Mapping Electrical Activation in Atrial Fibrillation

描述(申请人提供)：该项目旨在开发、验证和使用新的标测方法，以加强对心房颤动(AF)兴奋动力学的了解，并改进其治疗。房颤是人类最常见的持续性心律失常，困扰着超过250万美国人，也是导致栓塞性中风的主要原因。对于房颤患者，抗心律失常药物效果不佳，消融治疗通常是唯一可用的治疗方法，但消融治疗的成功率和长期效果存在争议。因此，提高我们对心律失常机制的认识以及如何设计出更好的治疗方法是至关重要的。人们普遍认为，心脏纤颤是一种常见的各种心脏损伤的终末通路，其底物的电生理及其激活模式会发生多因素的改变。同样可以接受的是，促进和控制纤颤的发生和维持的改变具有显著的区域性和患者间的异质性。因此，这项提议的总体目标是开发一套新的作图方法，以提高表征特定于潜在离子非均质的电激活模式的能力。拟议的研究将包括 分离绵羊心脏的全景(全景)心内光学/电子记录和活体绵羊的电子记录。我们将利用我们之前在心脏电活动的荧光内窥镜成像和奇异值分解(SVD)算法方面的进展来设计和测试一种新的方法，该方法最终将能够更好地关联纤颤心房的时空和频率特性，并可能直接适用于个别患者。我们的方法建立在一种新颖的SV分解的基础上，通过对空间、时间和频率相关分量的排序来更好地定位和跟踪潜在的房颤驱动因素。这一数值方案将包括以下三个具体目标：(I)开发越来越详细的中庭计算机模型，以模拟不同的房颤场景，并验证SVD指向驾驶员位置的能力，或者是否存在这样的驾驶员。(Ii)将奇异值分解方法应用于两个完整的羊心心房的全景光学标测数据。全景高分辨率光学标测将作为对心脏电记录进行奇异值分解分析的参考。(Iii)将经过验证的电标测算法应用于绵羊体内的房颤。冷冻消融引起的可逆性心房病变将被用来测试驾驶员的成功定位和房颤的终止。完成研究的目标将为绘制患者的房颤动力学图提供一个坚实的框架，以提高对其的理解和治疗。

DESCRIPTION (provided by applicant): This project aims at developing, validating and using novel mapping approaches to enhance the understanding of excitation dynamics in atrial fibrillation (AF) and to improve its treatment. AF is the most common sustained arrhythmia in humans afflicting more than 2.5 million Americans 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. Thus, advancing our understanding of the mechanisms of the arrhythmia and how to device better therapies for it are of paramount importance. It is generally accepted that fibrillation is a common end-pathway of various insults to the heart with multi-factorial alterations in the electrophysiology of the substrate and its activation patterns. It is also acceptable that the alterations promoting the onset and controlling the maintenance of fibrillation have significant regional as well as inter-patient heterogeneity. It is therefore the general objective of this proposal to develop a set of novel mapping approaches that will improve the capability of characterizing the patterns of electrical activation specific to underlying ionic heterogeneities. The proposed study will include full-view (panoramic) intracardiac optical/electrical recordings in isolated sheep hearts and electrical recordings in-vivo sheep. We will take advantage of our previous developments in fluorescence endoscopic imaging of the electrical activity of the heart and singularity value decomposition (SVD) algorithms to design and test a novel approach that in its final form will enable a better correlation between the space-time and frequency properties of the fibrillating atria, with direct possible applicability to individual patients. Our approach builds on a novel SV factorization into ranked space, time and frequency interrelated components to better localize and track potential drivers of AF. This numerical scheme will be included in 3 specific aims as follows: (i) To develop increasingly detailed computer models of the atria to simulate different AF scenarios and validate the SVD ability to point to a driver location, or whether such a driver exists. (ii) To apply the SVD approach to panoramic optical mapping data from two intact atria of isolated sheep heart. The panoramic high resolution optical mapping will be used as a reference for the SVD analysis performed on electrical intracadiac recordings. (iii) To apply the validated electrical mapping algorithms to AF in-vivo in the sheep. Reversible atrial lesions induced by cryoablation will be used to test successful localization of drivers and termination of AF. Accomplishing the aims of the study will provide a solid framework for mapping AF dynamics in patients to improve its understanding and therapy.