Ablation of atrial fibrillation-patient selection,periprocedural anticoagulation,techniques,and preventive measures after ablation

Patient Selection

Figure 1 Selection of patients with no or minimal structural heart disease for atrial fibrillation（AF） ablation.AAD indicates antiarrhythmic drug;LoE,Level of Evidence;LSPAF,long-standing persistent atrial fibrillation;PAF,paroxysmal atrial fibrillation;and PerAF,persistent atrial fibrillation.

Patient selection for ablation is a shared decision by the patient and physician.The odds of a successful ablation not only are related to the technique of the procedure but also are critically to patient characteristics.The ideal patient with the highest likelihood of procedural success is one with paroxysmal AF,no underlying cardiac disease,and a nondilated left atrium（Figure 1）.Paroxysmal AF is defined as AF ＜7 days in duration.Success rates with these patients approaches 80%.However,it has become clear in the last decade that even patients with persistent（＞7 days）and long-standing persistent（continuous AF ＞1 year）AF may also benefit from AF ablation.In addition,patients with congestive heart failure or decreased left ventricular ejection fraction may be candidates for AF ablation（Figure 2）.However,it is clear that the odds of a successful ablation are diminished with greater underlying heart disease.In particular,left atrial enlargement,mitral valve disease,and chronic heart failure are associated with poorer outcomes.It was once believed thatpatients need to failatleast1 antiarrhythmic agent before AF ablation.However,given the known toxicities of antiarrhythmic agents and the success of ablation,ablation is now acceptable as an initial rhythm control strategy,at least for paroxysmal AF.

Figure 2 Selection of patients with structural heart disease（SHD）for atrial fibrillation （AF）ablation.AAD indicates antiarrhythmic drug.

The latest AF ablation guidelines were updated in the United States in 2014 and in Europe in 2012（Table 1）.For patients with symptomatic paroxysmal AF,the latest American Heart Association/American College of Cardiology recommendations give a ClassⅠrecommendation （is useful）for catheter ablation in patients with paroxysmal AF who have failed or are intolerant of classⅠorⅢantiarrhythmic agents.These same guidelines give a IIa recommendation（is reasonable）for those symptomatic patients with paroxysmal AF who wish to pursue ablation as an initial rhythm strategy and patients with symptomatic persistent AF who have failed or are intolerant to a classⅠorⅢantiarrhythmic agent.

Table 1 P atient Selection for AF Ablation According to US and European Guidelines

Repeat ablations are necessary in many patients,particularly in those with underlying heart disease.In general,a younger age,greater severity of symptoms,and contribution of AF to heart failure/cardiomyopathy factor into1the decision for repeat ablations.In many of these individuals,repeat ablations should be performed.

Anticoagulation

The vitamin K antagonist warfarin has been the gold standard for anticoagulation in AF.Its ability to lower the risk of thromboembolism has been established by large randomized,controlled trials （RCTs） in the 1980s and early 1990s.However,warfarin therapy is complicated bytheneed fordietarycompliance,sensitivity to multiple medications,frequent blood draws for monitoring, and often unexplained INR（international normalized ratio） fluctuations.Thus,there has been a widespread desire to develop warfarin substitutes that are safer and easier to administer.

Dabigatran,a direct thrombin inhibitor,and the direct factor Xa inhibitors rivaroxaban,apixaban,and edoxaban are currently available. All of these newer/direct anticoagulants were tested against warfarin;they have not been directly compared with one another in a clinical trial.Although the clinical results of the trials are similar,there are differences in trial design,patient thromboembolic risk,and end points that prevent their direct comparison.

