Mapping Electrical Activation in Atrial Fibrillation

描述（由申请人提供）：本项目旨在开发、验证和使用新型标测方法，以增强对心房颤动（AF）兴奋动力学的理解并改善其治疗。AF是人类最常见的持续性心律失常，困扰着超过250万美国人，是栓塞性中风的主要原因。对于房颤患者，抗心律失常药物的效果不佳，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。因此，提高我们对心律失常发生机制的认识以及如何设计更好的治疗方法是至关重要的。一般认为，纤维性颤动是对心脏的各种损伤的常见终末途径，具有底物的电生理学及其激活模式的多因素改变。促进纤颤发作和控制纤颤维持的改变具有显著的区域和患者间异质性也是可以接受的。因此，这是本提案的总体目标，开发一套新的映射方法，将提高表征特定的潜在离子异质性的电激活模式的能力。拟议的研究将包括 离体绵羊心脏的全视图（全景）心内光学/电记录和活体绵羊的电记录。我们将利用我们以前在心脏电活动的荧光内窥镜成像和奇异值分解（SVD）算法中的发展来设计和测试一种新的方法，该方法的最终形式将使心房的时空和频率特性之间具有更好的相关性，直接适用于个体患者。我们的方法建立在一种新的SV分解为排名空间，时间和频率相关的组件，以更好地定位和跟踪AF的潜在驱动程序。该数值方案将包括在以下3个具体目标：（i）开发越来越详细的心房计算机模型，以模拟不同的AF场景，并验证SVD指向驱动程序位置的能力，或者是否存在这样的驱动程序。(ii)应用奇异值分解（SVD）方法对离体绵羊心脏两个完整心房的全景光学标测数据进行处理。全景高分辨率光学标测将用作对电腔内记录进行SVD分析的参考。(iii)将经确认的电标测算法应用于绵羊体内AF。冷冻消融诱导的可逆性心房病变将用于测试驱动器的成功定位和AF的终止。实现研究的目的将为标测患者的AF动力学提供坚实的框架，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.