Electrical Activity Patterns in Onset and Cessation of Atrial Fibrillation

心房颤动发作和停止时的电活动模式

• 批准号: 10597215
• 负责人: OMER BERENFELD
• 金额: $ 59.39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-25 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597215
• 关键词: Ablation; Acceleration; Algorithms; American; Anatomy; Anti-Arrhythmia Agents; Appearance; Area; Arrhythmia; Atrial Fibrillation; Automobile Driving; Characteristics; Clinical; Collection; Complex; Computer Models; Computer Simulation; Cryosurgery; Data; Development; Devices; Endocardium; Epicardium; Frequencies; Future; Heart; Heart Atrium; Heterogeneity; Histology; Individual; Intervention; Investigation; Lead; Link; Long-Term Effects; Maintenance; Maps; Methods; Modality; Modeling; Morbidity - disease rate; Nature; Optics; Patients; Pattern; Persons; Play; Population; Prevalence; Property; Proteomics; Risk; Role; Sheep; Sinus; Site; Solid; Stretching; Tachycardia; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; computerized data processing; electrical property; embolic stroke; human data; human model; improved; mortality; novel; pharmacologic; prevent; reconstruction; risk stratification; sheep model; structural determinants; success

PROJECT SUMMARY/ABSTRACT This project aims at developing, validating and using novel mapping approaches to enhance the understanding of excitation dynamics in early atrial fibrillation (AF) to potentially improve its treatment. AF is a progressive arrhythmia afflicting more than 2.5 million Americans and 33 million worldwide; it increases risks for morbidity and mortality and is the leading cause of embolic stroke. For patients with AF, anti-arrhythmic drugs perform poorly and ablation, with controversial success rate and long-term effects, is often the only therapy available. It is generally accepted AF initiates as short paroxysmal episodes that get prolonged, more complex and more challenging for therapy with time. Thus, advancing our understanding of the mechanisms of the arrhythmia and how to device better therapies for it at its very early stage are of paramount importance. It is also accepted that the alterations promoting the onset and regulating the maintenance of fibrillation have significant regional as well as inter-patient heterogeneity requiring extensive mapping. It is therefore the general objective of this proposal to develop novel mapping approaches to improve characterization of mechanisms underlying the link between atria-wide patterns of electrical activation initiating AF and the heterogeneous atrial substrate. The proposed project will utilize detailed computer simulations and novel panoramic intracardiac optical mapping in isolated sheep hearts, together with our new developments in singular value decomposition and reconstruction (SVDR) of hierarchical energy modes, to test the general hypothesis that onset and cessation of highly dynamic patterns of electrical activity during early AF can be predicted by the substrate heterogeneity and by local energy analysis of the activity. Our specific aims are: (1) To demonstrate in computational models of the atria the mechanistic links between transient activation patterns during early AF and the stationary energetic properties of the substrate and activity. (2) To utilize a novel panoramic optical mapping and SVDR algorithms to demonstrate the characteristics of dynamical activation patterns during initiation and early stabilization of sympathetic, vagal, and stretched induced AF in the sheep isolated heart. (3) To demonstrate that SVDR and energy domain parametrization of AF can localize targets for interventions to render the AF in the isolated sheep hearts non- inducible. Accordingly, regions with maximal energy will be localized in the real-time across the entire atria and their role in sustaining the AF will be tested by local and reversible cryo-ablation applications. Accomplishing our aims will enhance understanding of early AF and provide solid new framework for mapping AF dynamics in patients to potentially improve its therapy.

项目概要/摘要 该项目旨在开发、验证和使用新颖的绘图方法来增强理解 早期心房颤动（AF）的兴奋动力学，有可能改善其治疗。 AF 是渐进式 心律失常困扰着超过 250 万美国人和 3300 万全世界患者；它增加了发病风险 和死亡率，是栓塞性中风的主要原因。对于 AF 患者，抗心律失常药物可以发挥作用 消融治疗的成功率和长期效果存在争议，但往往是唯一可用的治疗方法。它 人们普遍认为房颤是由短暂的阵发性发作引起的，随后会变得更长、更复杂、更严重。 随着时间的推移，治疗具有挑战性。因此，增进我们对心律失常机制的理解 如何在其早期阶段为其提供更好的治疗方法至关重要。还公认的是 促进颤动发生和调节维持颤动的改变也具有显着的区域性 由于患者间的异质性需要广泛的绘图。因此，本提案的总体目标是 开发新颖的绘图方法，以改善对之间联系的机制的描述 心房范围内电激活启动 AF 的模式和异质心房基质。拟议的 该项目将在隔离中利用详细的计算机模拟和新颖的全景心内光学测绘 羊心，以及我们在奇异值分解和重构（SVDR）方面的新进展 分层能量模式，以检验高度动态模式的开始和停止的一般假设 早期 AF 期间的电活动可以通过基质异质性和局部能量分析来预测 的活动。我们的具体目标是：（1）在心房的计算模型中证明机械 早期 AF 期间的瞬态激活模式与静态能量特性之间的联系 底物和活性。 (2) 利用新颖的全景光学测绘和SVDR算法进行演示 交感神经、迷走神经的启动和早期稳定过程中动态激活模式的特征 并在绵羊离体心脏中拉伸诱发房颤。 (3) 证明SVDR和能量域 AF 的参数化可以定位干预目标，使离体羊心脏中的 AF 不发生变化。 可诱导的。因此，具有最大能量的区域将实时定位在整个心房中，并且 它们在维持房颤方面的作用将通过局部和可逆冷冻消融应用进行测试。完成我们的 目标将增强对早期 AF 的理解，并为绘制 AF 动态提供坚实的新框架 患者可能会改善其治疗。