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，以及具体的挑战主题04- hl -101：识别心肺疾病风险和睡眠呼吸障碍的联系机制。房颤（AF）是美国最常见的持续性心律失常，是血栓栓塞性中风和心力衰竭的危险因素，与死亡率增加一倍有关。尽管使用了具有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，但房颤通常是有症状的和反复发作的，这一问题激起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），是非常普遍的，并且越来越多地涉及心血管疾病的发病机制，包括高血压、心力衰竭和最近的房颤。我们实验室的一些观察性研究显示房颤与OSA和CSA之间存在关联。虽然这种关系的高度曝光无疑激发了对SDB治疗的兴趣（最常见和有效的是使用气道正压通气（PAP）装置）作为房颤的辅助治疗，但我们对疾病机制，因果途径以及主要阻塞性或中央性睡眠呼吸暂停模式的差异影响的了解仍然存在很大差距。此外，新出现的证据表明，虽然在房颤人群中普遍存在，但SDB通常不伴有主观的白天嗜睡，这是PAP治疗的通常适应症。尽管如此，房颤患者越来越多地接受昂贵的睡眠评估和治疗，尽管迄今为止，没有介入试验，关于SDB及其治疗在房颤人群睡眠和心血管结局中的作用的问题仍未得到解决。基于我们之前在该领域的工作，并利用完善的睡眠和心脏病学基础设施，我们提出了一项随机对照临床试验，用于治疗房颤非困倦患者的SDB。利用适应性伺服通气（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，以心律转复后房颤复发的时间为主要终点。

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.