Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting 2.2 million individuals in the United States alone, and is a major cause of morbidity and mortality. Current methods to eliminate AF with anti-arrhythmic drugs and ablation remain suboptimal, reflecting our current lack of understanding of the mechanisms for AF, and how they may differ for patients with presentations such as persistent or paroxysmal AF. This project tests the novel hypothesis that interaction of the dynamic tissue properties of repolarization and conduction with structural heterogeneities provides a direct mechanism for the initiation of human AF and its varying clinical patterns. This project builds upon published work and preliminary observations by our laboratory in patients. We have three specific Aims. 1) To determine whether dynamic tissue properties, including restitution of action potential duration, cause the initiation of atrial fibrillation;2) To determine whether the initiation of atrial fibrillation follows conduction block and reentry;3) To determine whether dynamic tissue properties are required to cause AF in computer models created specifically for each patient, then referenced back to observed AF. We will pursue these aims by acquiring high-resolution electrophysiologic and anatomic data at electrophysiologic study, by performing numerical analysis of activation in both atria, then by developing patient-specific computer models. The computer models that we will create in this project will be among the most detailed and clinically-relevant. This project is significant because it studies a novel mechanism for the development of atrial fibrillation in patients. This mechanism may serve as a method to predict the propensity for AF. Understanding this mechanism may also allow a more rational approach both to drug development and ablation therapy. The performance of this project in patients during electrophysiologic study will also allow its results to be translated directly to practice. Finally, our patient-specific computational models are clinically relevant, and will thus provide a resource for further hypothesis testing in AF.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Rundhaugen, Lynn M
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Miller, John M; Kowal, Robert C; Swarup, Vijay et al. (2014) Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry. J Cardiovasc Electrophysiol 25:921-9
Gonzales, Matthew J; Vincent, Kevin P; Rappel, Wouter-Jan et al. (2014) Structural contributions to fibrillatory rotors in a patient-derived computational model of the atria. Europace 16 Suppl 4:iv3-iv10
McGarry, Thomas J; Narayan, Sanjiv M (2014) Defining arrhythmic risk and defibrillator therapy in ARVC: shocking rhythm? J Am Coll Cardiol 64:126-8
Schricker, Amir A; Lalani, Gautam G; Krummen, David E et al. (2014) Human atrial fibrillation initiates via organized rather than disorganized mechanisms. Circ Arrhythm Electrophysiol 7:816-24
Rostamian, Armand; Narayan, Sanjiv M; Thomson, Louise et al. (2014) The incidence, diagnosis, and management of pulmonary vein stenosis as a complication of atrial fibrillation ablation. J Interv Card Electrophysiol 40:63-74
Schricker, Amir A; Lalani, Gautam G; Krummen, David E et al. (2014) Rotors as drivers of atrial fibrillation and targets for ablation. Curr Cardiol Rep 16:509
Krummen, David E; Hayase, Justin; Morris, David J et al. (2014) Rotor stability separates sustained ventricular fibrillation from self-terminating episodes in humans. J Am Coll Cardiol 63:2712-21
Baykaner, Tina; Lalani, Gautam G; Schricker, Amir et al. (2014) Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM). J Interv Card Electrophysiol 40:237-44
Narayan, Sanjiv M; Baykaner, Tina; Clopton, Paul et al. (2014) Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulat J Am Coll Cardiol 63:1761-8
Trulock, Kevin M; Narayan, Sanjiv M; Piccini, Jonathan P (2014) Rhythm control in heart failure patients with atrial fibrillation: contemporary challenges including the role of ablation. J Am Coll Cardiol 64:710-21

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