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 肥厚型心肌病（HCM）是最常见的遗传性心脏病。与衰弱有关 难治性症状、心房颤动 (AF)、心力衰竭 (HF) 和室性心律失常 (VA)，HCM 是 年轻人和儿童心源性猝死（SCD）的主要原因。睡眠呼吸障碍（SDB）， 其中包括中枢性和阻塞性睡眠呼吸暂停（OSA），在心血管疾病中发病率很高。 我们和其他人已经证明 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 在 HCM 患者中的患病率很高，并且 与运动能力下降和房颤有关。虽然我们已经证明 OSA 是 SCD 的危险因素 在一般人群中，其在 HCM 相关 SCD 中的作用从未被研究过。除了我们使用的试点数据外 HCM 患者接受多导睡眠图 (PSG) 黄金标准显示 OSA 患病率更高 超过 60%，尚无在 HCM 中使用 PSG 的研究。我们建议通过以下方式研究 OSA 在 HCM 中的作用： 1) 确定 HCM 患者中 SDB 的患病率、类型和严重程度（与年龄和性别相比） 使用全面参与的 PSG 进行匹配的正常对照。 2) 评估 OSA 与心血管风险生物标志物（包括内皮功能障碍）的关联， 心脏结构和功能的变化、心率变异性受损和压力反射功能障碍。 3) 估计伴有或不伴有 OSA 的 HCM 情况下 AF 的患病率，并确定 在一项前瞻性纵向队列研究中，HCM 背景下新诊断 AF 的发生率。 4) 描述 OSA 与 VA 频率和昼夜变化以及猝死之间的关系。 我们假设 OSA 在 HCM 患者中的患病率很高，并且与 具有难治性症状、AF、VA 和 SCD。该提案的科学前提建立在几个基础上 我们数十年来在 OSA 心血管后果方面的开创性工作，以及我们发表的探索性研究 研究表明，未确诊的 SDB 在 HCM 中非常普遍，并且与运动量减少有关 容量和 AF 频率增加。我们为此提案生成的未发布的试点数据支持我们的 中心假设：超过 60% 未经选择的 HCM 患者患有 PSG 记录的 OSA。梅奥 HCM 注册中心是全球最大的单中心 HCM 数据库，拥有 3,673 项研究授权 患者，支持我们建议的可行性。我们的研究结果将有助于加深对 OSA 的症状、疾病机制、心律失常和 SCD，这些是 OSA 的基本治疗目标 肥厚型心肌病。这一创新提案作为一种优雅且可快速转化的途径具有重大前景 改善 HCM 的结果，对于确定新颖、有效的管理策略至关重要。这些 目标直接涉及 NHLBI 的使命宣言：促进心、肺和心肺疾病的预防和治疗 血液疾病并增强所有人的健康，从而延长寿命。