Atrial fibrillation: Physiologic characteristics and assessment of organization to optimize therapeutic modalities

Introduction. Atrial fibrillation (AF) is a common disease that is associated with an increased risk of stroke and mortality, impaired exercise tolerance, fatigue, and heart failure. In order to optimize the current therapeutic strategies, it is critical to understand the anatomy and electrophysiology of AF wavelets.; Specific aims. Specific Aim #1 - to assess the relative contributions of electrical and morphological remodeling to AF propagation and vulnerability. Specific Aim #2 - to develop an algorithm that would measure the organization of AF using frequency domain analysis of a wide bipolar atrial electrogram (organization index (OI)). Specific Aim #3 - to use the OI metric to increase defibrillation efficacy. Specific Aim #4 - to use the OI metric to increase the efficacy of burst pace termination of AF. Specific Aim #5 - to use the OI metric to optimize the timing of electrical cardioversion (CV) shock delivery in patients. Specific Aim #6 - to use frequency domain analysis to study the spatiotemporal organization in the transition from acute to chronic AF.; Methods and results. Specific Aim #1 - A chronic AF model was developed in 8 dogs by creating mitral regurgitation and rapid atrial pacing. Specific Aim #2 - AF was initiated with burst atrial pacing in 10 dogs. The atrial defibrillation threshold (ADFT50) was determined, and defibrillation was repeated at the ADFT50. Specific Aim #3 - 15 dogs were conditioned with rapid atrial pacing for 48 hours. Wide bipolar electrograms were digitally filtered and a FFT was performed over a sliding 2-second window. Specific Aim #4 - Nine dogs were conditioned with rapid atrial pacing for 48 hours. The OI was calculated as described above. Specific Aim #5 - Large surface area electrograms were recorded in patients undergoing electrical cardioversion for AF. Specific Aim #6 - A 64-electrode basket catheter was placed in the LA in dogs with either chronic AF or after 48 hours of pacing (acute). A single dominant frequency was identified in all of bipoles in acute AF and in only a fraction of the bipoles in chronic AF.; Conclusion. In this model of chronic AF it appears that vulnerability to AF is more dependent on persisting structural abnormalities than electrophysiological abnormalities. These structural abnormalities also appear to play a role in the loss of the spatiotemporal organization from acute to chronic AF. (Abstract shortened by UMI.)...