The CHA2DS2-VASc score has largely supplanted the CHADS score for the estimation of stroke risk in patients with AF.The CHA2DS2-VASc score includes 7 clinical characteristics （congestive heart failure,hypertension,age,diabetes mellitus,stroke/transient ischemic attack,vascular disease,female sex）to stratify stroke risk.In the US guidelines,individuals with a CHA2DS2-VASc score of≥2 are recommended to undergo anticoagulation.ESC guidelines recommend anticoagulation for those with a CHA2DS2-VASc score of≥1（IIa;should be considered for those with a score of 1）.The data on the risk of stroke in individuals with AF with a CHA2DS2-VASc score of 1 are conflicting and thus underlie the different recommendations in the United States and Europe.

Periprocedural prescription of anticoagulation is evolving.Initially,warfarin was held either with or without heparin bridging.Subsequent data emerged that showed that bleeding complications were actually lower with uninterrupted warfarin compared with a bridging strategy.In addition,uninterrupted strategies reduce both clinical and silent thromboembolic events.This pattern of withholding anticoagulation around the time of the ablation also applied to the direct anticoagulants,with some studies advocating bridging and others not.There is more concern about the treatment of bleeding complications with the direct anticoagulants because of the previous lack of reversal agents.Registry data have suggested that ablation can be performed without discontinuation of these agents,although often 1 or 2 doses are held before the procedure.In addition,the developmentofreversalagents forthese direct anticoagulants should provide more justification for uninterrupted anticoagulation at the time of the ablation.Continuation of anticoagulants should persist for at least 2 months after the procedure.Continuing anticoagulation for an extended time period depends on the CHA2DS2-VASc score.The 2012 ESC guidelines state that long-term anticoagulation is recommended in all patients with a CHA2DS2-VASc score of≥2,and the US guidelines agree that the decision for continued anticoagulation largely hinges on the CHA2DS2-VASc score.In the US guidelines,individuals with a low CHA2DS2-VASc score and successful ablation can likely stop anticoagulation after 2 to 3 months.Current guidelines do not recommend AF ablation for the sole purpose of discontinuation of anticoagulation.

Techniques

Techniques for AF ablation are maturing,and differences are not completely resolved.Techniques for the ablation of AF vary by energy source and location of atrial lesions（ie,lesion sets）.

Energy sources available for AF ablation include radiofrequency,cryoablation,and laser.Radiofrequency and cryoablation are currently most commonly used.Radiofrequency creates a lesion with heat（typically up to 60℃）and can be delivered with or without saline irrigation at the tip of the catheter.Irrigated-tip catheters reduce the risk of char formation and improve lesion depth and size;in general,they are the most commonly used catheters for radiofrequency ablation.New catheters with the ability to quantify the force of contact have recently been developed and appear to give more consistent lesions than prior catheters.Cryoablation is administered via a left atrial balloon that occludes each PV individually and freezes to-50℃.Laser ablation is performed with special catheters designed to create a circumferential lesion set around each PV.

The location of ablation lesions is where the major controversies in AF ablation lie.It is reasonably acknowledged that for individuals with paroxysmal AF and no underlying heart failure,electric isolation of the PVs at the antral level is associated with a high degree of elimination of AF.This isolation can be accomplished with radiofrequency,cryoablation,or laser energy.Randomized,clinical trials in this patient population generally compare an ablative technique with antiarrhythmic drug therapy.

Whether one ablative technique to isolate the PVs is superior to the other is not clear.Limited registry data have compared radiofrequency with cryoablation.In the German Ablation Registry,the recurrence rate at 1 year after a single procedure was≈45%in both groups.There have now been 2 RCTs comparing radiofrequency and cryoablation.In FREEZE AF,the reported success rates in the radiofrequency and cryoablation groups were comparable at 1-year follow up（63.1%versus 64.1%after a single procedure and 70.7%versus 73.6%after multiple procedures in the radiofrequency and cryoablation group,respectively）.In the recently published FIRE AND ICE （Cryoablation or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation）trial comparing radiofrequency and cryoablation in 762 patients with paroxysmal AF,the 1-year recurrences were 35.9% and 34.6% ,respectively.

