Electrical Activity Patterns in Onset and Cessation of Atrial Fibrillation

项目摘要/摘要 该项目旨在开发、验证和使用新的测绘方法，以增进对 研究早期心房颤动(房颤)的兴奋动力学，以潜在地改善其治疗。AF是一个进步的人 心律失常困扰着250多万美国人和3300万世界各地；它增加了发病的风险 和死亡率，是导致栓塞性中风的主要原因。对于房颤患者，抗心律失常药物具有 不良和消融往往是唯一可用的治疗方法，其成功率和长期影响存在争议。它 被普遍接受的房颤发作是一种短的阵发性发作，会变得更长、更复杂、更多 对时间疗法的挑战。从而提高我们对心律失常发生机制的认识和认识。 如何在它的早期阶段设计出更好的治疗方法是至关重要的。也可以接受的是 促进纤颤发生和调节纤颤维持的改变也具有显著的区域性。 因为患者之间的异质性需要广泛的映射。因此，这项提议的总目标是 开发新的映射方法，以改进对以下联系的潜在机制的表征 引发房颤的全心房电激活模式和异质性的心房基质。建议数 该项目将利用详细的计算机模拟和新的全景心内光学标测 羊心，以及我们在奇异值分解和重构(SVDR)方面的新进展 来检验高动态模式的开始和结束这一普遍假设 可以通过底物的异质性和局部能量分析来预测早期房颤期间的电活动 活动的一部分。我们的具体目标是：(1)在计算模型中演示心房的机制 房颤早期的瞬时激活模式与心电活动的静态能量特性之间的联系 底物和活性。(2)利用一种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、交感神经、迷走神经、迷走神经 牵张诱发绵羊离体心房颤。(3)论证SVDR与能源域 房颤的参数化可以定位干预的靶点，使分离的绵羊心脏发生房颤。 诱导性的。因此，具有最大能量的区域将被实时定位在整个心房和 它们在维持房颤方面的作用将通过局部和可逆的冷冻消融应用来检验。完成我们的任务 AIMS将加强对早期房颤的认识，并为绘制房颤动态图提供坚实的新框架 潜在地改善其治疗方法。

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.