Treatment of Sleep Disordered Breathing in Atrial Fibrillation

描述(由申请人提供)：本申请涉及广泛的挑战领域(04)临床研究，以及特定的挑战主题04-HL-101：确定心肺疾病风险与睡眠呼吸紊乱的联系机制。房颤是美国最常见的持续性心律失常，是血栓栓塞性中风和心力衰竭的危险因素，并与死亡率翻一番有关。尽管使用了潜在的毒性抗心律失常药物和旨在实现正常心律的电复律，但房颤往往是有症状和反复发作的，这一问题引发了人们对替代治疗途径的兴趣，这些途径可能来自对潜在继发性原因的更好管理，如睡眠呼吸障碍。睡眠呼吸障碍(SDB)包括阻塞性睡眠呼吸暂停(OSA)和中枢性睡眠呼吸暂停(CSA)，在心血管疾病的发病机制中非常普遍，包括高血压、心力衰竭和最近的房颤。少量但数量不断增加的观察性研究，其中几项来自我们的实验室，已经表明房颤与OSA和CSA之间存在关联。虽然这种关系的增加无疑激发了人们对SDB(最常见和有效地使用正压(PAP)设备)作为房颤辅助治疗的兴趣，但我们对疾病机制、致病途径以及主要阻塞性或中枢性睡眠呼吸暂停模式的不同影响的认识仍然存在巨大差距。此外，新出现的证据表明，虽然SDB在房颤人群中普遍存在，但通常不伴有主观的日间嗜睡，这是治疗PAP的常见适应症。然而，越来越多的房颤患者被推荐进行昂贵的睡眠评估和治疗，尽管到目前为止，干预试验还没有，留下了关于SDB的作用及其治疗在房颤人群的睡眠和心血管结果中的未解问题。基于我们以前在这一领域的工作，并利用成熟的睡眠和心脏病学基础设施，我们建议进行一项随机对照临床试验，以治疗非嗜睡的房颤患者。利用自适应伺服通气(ASV)，一种对OSA和CSA都有效的较新的PAP设备，我们将测量重要的心血管和睡眠终点，并以复律后房颤复发的时间为主要结果。 公共卫生相关性：该项目研究两种新出现的流行病--房颤(AF)和睡眠呼吸暂停之间的关系。房颤是困扰美国200多万人的最常见的心律失常，与中风、心力衰竭和死亡风险增加有关，并经常与睡眠呼吸暂停一起发生，这表明睡眠呼吸暂停可能是房颤的重要原因。我们的提案将首次确定睡眠呼吸暂停的治疗是否有助于预防房颤的发展。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research, and specific challenge Topic 04-HL-101: Identify Mechanisms Linking Cardiopulmonary Disease Risk and Sleep Disordered Breathing. Atrial fibrillation (AF), the most common sustained arrhythmia in the United States, is a risk factor for thromboembolic stroke and heart failure and has been associated with a doubling of mortality rates. Despite the use of potentially toxic antiarrhythmic drugs and electrical cardioversion designed to achieve normal cardiac rhythm, AF is often symptomatic and recurrent, a problem which has fueled interest in alternative avenues of treatment that may come from better management of potential secondary causes, such as sleep disordered breathing. Sleep disordered breathing (SDB), encompassing both obstructive sleep apnea (OSA) and central sleep apnea (CSA), is highly prevalent and increasingly implicated in the pathogenesis of cardiovascular disease, including hypertension, heart failure, and more recently, AF. A small but increasing number of observational studies, several from our laboratory, have shown an association between AF and both OSA and CSA. While the heightened exposure of this relationship has undoubtedly spurred interest in the treatment of SDB (most often and effectively with positive airway pressure (PAP) devices) as adjunctive therapy of AF, there remain large gaps in our knowledge of disease mechanisms, causal pathways, and the differential effects of a predominant obstructive or central sleep apnea pattern. Furthermore, emerging evidence suggests that, while prevalent in AF populations, SDB is often unaccompanied by subjective daytime sleepiness, the usual indication for PAP treatment. Nevertheless, patients with AF are increasingly referred for costly sleep evaluations and treatment, even though to date, interventional trials are absent, leaving unanswered questions about the role of SDB and its treatment in both sleep and cardiovascular outcomes in the AF population. Building upon our previous work in this area and utilizing a well-established sleep and cardiology infrastructure, we propose a randomized, controlled clinical trial of treatment of SDB in non-sleepy patients with AF. Utilizing adaptive servoventilation (ASV), a newer PAP device effective for treatment of both OSA and CSA, we will measure important cardiovascular and sleep endpoints, with time to AF recurrence after cardioversion the primary outcome. PUBLIC HEALTH RELEVANCE: This project studies the relationship between two emerging epidemics, atrial fibrillation (AF) and sleep apnea. AF, the most common arrhythmia afflicting more than 2 million people in the United States, is associated with stroke, heart failure and an increased risk of death and often occurs together with sleep apnea, suggesting that sleep apnea may be important as a cause of AF. Our proposal will, for the first time, determine whether treatment of sleep apnea helps prevent development of AF.