In patients with nonparoxysmal AF,there is currently no one clearly preferred approach.In these individuals,isolation of the PVs alone may not be adequate to prevent recurrences.These additional lesion sets can be anatomically based or electrically guided.Anatomic guidance creates ablation lines in particular locations.The most common location is the roof between the right and left superior PVs （roof line）.Additional lines can be placed between the left and right inferior veins,left inferior PV,and mitral annulus（mitral line）.A cavotricuspid right-sided isthmus line may also be placed.However,reports from RCTs documenting outcomesofadditionallinearlesionshave been contradictory.Some RCTs have demonstrated benefits of adjunctive linear lesions in increasing arrhythmia-free survival rates in patients with nonparoxysmal AF undergoing PV isolation.In contrast,other RCTs have reported no additional advantages of a linear ablation approach over PV isolation alone in patients with AF,and the lines required significantly more ablation time,higher radiation doses,and longer procedure durations.

Electric lesion sets can be guided electrically by complex fractionated electric potentials or focal/reentrant sources（also described as rotors or drivers）.Complex fractionated electric potentials can be identified by individual operators or by special software analysis programs available in some commercial mapping systems.Focal/reentrant sources are currently mapped by an endocardial basket and specialized software FIRM（Focal Impulse and Rotor Mapping）or by surface mapping（Figure 6）.FIRM-guided ablation of persistent AF has shown higher 3-year freedom from AF compared with conventional ablation（single-procedure freedom from AF at 890 days,75%versus 30%）.

Relatively common periprocedural complications include groin hematomas,pericardial chest pain,and atrial irritability with atrial premature contractions and AF.Less common but more severe complications include cardiac perforation and tamponade（≈1%）,stroke or transient ischemic attack（≈1%）,vascular aneurysms or fistulas（≈1%）,PV stenosis（common previously but rare currently）,and phrenic nerve paralysis, particularly with cryoablation. Rare complications include mitral valve injury,myocardial infarction,air embolism,radiation injury,atrial esophageal fistula,gastric motility disorders,and death.

詞 匯

odds n.機(jī)會(huì)、機(jī)運(yùn)

candidates n.候選人、應(yīng)試者、考生

pursue v.追趕、追求、追隨、繼續(xù)

compliance n.順從、遵從、依從

fluctuation n.波動(dòng)，起伏

substitute n.&v.&adj.替代物，替代者；替代，取代，接替；替代的，臨時(shí)的

prescription n.&adj.規(guī)定，處方，書面醫(yī)囑；憑處方供應(yīng)的

cryoablation n.冷凍消融

char n.&v.炭，燒焦物；燒成炭，打雜，做

antral adj.竇的，前庭的

rotor n.轉(zhuǎn)子，旋筒，旋翼

motility n.能動(dòng)

注 釋

1.factor into指“成為（影響）…的”因素，factor可作為動(dòng)詞使用，但以這種主動(dòng)形式出現(xiàn)的很少見，通常以“be factored into”形式出現(xiàn)，如The comsumer's viewpoint should be factored into decision making.消費(fèi)者的觀點(diǎn)應(yīng)作為決策因素計(jì)入。

參考譯文

第87課 心房顫動(dòng)消融-患者選擇、圍手術(shù)期抗凝、技術(shù)及術(shù)后預(yù)防措施

患者選擇

患者消融的選擇由患者與醫(yī)師共同決策。成功消融的概率不但與手術(shù)技術(shù)有關(guān)，也與患者的特征明顯相關(guān)。手術(shù)成功率最高的理想患者是陣發(fā)性心房顫動(dòng)，無基礎(chǔ)心臟疾病和左心房擴(kuò)大（見圖1）。陣發(fā)性心房顫動(dòng)的定義是病程＜7d。這類患者的成功率達(dá)80%。不過，最近10年已明確即使持續(xù)性心房顫動(dòng)（＞7 d）和慢性心房顫動(dòng)也可從心房顫動(dòng)的消融中獲益。另外，充血性心力衰竭或射血分?jǐn)?shù)下降的患者也可選心房顫動(dòng)消融（見圖2）。但是，基礎(chǔ)心臟疾病較明顯者消融成功概率降低。特別是左心房擴(kuò)大、二尖瓣病變和慢性心力衰竭患者手術(shù)結(jié)果較差。先前認(rèn)為心房顫動(dòng)消融前至少有一種抗心律失常藥物無效。不過，鑒于抗心律失常藥物的已知毒性和消融的成功，消融術(shù)已成為初始節(jié)律控制的方案，至少適合陣發(fā)性心房顫動(dòng)。

