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NEJM:研究发现亚临床房颤可增加卒中风险

2012-01-20 MedSci 爱唯医学

近日,国际著名杂志The New England Journal of Medicine在线刊登了国外研究人员的最新研究成果“Subclinical Atrial Fibrillation and the Risk of Stroke,”文章中,研究者发现亚临床房颤可增加卒中风险。 大型国际随机ASSERT研究观察到两个重要结果,一是植入起搏器且无临床房颤(AF)史的老年高血压患者较常出现无

近日,国际著名杂志The New England Journal of Medicine在线刊登了国外研究人员的最新研究成果“Subclinical Atrial Fibrillation and the Risk of Stroke,”文章中,研究者发现亚临床房颤可增加卒中风险。

大型国际随机ASSERT研究观察到两个重要结果,一是植入起搏器且无临床房颤(AF)史的老年高血压患者较常出现无症状的AF发作,并且这些亚临床房性快速心律失常与此后缺血性卒中风险骤升有关;二是采用可编程的算法进行连续心房超速起搏以维持心房起搏,既不能预防临床AF,也不能降低卒中风险[N. Engl. J. Med. 2012;366:120-9]。

该研究由加拿大麦克马斯特大学人口健康研究所的Jeff S. Healey博士及其同事进行,共纳入23个国家的2,580例患者。所有患者的年龄≥65岁,均患有高血压,并且近期曾植入双腔起搏器或植入式心律转复除颤器。入组时无1例患者有AF史。在研究开始时,所有植入起搏器的患者被随机分成2组,一组在该时间段内进行连续心房超速起搏,另一组则关闭这一功能。

在随访的最初3个月内,10.1%的患者发生装置检出的亚临床AF(定义为心房率超过190 次/min,并持续6 min以上)。值得注意的是,该亚组患者至发生这种无症状AF的中位时间为36 d,因此,连续数天的阴性Holter动态心电图监测结果可能是假阴性。最初3个月内出现无症状AF的亚组患者在平均2.5年的前瞻性随访期间发生临床 AF的风险增加5.6倍。此外,最初3个月内出现亚临床AF的患者的缺血性卒中或全身性栓塞发生率为1.7%/年,而该研究中其余患者的发生率为 0.69%/年。

在最初3个月内,无症状AF相关卒中或全身性栓塞的人群归因风险(PAR)为13%,这与Framingham 心脏研究观察到的临床AF相关卒中PAR相似。校正卒中标准预测因素的多因素分析显示,最初3个月内装置检出的亚临床AF与此后卒中风险增加2.5倍独立相关,这可能低估了风险的程度,因为该研究中半数以上的患者基线时接受阿司匹林治疗,并且18%出现早期亚临床AF的患者在随访期间接受华法林治疗,这2种药物显然能够有效降低临床AF患者的卒中风险,但尚不清楚它们是否同样对亚临床AF患者有益。

在CHADS2评分大于2且最初3个月内检出亚临床AF的患者中,缺血性卒中或全身性栓塞发生率为3.7%/年,而在CHADS2评分同样较高但无早期亚临床房性快速心律失常的患者中为0.97%/年。除了10%的患者在随访最初3个月内发生亚临床AF之外,还有另外24%的患者在此后发生亚临床 AF。该研究未对持续时间不足6 min的无症状AF发作进行分类,因此不知道这些发作是否也与此后卒中风险增加有关。另外,心房起搏干预并不影响临床AF的发生率,不过该研究对该预后的检验效能不足。

在随刊述评中,西奈山医疗中心内科主任Gervasio Lamas博士指出,尽管该研究明确表明装置检出的亚临床AF与卒中或外周栓塞年发生率增加2倍以上有关,但以下因果关系问题尚有待解决:这些无症状AF 发作是否确实引发心脏栓塞性卒中,或者它们只是可能反映心肌纤维化或结构性心脏病等卒中风险的标志物而已?值得注意的是,在该研究的最初3个月内,最长亚临床AF发作的时间越长,此后的卒中风险越大。在最长发作持续17.7 h以上的患者中,卒中或全身性栓塞的风险增加了近5倍。Lamas博士表示,除非进一步随机临床研究明确证实对装置检出的AF发作时间较短的患者进行抗凝治疗是合理的,否则其仍将继续依赖于CHADS2评分来决定是否对亚临床AF发作持续数小时的患者实施预防性抗凝治疗。

NEJMoa1105575" target=_blank>doi:10.1056/NEJMoa1105575
PMC:
PMID:

Subclinical Atrial Fibrillation and the Risk of Stroke

Jeff S. Healey, M.D., Stuart J. Connolly, M.D., Michael R. Gold, M.D., Carsten W. Israel, M.D., Isabelle C. Van Gelder, M.D., Alessandro Capucci, M.D., C.P. Lau, M.D., Eric Fain, M.D., Sean Yang, M.Sc., Christophe Bailleul, M.D., Carlos A. Morillo, M.D., Mark Carlson, M.D., Ellison Themeles, M.Sc., Elizabeth S. Kaufman, M.D., and Stefan H. Hohnloser, M.D

BACKGROUND One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. METHODS We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. RESULTS By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. CONCLUSIONS Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.)

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    2015-09-27 asim

    Wait, I cannot fathom it being so staotghifrrward.

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