Mapping Electrical Activation in Atrial Fibrillation

描述（由申请人提供）：本项目旨在发展，验证和使用新的绘图方法来增强对房颤（AF）兴奋动力学的理解并改善其治疗。房颤是人类最常见的持续性心律失常，折磨着超过250万美国人，是栓塞性中风的主要原因。对于房颤患者，抗心律失常药物效果不佳，而消融通常是唯一可用的治疗方法，其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理解以及如何为心律失常设计更好的治疗方法至关重要。人们普遍认为，纤维性颤动是各种心脏损伤的共同终末通路，其底物的电生理及其激活模式发生多因素改变。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，这也是可以接受的。因此，本提案的总体目标是开发一套新的映射方法，以提高表征特定于潜在离子异质性的电激活模式的能力。拟议的研究将包括

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.