最近的心房顫動(dòng)消融指南更新是2014美國和2012歐洲指南（見表1）。對(duì)于有癥狀的陣發(fā)性心房顫動(dòng)患者，最新的AHA/ACC建議Ⅰ類或Ⅲ類抗心律失常藥物治療無效或不能耐受的陣發(fā)性心房顫動(dòng)患者為Ⅰ類（有用的）建議，對(duì)于追求消融術(shù)作為首選節(jié)律控制方案的有癥狀的陣發(fā)性心房顫動(dòng)患者、Ⅰ類或Ⅲ類抗心律失常藥物無效或不能耐受的有癥狀的持續(xù)性心房顫動(dòng)患者為Ⅱa類（有理由的）建議。

許多患者，特別是那些有基礎(chǔ)心臟病者需要再次消融手術(shù)。總之，年輕的、癥狀較嚴(yán)重的、心房顫動(dòng)導(dǎo)致心力衰竭或心肌病的，成為再次消融手術(shù)決策的因素。這些個(gè)體中的多數(shù)，應(yīng)實(shí)施再次消融手術(shù)。

抗凝

維生素K拮抗劑華法林一直是心房顫動(dòng)抗凝的金標(biāo)準(zhǔn)。80年代和90年代早期的大規(guī)模隨機(jī)、對(duì)照試驗(yàn)已確立它能降低血栓栓塞的風(fēng)險(xiǎn)。然而，華法林治療的復(fù)雜性在于需要飲食順從、對(duì)多種藥物敏感、需頻繁抽血監(jiān)測(cè)以及經(jīng)常出現(xiàn)不能解釋的國際標(biāo)準(zhǔn)化比值（INR）波動(dòng)。這樣，普遍希望發(fā)展一種對(duì)使用者既安全又方便的華法林替代物。

直接凝血酶抑制劑達(dá)比加全，直接Xa抑制劑利伐沙坦、阿哌沙坦和依度沙班現(xiàn)已面市。所有這些新型或直接的抗凝劑都與華法林做對(duì)比測(cè)試。它們相互之間未做直接比較的臨床試驗(yàn)。盡管試驗(yàn)的臨床結(jié)果類似，但試驗(yàn)的設(shè)計(jì)、患者血栓栓塞的風(fēng)險(xiǎn)和預(yù)防的終點(diǎn)存在差異，這妨礙了它們之間的直接比較。

CHA2DS2-VASc評(píng)分較大程度上取代了CHADS評(píng)估心房顫動(dòng)患者中風(fēng)風(fēng)險(xiǎn)。CHA2DS2-VASc評(píng)分納入7個(gè)臨床特征（充血性心力衰竭、高血壓、年齡、糖尿病、腦卒中/短暫腦缺血發(fā)作、動(dòng)脈疾病和女性）對(duì)腦卒中風(fēng)險(xiǎn)進(jìn)行分層。美國指南建議對(duì)CHA2DS2-VASc評(píng)分≥2分的個(gè)體進(jìn)行抗凝治療。ESC指南建議對(duì)CHA2DS2-VASc評(píng)分≥1分的人群進(jìn)行抗凝治療（而CHA2DS2-VASc=1分的定為Ⅱa類推薦）。有關(guān)CHA2DS2-VASc=1分患者的中風(fēng)風(fēng)險(xiǎn)資料存在沖突，從而導(dǎo)致美國與歐洲指南的不同。

