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: 10442503
• 负责人: Madalena D Costa
• 金额: $ 58.94万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442503
• 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; cardiac magnetic resonance imaging; 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; 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.

项目总结/摘要 心房颤动（AF）是一种常见的心律失常，与卒中、认知功能障碍、 衰退、痴呆、动脉栓塞、心力衰竭和心血管死亡。现有的AF研究一般 研究已被临床识别的房颤，但在植入监测器械的患者中进行研究 例如起搏器或除颤器，表明大部分AF发作在 所有这些都是临床上无法检测到的。此外，通常归因于AF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的个体（心房肌病），但在 因此，AF的临床表现可能代表AF的晚期阶段， 心房肌病与严重并发症（包括中风和认知功能障碍）相关的病理生理过程 下降需要新的生物标志物来反映心房肌病变，并高度预测AF及其 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）记录计算的指标。我们的初步数据支持 假设这些新的人力资源碎片化指标，由我们的调查团队成员开发，反映了 控制窦房结的神经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（梅萨）的研究，我们建议从夜间心电图计算HR碎片指数 记录并确定HR碎片与MRI评估的心脏结构的相关性， 事件AF，并通过MRI和认知测试评估大脑结构和功能。的在试探性 分析，我们将使用14天动态心电图监测数据，以确定短期关系， 阵发性房颤伴心率碎裂。来自睡眠心脏健康研究队列的数据将用于 复制梅萨的发现来实现我们的主要目标。我们的研究将决定人力资源部门在多大程度上 碎裂是左心房结构和功能改变、临床识别的AF和 AF的神经系统并发症，包括认知功能受损和微血管缺血。与最近 移动的监测技术、夜间或更长时间的无创动态心电图监测的发展 现在，时间是实际的。可以从这些ECG记录测量HR碎片。 自动的因此，如果HR碎裂确实是心房肌病变、AF及其并发症的生物标志物， 无创心电图监测的信息可以为临床护理提供信息，包括有关治疗的决定， 降低中风的风险。