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）临床研究和特定的挑战主题04-HL-101：确定心脏病风险与睡眠呼吸障碍之间的联系机制。房颤（AF）是美国最常见的持续性心律失常，是血栓栓塞性卒中和心力衰竭的危险因素，并与死亡率加倍相关。尽管使用了潜在毒性的抗心律失常药物和旨在实现正常心律的电复律，但AF通常是症状性和复发性的，这一问题激发了人们对替代治疗途径的兴趣，这些治疗途径可能来自对潜在次要原因（如睡眠呼吸障碍）的更好管理。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），是非常普遍的，并越来越多地涉及心血管疾病的发病机制，包括高血压，心力衰竭，最近，AF。一个小，但越来越多的观察性研究，几个从我们的实验室，已经表明AF和OSA和CSA之间的关联。虽然这种关系的高度暴露无疑激发了对SDB治疗（最常见和有效的是气道正压通气（PAP）设备）作为AF连续治疗的兴趣，但我们对疾病机制、因果通路以及主要阻塞性或中枢性睡眠呼吸暂停模式的差异效应的认识仍存在很大差距。此外，新出现的证据表明，虽然在AF人群中普遍存在SDB，但SDB通常不伴有主观白天嗜睡，这是PAP治疗的常见适应症。尽管如此，越来越多的房颤患者被转诊接受昂贵的睡眠评估和治疗，尽管迄今为止，还没有干预性试验，留下了关于SDB及其治疗在房颤人群中的睡眠和心血管结局中的作用的未回答的问题。基于我们以前在这一领域的工作，并利用完善的睡眠和心脏病学基础设施，我们提出了一项在非睡眠AF患者中治疗SDB的随机对照临床试验。利用自适应伺服通气（ASV），一种有效治疗OSA和CSA的新型PAP设备，我们将测量重要的心血管和睡眠终点，心脏复律后至房颤复发的时间是主要结局。 公共卫生相关性：该项目研究两种新兴流行病，心房颤动（AF）和睡眠呼吸暂停之间的关系。AF是最常见的心律失常，困扰着美国超过200万人，与中风，心力衰竭和死亡风险增加有关，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AF的重要原因。

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.