圍手術(shù)期抗凝方案不斷演變中。最初是停用華法林，橋接或不橋接肝素。隨后的資料顯示，與橋接方案比較，不停用華法林的出血并發(fā)癥竟然較低。此外，不停用方案減少臨床的和隱匿的血栓栓塞事件。這種圍消融手術(shù)期停用抗凝劑的方式也應(yīng)用到直接抗凝劑，有些研究?jī)A向于橋接，而另一些不是。更多關(guān)注的是直接抗凝劑的出血并發(fā)癥，因?yàn)榇饲叭狈ο鄳?yīng)的逆轉(zhuǎn)制劑。注冊(cè)資料表明可以在不停用這些抗凝劑的情況下進(jìn)行消融手術(shù)，雖然在消融前常常停1～2次。另外，這些直接抗凝劑逆轉(zhuǎn)制劑的出現(xiàn)將為消融手術(shù)時(shí)不停用抗凝劑提供更為充分的依據(jù)。

消融手術(shù)后連續(xù)抗凝治療應(yīng)持續(xù)至少2個(gè)月。持續(xù)抗凝延長(zhǎng)時(shí)間決定于CHA2DS2-VASc評(píng)分。2012年ESC指南建議所有CHA2DS2-VASc評(píng)分 2分的患者應(yīng)長(zhǎng)期抗凝治療，美國指南同意持續(xù)抗凝的決策基本上依據(jù)CHA2DS2-VASc評(píng)分而定。對(duì)CHA2DS2-VASc評(píng)分低且成功消融的個(gè)體，美國指南建議2～3個(gè)月后停用抗凝劑。當(dāng)前指南推薦心房顫動(dòng)消融手術(shù)的理由并非只是為了停用抗凝劑。

消融技術(shù)

心房顫動(dòng)的消融技術(shù)處在成熟的過程中，差異沒有完全解決。心房顫動(dòng)的消融技術(shù)因能源和心房病變（病灶）部位而異。

用于心房顫動(dòng)消融的能源包括射頻、冷凍和激光。目前極大多數(shù)使用射頻和激光。射頻作用源于熱損傷（通常達(dá)60℃），可使用有或無頭端鹽水灌注的導(dǎo)管實(shí)施。灌注導(dǎo)管減少積碳形成的風(fēng)險(xiǎn)、提高損傷深度和范圍，總之，這是最為常用的射頻消融導(dǎo)管。近期生產(chǎn)出的新導(dǎo)管能夠確定接觸的力度，似乎較此前的導(dǎo)管產(chǎn)生更為一致的損傷。冷凍消融通過左心房球囊而實(shí)施，球囊分別堵塞每一個(gè)肺靜脈冰凍至-50℃。激光消融通過特殊的導(dǎo)管實(shí)施，環(huán)繞每個(gè)肺靜脈產(chǎn)生環(huán)形損傷。

消融損傷的部位是心房顫動(dòng)消融的主要爭(zhēng)論所在。普遍公認(rèn)的是對(duì)于陣發(fā)性心房顫動(dòng)且無心力衰竭者，于前庭水平電隔離肺靜脈能極大地消除心房顫動(dòng)。這種隔離可通過射頻、冷凍或激光完成。這一人群的隨機(jī)臨床試驗(yàn)通常將消融技術(shù)與抗心律失常藥物治療作比較。

