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

睡眠呼吸暂停和肥厚性心肌病 - 对心律失常和猝死的影响

• 批准号: 9216117
• 负责人: Virend K Somers
• 金额: $ 78.59万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9216117
• 关键词: Address; Aerobic; Affect; Age; American; Apnea; Arrhythmia; Atrial Fibrillation; Authorization documentation; Baroreflex; Biological Markers; Cardiac; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Child; Clinical; Data; Databases; Defibrillators; Diagnosis; Diastolic blood pressure; Disease; Frequencies; Functional disorder; General Population; Genetic Screening; Goals; Gold; Guidelines; Health; Heart; Heart Atrium; Heart Diseases; Heart Rate; Heart failure; Hematological Disease; High Prevalence; Hypertrophic Cardiomyopathy; Impairment; Implantable Defibrillators; Incidence; Individual; Inherited; Injury; Laboratories; Lead; Left; Longitudinal cohort study; Lung diseases; Mission; Morbidity - disease rate; Myocardial; Myocardial Infarction; National Heart, Lung, and Blood Institute; Newly Diagnosed; Obstructive Sleep Apnea; Oxygen; Patients; Polysomnography; Prevalence; Prevention; Publishing; Recovery; Refractory; Registries; Research; Resistance; Risk; Risk Factors; Role; Severities; Shock; Sleep Apnea Syndromes; Stress; Sudden Death; Symptoms; Tachycardia; Testing; Variant; Ventricular Arrhythmia; Work; cardiovascular risk factor; endothelial dysfunction; exercise capacity; heart function; heart rate variability; improved outcome; indexing; innovation; mortality; novel; prospective; screening; sex; sudden cardiac death; tool; young adult

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.

项目描述 肥厚的心肌病（HCM）是最常见的遗传心脏病。与虚弱有关 难治性症状，心房颤动（AF），心力衰竭（HF）和心室心律不齐（VA），HCM是 年轻人和儿童的心脏突然死亡（SCD）的主要原因。睡眠不足的呼吸（SDB）， 其中包括中枢和阻塞性睡眠呼吸暂停（OSA）在心血管疾病中患病率很高。 我们和其他人已显示OSA是AF，HF，夜间心肌梗塞的独立危险因素 和SCD。我们的初步数据表明，SDB患有HCM患者的患病率很高，IS 与运动能力和AF的降低相关。虽然我们已经证明OSA是SCD的危险因素 在一般人群中，从未研究过其在与HCM相关的SCD中的作用。除了使用我们的飞行员数据 黄金标准参加了HCM患者的多个学术表（PSG），显示出OSA的患病率更高 超过60％，在HCM中没有使用PSG的研究。我们建议研究OSA在HCM中的作用： 1）与年龄和性别相比，确定HCM患者SDB的患病率，类型和严重程度 使用全面参加的PSG匹配的正常对照。 2）评估OSA与心血管风险的生物标志物的关联，包括内皮功能障碍， 结构和功能性心脏变化，心率变异性受损以及压力反射功能障碍。 3）估计在有和没有OSA的HCM设置中，AF的患病率率，并确定 在前瞻性纵向队列研究中，在HCM的情况下，新诊断的AF的发生率比。 4）表征OSA与VA和猝死的频率和夜晚变化的关系。 我们假设OSA在HCM患者中的患病率很高，并且独立相关 具有难治性症状，AF，VA和SCD。该提案的科学前提是基于几个 我们关于OSA心血管后果的开创性工作数十年，我们已发表的探索性 提示未诊断SDB的研究在HCM中非常普遍，并且与运动减少有关 容量和AF的频率增加。我们为此提案生成的未发表的试点数据支持我们 中央假设：超过60％的未选择的HCM患者已由PSG记录。蛋黄酱 HCM注册表是世界上最大的单中心HCM数据库，其研究授权为3,673 患者，支持我们的提议的可行性。我们的发现将导致人们对 症状，疾病机制，心律不齐和SCD的OSA，这是 HCM。这项创新的提案具有巨大的希望，是一种优雅且迅速翻译的途径 改善HCM的结果，并将在确定一种新颖的有效管理策略方面至关重要。这些 目标直接解决NHLBI使命声明：促进心脏，肺和治疗 血液疾病并改善所有人的健康，以便他们的寿命更长。