Electrical Activity Patterns in Onset and Cessation of Atrial Fibrillation

项目概要/摘要 该项目旨在开发、验证和使用新的映射方法，以增强对 早期心房颤动（AF）的兴奋动力学，以潜在地改善其治疗。AF是一种渐进的 心律失常折磨超过250万美国人和3300万世界各地;它增加了发病率的风险 和死亡率，是栓塞性中风的主要原因。对于房颤患者，抗心律失常药物 消融术的成功率和长期效果存在争议，通常是唯一可用的治疗方法。它 一般认为，房颤最初是短暂的阵发性发作，随后会延长，变得更复杂， 随着时间的推移，治疗面临挑战。因此，推进我们对心律失常机制的理解， 如何在其早期阶段设计更好的治疗方法至关重要。人们还认为， 促进纤颤发生和调节纤颤维持的改变也具有明显的区域性 因为患者间的异质性需要广泛的映射。因此，本建议的总体目标是 开发新的映射方法，以改善对以下联系的机制的表征： 全心房电激活模式引发AF和异质性心房基质。拟议 该项目将利用详细的计算机模拟和新颖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 的层次能量模式，以测试的一般假设，发病和停止的高度动态模式， 早期AF期间的电活动可以通过基底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， 在早期AF期间的瞬时激活模式与心房肌的稳态能量特性之间的联系 底物和活性。(2)利用一种新的全景光学映射和SVDR算法， 在交感神经，迷走神经， 牵张诱发羊离体心脏房颤。(3)为了证明SVDR和能量域 AF的参数化可以定位干预的靶点，以使离体绵羊心脏中的AF不受影响。 可诱导的因此，具有最大能量的区域将在整个心房上实时定位， 它们在维持AF中的作用将通过局部和可逆的冷冻消融应用进行测试。实现我们 aims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。

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.