在隔離肺靜脈上，尚不明確某種消融技術(shù)是否優(yōu)于其他技術(shù)。有限的注冊(cè)資料對(duì)射頻和冷凍消融做了比較。在德國的消融注冊(cè)中，單次手術(shù)1年后復(fù)發(fā)率兩組均接近45%。目前有兩項(xiàng)隨機(jī)對(duì)照臨床試驗(yàn)對(duì)射頻消融與冷凍消融作了比較。FREEZE AF研究報(bào)告，射頻與冷凍消融后隨訪1年的成功率接近（單次消融后為63.1%比64.1%，多次消融后為70.7%比73.6%）。最近出版的FIRE AND ICE（陣發(fā)性心房顫動(dòng)的冷凍或射頻消融治療）試驗(yàn)對(duì)762例陣發(fā)性心房顫動(dòng)患者的射頻和冷凍消融進(jìn)行了比較，1年的復(fù)發(fā)率分別為35.9%和34.6%。

對(duì)于非陣發(fā)性心房顫動(dòng)患者，目前缺乏明確優(yōu)選的方法。在這些人群，單純肺靜脈隔離不足以防范復(fù)發(fā)，可根據(jù)解剖或電學(xué)引導(dǎo)消融這些外加部位。特殊部位由解剖引導(dǎo)產(chǎn)生消融線。最常見的部位是位于左右上肺靜脈之間的頂部（頂線），附加線可位于左右下靜脈，左下肺靜脈，和二尖瓣環(huán)（二尖瓣線）之間。還有腔靜脈三尖瓣右側(cè)峽部線。然而，附加線消融預(yù)后的隨機(jī)臨床對(duì)照研究報(bào)告存在矛盾。有些隨機(jī)對(duì)照研究證實(shí)附加線消融有益于非陣發(fā)性心房顫動(dòng)肺靜脈隔離患者的無心律失常生存率提高。相反，其他隨機(jī)對(duì)照研究報(bào)告顯示對(duì)于心房顫動(dòng)患者，在單純肺靜脈隔離的基礎(chǔ)上加線性消融方法并無額外獲益，卻明顯增加消融時(shí)間，射線量較大，手術(shù)時(shí)間較長(zhǎng)。

可由復(fù)雜的碎裂電位或局部/折返源（又稱轉(zhuǎn)子或驅(qū)動(dòng)器）從電學(xué)方面來探查電機(jī)能障礙部位。復(fù)雜碎裂電位由具體術(shù)者或某些商業(yè)標(biāo)測(cè)系統(tǒng)中的特別軟件分析程序識(shí)別。局部/折返源當(dāng)前通過心內(nèi)膜藍(lán)（藍(lán)狀電極-譯者注）和特殊軟件FIRM（局部沖動(dòng)和轉(zhuǎn)子標(biāo)測(cè)）或體表標(biāo)測(cè)來標(biāo)測(cè)。FIRM引導(dǎo)的持續(xù)性心房顫動(dòng)消融表明，與常規(guī)消融比較，3年無心房顫動(dòng)比例較高（單次手術(shù)后890天的無心房顫動(dòng)率從30%提高到75%）。

較常見的圍手術(shù)期并發(fā)癥包括股部血腫、心包胸痛和伴隨心房期前激動(dòng)與心房顫動(dòng)的心房易激。少見但更嚴(yán)重的并發(fā)癥包括心臟穿孔和填塞、中風(fēng)或短暫腦缺血發(fā)作、動(dòng)脈瘤或瘺、肺靜脈狹窄和膈神經(jīng)麻痹，特別是冷凍消融。少見的并發(fā)癥包括二尖瓣損傷、心肌梗死、氣栓、放射損傷、心房食道瘺、胃動(dòng)力障礙和死亡。

圖1無或輕微結(jié)構(gòu)性心臟疾病患者心房顫動(dòng)消融的選擇。AAD：抗心律失常藥物了；LoE：依據(jù)水平；LSPAF：慢性持續(xù)性心房顫動(dòng)；PAF：陣發(fā)性心房顫動(dòng)；PerAF：持續(xù)性心房顫動(dòng)。

圖2結(jié)構(gòu)性心臟病患者的心房顫動(dòng)消融選擇。AAD：抗心律失常藥物。

表1基于美國和歐洲指南的心房顫動(dòng)消融患者選擇