Sleep Apnea and Hypertrophic Cardiomyopathy - Implications for Arrhythmia and Sudden Death

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Project Description Hypertrophic cardiomyopathy (HCM) is the commonest inherited heart condition. Associated with debilitating refractory symptoms, atrial fibrillation (AF), heart failure (HF) and ventricular arrhythmia (VA), HCM is the leading cause of sudden cardiac death (SCD) in young adults and children. Sleep disordered breathing (SDB), which includes central and obstructive sleep apnea (OSA), has a high prevalence in cardiovascular disease. We and others have shown OSA to be an independent risk factor for AF, HF, nocturnal myocardial infarction and SCD. Our preliminary data suggest that SDB has a high prevalence in patients with HCM and is associated with decreased exercise capacity and AF. While we have shown that OSA is a risk factor for SCD in the general population, its role in HCM-related SCD has never been studied. Apart from our pilot data using gold-standard attended polysomnography (PSG) in patients with HCM, showing a prevalence of OSA greater than 60%, there are no studies using PSG in HCM. We propose to investigate the role of OSA in HCM by: 1) Determining the prevalence, types and severity of SDB in patients with HCM compared with age and sex- matched, normal controls using comprehensive attended PSG. 2) Evaluating the association of OSA and biomarkers of cardiovascular risk including endothelial dysfunction, structural and functional cardiac changes, impaired heart rate variability, and baroreflex dysfunction. 3) Estimating the prevalence ratio for AF in the setting of HCM with and without OSA, and determining the incidence ratio of newly diagnosed AF in the setting of HCM in a prospective longitudinal cohort study. 4) Characterizing the association of OSA with the frequency and day-night variation of VA and sudden death. We hypothesize that OSA has a high prevalence amongst patients with HCM, and is independently associated with refractory symptoms, AF, VA, and SCD. The scientific premise for this proposal builds on several decades of our pioneering work on the cardiovascular consequences of OSA, and our published exploratory studies suggesting undiagnosed SDB is highly prevalent in HCM, and is associated with decreased exercise capacity and increased frequency of AF. Our unpublished pilot data generated for this proposal support our central hypothesis: over 60% of unselected patients with HCM have OSA documented by PSG. The Mayo HCM registry is the largest single-center HCM database in the world with research authorization from 3,673 patients, supporting feasibility of our proposal. Our findings will lead to increased understanding of the role of OSA in symptoms, disease mechanisms, arrhythmia, and SCD, which are the fundamental treatment goals in HCM. This innovative proposal holds significant promise as an elegant and rapidly translatable avenue for improving outcomes in HCM, and will be pivotal in identifying a novel, effective management strategy. These goals directly address the NHLBI mission statement: to promote prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer.