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.
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.
| Mansukhani, Meghna Prabhdas; Calvin, Andrew Donald; Kolla, Bhanu Prakash et al. (2013) The association between atrial fibrillation and stroke in patients with obstructive sleep apnea: a population-based case-control study. Sleep Med 14:243-6 |
| Mansukhani, Meghna P; Allison, Thomas G; Lopez-Jimenez, Francisco et al. (2013) Functional aerobic capacity in patients with sleep-disordered breathing. Am J Cardiol 111:1650-4 |
| Albuquerque, Felipe N; Calvin, Andrew D; Sert Kuniyoshi, Fatima H et al. (2012) Sleep-disordered breathing and excessive daytime sleepiness in patients with atrial fibrillation. Chest 141:967-973 |
| Krause, Megan L; Patch, Richard K; Caples, Sean M (2012) A 36-year-old man with seizures and multiple cystic pulmonary nodules. Chest 142:256-259 |
| Calvin, Andrew D; Caples, Sean M (2011) Getting to the heart of sleep deprivation. Sleep 34:251-2 |
| Ramar, Kannan; Caples, Sean M (2010) Cardiovascular consequences of obese and nonobese obstructive sleep apnea. Med Clin North Am 94:465-78 |
| Romero-Corral, Abel; Caples, Sean M; Lopez-Jimenez, Francisco et al. (2010) Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest 137:711-9 |
| Konecny, Tomas; Kuniyoshi, Fatima H Sert; Orban, Marek et al. (2010) Under-diagnosis of sleep apnea in patients after acute myocardial infarction. J Am Coll Cardiol 56:742-3 |
