8～12 months,the treatment group had less average recurrence of atrial fibrillation as (8.5±1.2) times than (10.1±1.5) times in the control group,and their differences had statistical significance (P＜0.01).The treatment group had shorter average duration of atrial fibrillation attack as (10.5±2.3) min/time than (41.3±3.6) min/time in the control group,and their difference had statistical significance (P＜0.01).ConclusionCandesartan can reduce the recurrence after radiofrequency ablation for paroxysmal atrial fibrillation,and also can shorten the duration of atrial fibrillation attack.

Paroxysmal atrial fibrillation; Radiofrequency ablation; Candesartan; Recurrence; Duration of attack

10.14164/j.cnki.cn11-5581/r.2017.03.039

2016-12-28］

116033 遼寧省大連市中心醫院心內科