張芳 夏振偉 馮磊 王小斌

·藥物與臨床·

坎地沙坦對(duì)陣發(fā)性房顫射頻消融術(shù)后復(fù)發(fā)及房顫發(fā)作持續(xù)時(shí)間的影響

張芳 夏振偉 馮磊 王小斌

目的 探討坎地沙坦對(duì)陣發(fā)性心房顫動(dòng)(房顫)射頻消融術(shù)后復(fù)發(fā)及房顫發(fā)作持續(xù)時(shí)間的影響。方法 64例陣發(fā)性房顫患者,均給予射頻消融術(shù)治療,術(shù)后隨機(jī)分為治療組和對(duì)照組,每組32例。治療組口服坎地沙坦,對(duì)照組未給予藥物。觀察比較兩組的復(fù)發(fā)次數(shù)及房顫持續(xù)時(shí)間。結(jié)果 隨訪8～12個(gè)月,治療組平均每例房顫復(fù)發(fā)次數(shù)(8.5±1.2)次少于對(duì)照組的(10.1±1.5)次,差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01)。治療組平均房顫發(fā)作持續(xù)時(shí)間(10.5±2.3)min/次短于對(duì)照組的(41.3±3.6)min/次,差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01)。結(jié)論 坎地沙坦可減少陣發(fā)性房顫射頻消融術(shù)后的復(fù)發(fā)情況,且可縮短房顫發(fā)作持續(xù)時(shí)間。

陣發(fā)性心房顫動(dòng)；射頻消融術(shù)；坎地沙坦；復(fù)發(fā)；發(fā)作持續(xù)時(shí)間

房顫是臨床最常見(jiàn)的一種心律失常。目前,抗心律失常藥物治療和導(dǎo)管消融治療是房顫患者轉(zhuǎn)復(fù)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(lái),有研究顯示,非抗心律失常藥物如血管緊張素轉(zhuǎn)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(fā)及復(fù)發(fā)［1-3］。本文通過(guò)探討坎地沙坦對(duì)陣發(fā)性房顫射頻消融術(shù)后復(fù)發(fā)及房顫發(fā)作持續(xù)時(shí)間的影響,現(xiàn)報(bào)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(fā)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(shù)治療術(shù)后隨機(jī)分為對(duì)照組與治療組,每組32例。排除器質(zhì)性心臟病和甲狀腺功能亢進(jìn)。

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

確有無(wú)左房血栓,對(duì)發(fā)作頻繁或發(fā)作持續(xù)時(shí)間較長(zhǎng)者需經(jīng)食管超聲除外心房血栓；其他術(shù)前準(zhǔn)備同普通射頻消融術(shù)。所有患者在三維標(biāo)測(cè)系統(tǒng)指導(dǎo)下,在肺靜脈外口0.5～1.0 cm的左心房完成環(huán)狀消融。消融終點(diǎn)是消融線兩側(cè)雙向傳導(dǎo)阻滯。對(duì)復(fù)發(fā)的患者進(jìn)行再次消融時(shí),均再次行電生理檢查,術(shù)中所用標(biāo)測(cè)及消融設(shè)備相同,并由同一術(shù)者完成。所有患者均未發(fā)生心包填塞。術(shù)后華法令抗凝3個(gè)月,維持國(guó)際標(biāo)準(zhǔn)化比值(INR)1.8～2.5之間。術(shù)后對(duì)照組未給予藥物,治療組口服坎地沙坦(武田藥品工業(yè)株式會(huì)社)4 mg,1次/d,6個(gè)月后,治療組及對(duì)照組均有1例患者失訪,余患者均完成研究?；颊叻款潖?fù)發(fā)時(shí)用電復(fù)律或鹽酸普羅帕酮復(fù)律,未長(zhǎng)期口服抗心律失常藥物。

1.3 觀察指標(biāo) 記錄兩組患者隨訪期間房顫復(fù)發(fā)次數(shù)及房顫發(fā)作持續(xù)時(shí)間,并進(jìn)行比較。

1.4 統(tǒng)計(jì)學(xué)方法 采用SPSS17.0統(tǒng)計(jì)學(xué)軟件處理數(shù)據(jù)。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(±s)表示,采用t檢驗(yàn)。P＜0.05表示差異具有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

隨訪8～12個(gè)月,治療組平均每例房顫復(fù)發(fā)次數(shù)(8.5±1.2)次,對(duì)照組平均每例房顫復(fù)發(fā)次數(shù)(10.1±1.5)次,治療組平均每例房顫復(fù)發(fā)次數(shù)明顯少于對(duì)照組,差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01)。治療組平均房顫發(fā)作持續(xù)時(shí)間(10.5±2.3)min/次,對(duì)照組平均房顫發(fā)作持續(xù)時(shí)間(41.3±3.6)min/次,治療組平均房顫發(fā)作持續(xù)時(shí)間明顯短于對(duì)照組,差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01)。

3 討論

房顫增加患者心力衰竭、腦卒中、死亡風(fēng)險(xiǎn)［4］。房顫的發(fā)病率隨年齡增長(zhǎng)而增加［5］。房顫的機(jī)制至今未明。目前,多數(shù)研究提示心房電重構(gòu)、心房結(jié)構(gòu)重構(gòu)和炎癥可能參與其中。心房結(jié)構(gòu)重構(gòu)的早期是心房電重構(gòu),晚期是心房纖維化、淀粉沉積、細(xì)胞凋亡等組織學(xué)改變。近期有研究提示腎素-血管緊張素系統(tǒng)在心房結(jié)構(gòu)重整過(guò)程中,起了重要作用［6］。血管緊張素轉(zhuǎn)化酶促進(jìn)血管緊張素Ⅰ轉(zhuǎn)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(guò)G蛋白介導(dǎo)引發(fā)磷酸化瀑布鏈?zhǔn)椒磻?yīng),并作用于細(xì)胞外信號(hào)激酶和活化轉(zhuǎn)錄因子等,刺激成纖維細(xì)胞的增值、肥大和凋亡。另有多項(xiàng)研究提示血管緊張素Ⅱ可以導(dǎo)致藥物性心律失常［7］。在基礎(chǔ)研究和臨床試驗(yàn)中也發(fā)現(xiàn)心肌纖維化組織中血管緊張素轉(zhuǎn)化酶表達(dá)增加、血管緊張素Ⅱ相關(guān)的信號(hào)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(fù)發(fā)。本研究發(fā)現(xiàn)：坎地沙坦治療組房顫復(fù)發(fā)次數(shù)少于對(duì)照組,房顫發(fā)作持續(xù)時(shí)間短于對(duì)照組,差異均具有統(tǒng)計(jì)學(xué)意義(P＜0.01),進(jìn)而證實(shí)血管緊張素Ⅱ受體拮抗劑可減少房顫射頻消融術(shù)后的復(fù)發(fā)情況,并縮短房顫發(fā)作持續(xù)的時(shí)間。結(jié)果也提示：現(xiàn)階段,抗心律失常藥物和導(dǎo)管消融在房顫轉(zhuǎn)復(fù)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(jìn)一步提高房顫心律治療的效果。因本研究嚴(yán)格控制入組條件,所以入選病例數(shù)少,且隨訪時(shí)間短、隨訪方法有限、缺失部分無(wú)癥狀房顫的結(jié)果,可能對(duì)本研究結(jié)果產(chǎn)生影響。因此,后續(xù)研究將持續(xù)進(jìn)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(yī)院心內(nèi)科