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.

项目摘要/摘要 该项目旨在开发，验证和使用新颖的映射方法来增强理解 早期房颤（AF）中激发动力学的可能改善其治疗方法。 AF是一个进步的 心律失常困扰着超过250万美国人和全球3300万人；它增加了发病率的风险 和死亡率，是栓塞中风的主要原因。对于AF患者，抗心律失常药物会执行 唯一可用的疗法，较差，消融率很高，具有有争议的成功率和长期影响。它 被普遍接受的AF启动是短时间延长，更复杂且更多的短阵发性发作 随着时间的流逝而挑战治疗。因此，促进我们对心律不齐机制的理解和 如何在早期阶段为其设备更好的疗法至关重要。也接受 促进发作和调节纤颤的变化也具有显着的区域性 作为患者间的异质性，需要大量映射。因此，这是该提议的一般目标 开发新型的映射方法，以改善对联系的机制的表征 范围内的电动激活模式启动AF和异质性心房底物。提议 项目将利用详细的计算机模拟和新颖的全景内光学映射 绵羊的心，以及我们在奇异价值分解和重建方面的新发展（SVDR） 分层能量模式，以检验一般假设，即发作和停止高度动态模式 早期AF期间的电活动可以通过底物异质性和局部能量分析来预测 活动。我们的具体目的是：（1）在心房的计算模型中演示机械 早期AF期间瞬时激活模式与固定能量的链接 底物和活动。 （2）利用新颖的全景光学映射和SVDR算法来证明 在启动和早期稳定交感神经，迷走神经，迷走神经， 并在绵羊孤立的心脏中伸展诱导的AF。 （3）证明SVDR和能量域 AF的参数化可以将目标定位以使AF在孤立的绵羊心脏中呈现AF 诱导。因此，具有最大能量的区域将在整个心房的实时定位，并且 它们在维持AF中的作用将由本地和可逆的冷冻燃料应用测试。完成我们的 目的将增强对早期AF的理解，并为绘制AF动态绘制AF动态提供扎实的新框架 患者有可能改善其治疗。