Background:A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke.Methods:RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF.Results:In the multivariable model, older age (odds ratio for 10-year increase, 1.99 [95% CI, 1.78–2.23]; P<0.001), hypertension (odds ratio, 1.36 [95% CI, 1.03–1.79]; P=0.0304), diabetes (odds ratio, 0.74 [95% CI, 0.56–0.96]; P=0.022), and body mass index (odds ratio for 5-U increase, 1.29 [95% CI, 1.16–1.43]; P<0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline NT-proBNP (N-terminal prohormone of brain natriuretic peptide) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performance of several published predictive models was assessed, including HAVOC (AF risk score based on hypertension, age ≥75 years, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, and coronary artery disease) and CHA₂DS₂-VASc (stroke risk score based on congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, previous stroke, transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, and sex category [female]) scores, and higher scores were associated with higher rates of developing AF.Conclusions:Besides age, the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after embolic stroke of undetermined source. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

中文翻译：

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来源不明的栓塞性卒中患者房颤发展的预测因素：RE-SPECT ESUS 试验的分析

背景：部分原因不明的栓塞性卒中患者在初步评估后出现无症状心房颤动 (AF) 或发展为 AF。更好地了解发生 AF 的风险对于实施最佳监测策略以预防潜在 AF 引起的复发性卒中至关重要。RE-SPECT ESUS 试验（在二级卒中预防中比较口服凝血酶抑制剂达比加群酯与乙酰水杨酸对不明来源栓塞性卒中患者的疗效和安全性的随机、双盲评估）提供了评估发展为 AF 的预测因子的机会方法：RE-SPECT ESUS 是一项随机对照试验（564 个地点，42 个国家）评估达比加群与阿司匹林在预防不明来源栓塞性卒中患者复发性卒中的效果。在 5390 名入组患者中，中位随访 19 个月，发现 403 名（7.5%）发生 AF，报告为不良事件或根据标准临床护理使用心脏监测。进行单变量和多变量回归分析以定义 AF 的预测因子。结果：在多变量模型中，年龄较大（10 年增加的优势比，1.99 [95% CI，1.78-2.23]；P <0.001）、高血压（优势比，1.36 [95% CI，1.03–1.79]；P = 0.0304）、糖尿病（优势比，0.74 [95% CI，0.56–0.96]；P = 0.022）和体重指数（5-U 增加的优势比，1.29 [95% CI，1.16-1.43]；P <0.001）是研究期间房颤的独立预测因子。在一项针对 1117 名基线 NT-proBNP（脑利钠肽的 N 末端激素原）测量患者的敏感性分析中，只有年龄较大和 NT-proBNP 较高是 AF 的显着独立预测因子。评估了几个已发表的预测模型的性能，包括 HAVOC（基于高血压、年龄≥75 岁、瓣膜性心脏病、外周血管疾病、肥胖、充血性心力衰竭和冠状动脉疾病的 AF 风险评分）和 CHA₂ DS ₂-VASc（基于充血性心力衰竭、高血压、年龄≥75岁[加倍]、糖尿病、既往中风、短暂性脑缺血发作或血栓栓塞[加倍]、血管疾病、年龄65至74岁和性别类别[女性]的卒中风险评分]) 评分，较高的评分与较高的 AF 发生率相关。结论：除了年龄这一最重要的变量外，其他几个因素，包括高血压、较高的体重指数和无糖尿病，是栓塞后 AF 的独立预测因素未确定来源的中风。当基线 NT-proBNP 可用时，只有年龄较大和该生物标志物升高才能预测随后的 AF。了解哪些人患 AF 的风险较高，将有助于识别可能受益于更强烈、长期心脏监测的患者。注册：URL：https://www。临床试验.gov；唯一标识符：NCT02239120。