心脏手术中可安全实施房颤消融术

慕尼黑——8月28日，在欧洲心脏病学会(ESC)2012年会上，捷克布拉格查理大学教授、心脏中心主任Petr Widimsky博士报告了一项纳入患有房颤并且因其他原因需接受心脏手术的患者的多中心随机试验，结果显示针对房颤的左房消融治疗可以安全用于开放性心脏手术中。而且，与仅接受开放性心脏手术的对照组患者相比，消融治疗组恢复窦性心律的患者比例显著增加，提示消融治疗有效。


Petr Widimsky博士

PRAGUE-12试验于2007~2011年在捷克斯洛伐克的3个医疗中心招募了224例需要接受冠状动脉旁路移植术、瓣膜修补或置换术或者同时需要施行这2种手术的房颤患者。经过随机分组，其中117例患者在心脏手术中接受左房消融治疗，另外107例则只接受其心脏手术(对照组)。手术医生可以自由选择消融治疗的能量来源，但97%使用的是冷冻消融术。消融治疗组所有患者的消融灶设置都是一样的。

患者的平均年龄在70岁左右，男性约占58%。大约半数患者为长程持续性房颤，1/4为持续性房颤，另外1/4为阵发性房颤。所有患者都经正中胸骨切开后在体外循环心肺转流和心脏停跳状态下接受开放性心脏手术。术中增加消融治疗使总手术时间平均延长了20分钟，使心肺转流和主动脉夹闭时间平均延长了28分钟。

主要安全性终点为术后30天内死亡、卒中、心肌缺血或需要透析的肾脏衰竭的复合发生率。消融治疗组和对照组的这一复合发生率分别为10%和15%，差异无统计学意义，并且具体某一种事件的发生率也没有组间差异。术后1年，消融治疗组和对照组的复合不良事件发生率分别为41%和40%。

该试验的主要疗效终点为根据24 h动态心电图监测来判断的窦性心律获得率，消融治疗组和对照组分别为60%和36%，差异有统计学意义。这一差异主要来自入组试验时合并有长程持续性房颤的患者亚组。在这一亚组中，术后1年恢复了窦性心律的患者比例在消融治疗组和对照组中分别为53%和14%，差异非常显著。相比之下，对于入组试验时合并有阵发性房颤或者持续性房颤的患者亚组，术后1年窦性心律的获得率并无显著的组间差异。

听取了上述发言的部分专家对于试验随访期抗心律失常效应模式和其他房颤相关结局提出了一些质疑。德国莱比锡大学心脏中心医学教授、电生理室主任Gerhard Hindricks博士说：“该试验的心律结局多少有些令人吃惊。只有长程持续性房颤患者从消融治疗中受益，这与之前的导管消融治疗和外科消融治疗的研究结果完全不符。”

Hindricks博士及其同事还在随刊述评中写道：“该试验的次要结局也让人意外，因为房颤应答后并没有改变抗心律失常药物的使用，两组1年后卒中、大出血和全因死亡的发生率也没有差异，尽管房颤持续的发生率存在组间差异。”Hindricks博士认为该试验在术后1年随访时仅采用24小时动态心电图监测来评估房颤是不够的。“这样的随访方案远不能得出令人信服的可靠结果。”(Eur. Heart J. 2012;33 [doi: 10.1093/eurheartj/ehs294])。

鉴于上述令人意外的结果，Hindricks博士建议“针对房颤的外科消融治疗应该慎用于准备接受心脏手术的无症状性患者”。

意大利米兰Policlinico San Donato医院临床心律失常与电生理中心主任Riccardo Cappato博士说：“这是评估房颤消融治疗用于心脏手术中的几项前瞻性随机试验中规模最大的一项。虽然永久性房颤患者维持窦性心律的几率会增加，但似乎还不足以抵消术中消融治疗导致的围手术期风险增加。”

Riccardo Cappato博士

这项PRAGUE-12试验的结果同步在线发表于《欧洲心脏杂志》上(Eur. Heart J. 2012;33 [doi: 10.1093/eurheartj/ehs290])。

Widimsky博士及其同事均声明无相关经济利益冲突。

随刊述评：进一步证实了术中消融治疗的安全性

当James L. Cox博士将Cox-Maze Ⅲ手术引入房颤患者的外科治疗时，由于这种技术需要较长时间的切割和缝合，并且也会延长心肺转流和主动脉夹闭的时间，因此带来了许多风险，包括神经系统并发症和肾脏衰竭。而这项研究采用的是改良Maze技术，以冷冻消融为主。由于改良后的技术无需切割和缝合，大大降低了手术难度，也减少了并发症风险。外科医生应该会对既安全又能增加窦性心律恢复几率的消融手术感兴趣。

这项研究的意义在于，证明了这种方法不仅安全而且提高了静息状态下窦性心律的维持率。奇怪的是这种治疗的主要效益体现在了长程持续性房颤患者中，而一般来讲这部分患者的治疗难度更大。不过，这可能与该试验的方法学问题有关，因其只评估了术后1年的心律结局，而没有继续开展连续心电监测。对于阵发性房颤患者而言，如果不连续监测1周以上就很难判定治疗是否成功。

Miguel Sousa Uva博士

这项研究所传递的主要信息是在心脏手术中实施消融治疗是安全的，不会明显延长手术时间或者增加手术的复杂程度。我认为这些结果将会增加在其他原因心脏手术中实施消融治疗的使用率。这应该说是一个很大的贡献。

MIGUEL SOUSA UVA博士是葡萄牙里斯本Cruz Vermelha医院的心脏外科医生，他在接受采访时做出了上述评价。他声明无相关经济利益冲突。

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By: MITCHEL L. ZOLER, Cardiology News Digital Network

MUNICH – Left atrial ablative treatment for atrial fibrillation was safe when administered during open heart surgery in a multicenter, randomized trial of 224 patients who all had atrial fibrillation and required heart surgery for another reason.

The treatment was also effective, resulting in a significantly higher rate of sinus rhythm among the patients treated with ablation compared with the control patients who underwent open-heart surgery alone, Dr. Petr Widimsky reported at the annual congress of the European Society of Cardiology on Aug. 28.
 
Some experts who heard the findings expressed some skepticism about the pattern of anti-arrhythmic effects and other atrial fibrillation–related outcomes during follow-up.

"The rhythm outcomes had some surprises. All the benefit was in patients with long-standing, persistent atrial fibrillation; that’s very surprising because it contrasts with previous findings from both catheter ablation and surgical ablation," said Dr. Gerhard Hindricks, a professor of medicine and director of the department of electrophysiology at the Heart Center of Leipzig (Germany) University.

"The secondary outcomes were also a surprise, because the atrial fibrillation response did not translate into a change in treatment" in the use of anti-arrhythmic drugs, and the two groups showed no differences in the 1-year rates of stroke, major bleeding, and all-cause mortality despite the reported different rates of continued AF. In an editorial that accompanied the published paper, Dr. Hindricks cited the inadequacy of assessing atrial arrhythmia at 1-year follow-up with 24-hour Holter ECG monitoring. "This follow-up regimen is by far not enough to generate reliable and solid results," Dr. Hindricks and his coauthor wrote (Eur. Heart J. 2012;33 [doi: 10.1093/eurheartj/ehs294]).

Despite these unexpected findings, "surgical ablation of atrial fibrillation should be cautiously indicated in asymptomatic patients scheduled for cardiac surgery," Dr. Hindricks said in comments he made at the meeting.

"This was the largest" of several randomized, prospective studies that have assessed ablation of atrial fibrillation during cardiac surgery, said Dr. Riccardo Cappato, director of the Center of Clinical Arrhythmia and Electrophysiology at the Policlinico San Donato in Milan. "The increased probability of maintaining sinus rhythm in patients with permanent atrial fibrillation does not seem to have been at the expense of higher perioperative risk exposure."
 
The PRAGUE-12 study enrolled 224 patients with AF who required cardiac surgery for coronary artery bypass, valve repair or replacement, or both at three centers in the Czech Republic and Slovakia during 2007-2011. The investigators randomized 117 patients to undergo atrial ablation during their surgery, and 107 who received no ablation with their surgery and served as controls. The surgeons could use whichever energy source for ablation they preferred, but 97% used cryoablation. The ablation-lesion set was the same for all patients in that treatment arm.

The patients averaged about 70 years old, and about 58% were men. Roughly half the patients had long-standing persistent AF, about a quarter had persistent AF, and the remaining quarter had paroxysmal AF.

All patients underwent open surgery using a median sternotomy with cardiopulmonary bypass and cardioplegic heart arrest. Adding ablation to the procedures increased the total surgical time by an average of 20 minutes, and increased the period of cardiopulmonary bypass and the cross-clamp time by an average of 28 minutes.

The primary safety end point was the combined rate of death, stroke, myocardial ischemia, or renal failure requiring dialysis at 30 days after surgery; this occurred in 10% of the patients who had ablation and 15% of the control patients, a nonsignificant difference, reported Dr. Widimsky, professor and head of the Cardiocenter of Charles University in Prague. Each component of the combined adverse event was similar between the two study arms. At 1 year after surgery, the combined adverse event rate was 41% in the patients treated with AF ablation and 40% in the controls.

The study’s primary efficacy end point was the prevalence of sinus rhythm in patients as measured by 24-hour Holter ECG monitoring, which occurred in 60% of the patients who underwent ablation and in 36% of the controls, a significant difference. This difference was driven by the outcome difference among the subgroup of patients who entered the study with long-standing persistent AF. In this subgroup, the proportion of patients in sinus rhythm when assessed after 1 year was 53% in the ablated group and 14% in the controls, a significant difference. In contrast, the prevalence of sinus rhythm at 1 year did not differ significantly between the two treatment arms in patients who entered the study with paroxysmal AF, or in those who entered with persistent AF.

Concurrent with the presentation of PRAGUE-12, the results also appeared in an article published online (Eur. Heart J. 2012;33 [doi: 10.1093/eurheartj/ehs290]).

Dr. Widimsky and his associates said that they had no disclosures.

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Results Provide Reassurance on Safety

When Dr. James L. Cox introduced the Cox-Maze III procedure for the surgical disruption of atrial fibrillation, the technique involved prolonged cutting and sewing, and the added time on cardiopulmonary bypass and cross-clamping this produced led to a lot of morbidity, including neurologic complications and renal failure.

The current study used a modified Maze procedure that primarily used cryoablation. Because no cutting and sewing were involved, the surgery was much easier, and it produced fewer complications. Surgeons are interested in an atrial fibrillation procedure that is safe and increases the likelihood of leading to sinus rhythm.

This study is important because it shows that this method can be used safely and it improves the end point of resting sinus rhythm. It is paradoxical that the main rhythm benefit was in patients with long-standing persistent atrial fibrillation, because usually that is harder to treat. But this may have been a methodological issue, because they measured the 1-year rhythm outcome without doing prolonged, continuous ECG monitoring. It’s hard to define success in patients with paroxysmal atrial fibrillation unless you monitor patients continuously for a week.

The main message from this study was that the ablation procedure was safe during cardiac surgery and did not add much time or complexity to the surgery. I think these results will increase the use of ablation during cardiac surgery for other reasons. It is a major contribution.
MIGUEL SOUSA UVA, M.D., a cardiac surgeon at Hospital da Cruz Vermelha in Lisbon, made these comments in an interview. He said that he had no disclosures.