Electrical Activity Patterns in Onset and Cessation of Atrial Fibrillation

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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.