Heart Rate Fragmentation: New Biomarker of Atrial Fibrillation Risk

心率碎片：心房颤动风险的新生物标志物

• 批准号: 10215280
• 负责人: Madalena D Costa
• 金额: $ 58.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-10 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215280
• 关键词: Age; Ambulatory Electrocardiography; Arrhythmia; Atherosclerosis Risk in Communities; Atrial Fibrillation; Biological Markers; Blood coagulation; Brain; Cardiac; Cardiac health; Cardioscopes; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Clinical; Cohort Studies; Data; Defibrillators; Dementia; Development; Electrophysiology (science); Embolism; Frequencies; Goals; Heart Abnormalities; Heart Atrium; Heart Diseases; Heart Rate; Heart failure; Hour; Impaired cognition; Implant; Individual; Ischemia; Left; Left Atrial Function; Left Ventricular Ejection Fraction; Left Ventricular Mass; Left atrial structure; Link; Magnetic Resonance Imaging; Measurement; Measures; Modeling; Monitor; Multi-Ethnic Study of Atherosclerosis; Myopathy; National Heart, Lung, and Blood Institute; Neurologic; Pacemakers; Participant; Patients; Plant Roots; Population; Prevention; Process; Public Health; Regulation; Research; Research Project Grants; Risk; Risk Factors; Sinoatrial Node; Sleep; Stroke; Structure; Symptoms; Technology; Ventricular; Work; cardiovascular disorder risk; cardiovascular health; clinical care; cognitive function; cognitive testing; embolic stroke; heart electrical activity; heart function; heart rate variability; heart rhythm; indexing; member; monitoring device; offspring; precision medicine; prospective; stroke risk; structural heart disease; tool

PROJECT SUMMARY / ABSTRACT Atrial fibrillation (AF), a common arrhythmia, is associated with substantially elevated risks of stroke, cognitive decline, dementia, arterial emboli, heart failure, and cardiovascular death. Existing studies of AF generally investigate AF that has been clinically recognized, but studies in patients with implanted monitoring devices such as pacemakers or defibrillators indicate that a large proportion of AF episodes produce no symptoms at all and are undetected clinically. Furthermore, complications commonly attributed to AF, including embolic stroke, often occur in individuals with alterations of left atrial structure and function (atrial myopathy) but in the absence of clinically recognized AF. Therefore, clinical presentation with AF may represent a late stage in the pathophysiologic process linking atrial myopathy with serious complications including stroke and cognitive decline. New biomarkers are needed that reflect atrial myopathy and are highly predictive of AF and its complications. In the proposed research project, we will study newly developed heart rate (HR) fragmentation metrics computed from long-term electrocardiographic (ECG) recordings. Our preliminary data support the hypothesis that these new HR fragmentation metrics, developed by members of our investigative team, reflect breakdown of the neuroautonomic-electrophysiologic network controlling the sino-atrial node and its regulation of heart rate, and are highly predictive of both AF and cognitive impairment. In the setting of the Multi-Ethnic Study of Atherosclerosis (MESA), we propose to compute HR fragmentation indices from overnight ECG recordings and determine the association of HR fragmentation with cardiac structure assessed by MRI, with incident AF, and with brain structure and function assessed by MRI and cognitive testing. In exploratory analyses, we will use data from 14-day ambulatory ECG monitors to determine the short-term relationship of paroxysmal AF with HR fragmentation. Data from the Sleep Heart Health Study cohorts will be used to replicate findings from MESA for our primary aim. Our research will determine the extent to which HR fragmentation is a biomarker of altered left atrial structure and function, clinically recognized AF, and neurological complications of AF including impaired cognitive function and microvascular ischemia. With recent developments in mobile monitoring technology, noninvasive ambulatory ECG monitoring overnight or for longer periods is now practical. The measurement of HR fragmentation from these ECG recordings can be automated. Thus, if HR fragmentation is indeed a biomarker of atrial myopathy, AF, and its complications, information from noninvasive ECG monitoring may inform clinical care, including decisions about therapy to reduce the risk of stroke.

项目概要/摘要 心房颤动 (AF) 是一种常见的心律失常，与中风、认知障碍和认知障碍的风险显着升高相关。 衰退、痴呆、动脉栓塞、心力衰竭和心血管死亡。 AF 的现有研究总体 研究已被临床认可的房颤，但研究对象是植入监测设备的患者 例如起搏器或除颤器表明，大部分 AF 发作在 所有这些都在临床上未被发现。此外，房颤常见的并发症包括栓塞 中风通常发生在左心房结构和功能改变（心房肌病）的个体中，但 缺乏临床公认的房颤。因此，房颤的临床表现可能代表了该病的晚期阶段。 心房肌病与中风和认知等严重并发症相关的病理生理过程 衰退。需要新的生物标志物来反映心房肌病并高度预测 AF 及其相关疾病 并发症。在拟议的研究项目中，我们将研究新开发的心率（HR）碎片 根据长期心电图 (ECG) 记录计算得出的指标。我们的初步数据支持 假设我们的调查团队成员开发的这些新的人力资源分散指标反映了 控制窦房结的神经自主电生理网络的崩溃及其调节 心率，并且高度预测 AF 和认知障碍。在多民族背景下 动脉粥样硬化 (MESA) 研究，我们建议根据夜间心电图计算 HR 碎片指数 记录并确定 HR 碎片与 MRI 评估的心脏结构的关联， AF 事件，并通过 MRI 和认知测试评估大脑结构和功能。处于探索之中 分析中，我们将使用 14 天动态心电图监测仪的数据来确定以下因素的短期关系： 阵发性 AF 伴 HR 碎片。睡眠心脏健康研究队列的数据将用于 复制 MESA 的研究结果以实现我们的主要目标。我们的研究将决定人力资源的程度 碎裂是左心房结构和功能改变的生物标志物、临床公认的 AF 和 房颤的神经系统并发症包括认知功能受损和微血管缺血。随着最近 移动监测技术、夜间或更长时间无创动态心电图监测的发展 时期现已实用。从这些心电图记录中测量心率碎片可以是 自动化。因此，如果 HR 碎片确实是心房肌病、房颤及其并发症的生物标志物， 来自无创心电图监测的信息可以为临床护理提供信息，包括有关治疗的决策 降低中风的风险。