JAMA：心脏起搏器可改善1型肌强直性营养不良患者生存率

3月28日，《美国医学会杂志》（Journal of American Medical Association）发表的一项回顾性队列研究显示，对于心电图提示心脏传导异常的1型肌强直性营养不良患者，置入永久性心脏起搏器与定期监测的非侵入性策略相比，可显著改善患者的生存率。

巴黎Cochin 医院心脏与神经科的Karim Wahbi博士介绍，在中位随访7.4年期间，接受电生理检查并在必要时预防性置入起搏器的患者，死亡率比未接受电生理检查或起搏器置入的患者降低了仅40%。两组间的差异主要在于前者的猝死率更低。这一研究结果提示，传导系统疾病“是可预防性猝死的主要原因之一”。

1型肌强直性营养不良又称Steinert病，是成人中最常见的遗传性神经肌肉疾病，特征性表现是肌无力、肌强直、多重内分泌紊乱、呼吸功能不全，以及心脏异常。约有1/3的患者死于猝死。美国心脏病学会(ACC)和美国心脏协会(AHA)均建议，如果发现1型肌强直性营养不良患者存在完全房室传导阻滞或进展性高级别房室传导阻滞，就应当置入永久性起搏器；如果心电图发现存在1级房室传导阻滞或分支阻滞，建议预防性置入永久性起搏器。但这种侵入性干预措施对于猝死的预防效果，尚未在临床研究中得到验证。

为此，研究者分析了2000~2009年期间参加DM1 Heart注册研究的连续914例1型肌强直性营养不良患者的资料。其中486例的心电图提示轻度传导异常。在这些受试者中，341例接受心脏病专家的建议接受了侵入性干预。对这些患者进行电生理检查发现，164例患者的HV间期超过70 ms，70例患者由心室刺激诱发出了室性快速性心律失常。HV间期超过70 ms的患者置入起搏器(150例)或除颤器(14例)。侵入性干预组的其他患者未置入器械。其余145例患者根据心脏病专家的意见接受非侵入性干预。他们未接受电生理检查，也未置入起搏设备，而是由1名神经病专家和1名心脏病专家(均擅长治疗肌肉疾病)随访1年。共有49例患者使用了抗心律失常药物，包括胺碘酮和β受体阻滞剂。

结果显示，在中位7.4年(0~9.9年)的随访期间，共有80例患者死亡(侵入性干预组50例，非侵入性干预组30例)，即总生存率为74.4%。9年时，两组的生存率分别为76.7%和69.2%。在校正年龄、性别、室上性快速性心律失常病史、左心室射血分数、PR间期、QRS波时限和心率等因素后，侵入性干预组与非侵入性干预组相比，死亡危险比(HR)为0.61。

这一差异主要来源于侵入性干预组的低猝死率：猝死10例，其中8例置入了起搏器、1例置入了除颤器，1例未置入器械)；非侵入性干预组猝死16例。“两组的9年累计猝死发生率分别为4.5%和18.0%。”

两组在呼吸衰竭死亡或其他原因死亡方面则无显著差异。“虽然该研究结果尚需获得其他研究的证实，但目前看来可以考虑对这一猝死风险高的人群采取侵入性干预。”

本项研究由Franaise抗击肌肉疾病协会资助。Wahbi博士报告无相关利益冲突，他的2名同事报告与波士顿科技、法国索林集团、法国Biotronik及健赞公司有联系。（生物谷Bioon.com）

doi:10.1001/jama.2012.346
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Electrophysiological Study With Prophylactic Pacing and Survival in Adults With Myotonic Dystrophy and Conduction System Disease

Karim Wahbi, MD; Christophe Meune, MD; Rapha?l Porcher, PhD; Henri Marc Bécane, MD; Arnaud Lazarus, MD; Pascal Laforêt, MD; Tanya Stojkovic, MD; Anthony Béhin, MD; Hélène Radvanyi-Hoffmann, MD; Bruno Eymard, MD; Denis Duboc, MD

AbstractContext Up to one-third of patients with myotonic dystrophy type 1 die suddenly. Thus far, no intervention has effectively prevented sudden death.

Objective To determine whether an invasive strategy based on systematic electrophysiological studies and prophylactic permanent pacing is associated with longer survival in patients presenting with myotonic dystrophy type 1 and major infranodal conduction delays than a noninvasive strategy.

Design, Setting, and Patients A retrospective study, the DM1 Heart Registry included 914 consecutive patients older than 18 years with genetically confirmed myotonic dystrophy type 1 who were admitted to the Neurological Unit of the Myology Institute of Pitié-Salpêtrière Hospital, a teaching medical center in Paris, France, between January 2000 and December 2009.

Interventions Among 486 patients whose electrocardiogram showed a PR interval greater than 200 milliseconds, a QRS duration greater than 100 milliseconds, or both, the outcome of 341 (70.2%) who underwent an invasive strategy was compared with 145 (29.8%) who underwent a noninvasive strategy. A propensity score risk adjustment and propensity-based matching analysis was used to account for selection biases.

Main Outcome Measures Rates of overall survival (main outcome measure) and sudden death, respiratory death, and other deaths (secondary outcome measures).

Results Over a median follow-up of 7.4 years (range, 0-9.9 years), 50 patients died in the invasive strategy group and 30 died in the noninvasive strategy group (hazard ratio [HR], 0.74 [95 CI, 0.47-1.16]; P = .19), corresponding to an overall 9-year survival of 74.4% (95% CI, 69.2%-79.9%). Regardless of the technique used to adjust for between-group differences in baseline characteristics, the invasive strategy was associated with a longer survival, with adjusted HRs ranging from 0.47 (95% CI, 0.26-0.84; P = .01) for a covariate-adjusted analysis of propensity-matched data to 0.61 (95% CI, 0.38-0.99; P = .047) for an analysis adjusted for propensity score quintiles. The survival difference was largely attributable to a lower incidence of sudden death, which occurred in 10 patients in the invasive strategy group and in 16 patients in the noninvasive strategy group, with HRs ranging from 0.24 (95% CI, 0.10-0.56; P = .001) for an analysis adjusted for propensity score quintiles and covariates to 0.28 (95% CI, 0.13-0.61; P = .001) for an unadjusted analysis of propensity-matched data.

Conclusion Among patients with myotonic dystrophy type 1, an invasive strategy was associated with a higher rate of 9-year survival than a noninvasive strategy.