Characterization of the Electroanatomical Substrate in Human Atrial Fibrillation: The Relationship between Changes in Atrial Volume, Refractoriness, Wavefront Propagation Velocities, and AF Burden

Introduction: Progressive remodeling occurs in experimental models of AF whereby slowing of conduction, shortening of refractoriness, and atrial dilatation are associated with an increased vulnerability to atrial fibrillation (AF). This study investigates the relative changes in atrial geometry and electrophysiology with increasing AF burden in humans. Methods and Results: Patients undergoing ablation of AF or left‐sided accessory pathways were recruited. Atrial volumes were determined by echocardiography. Wavefront propagation velocities (WPV), specifically in the direction of activation, were calculated from pre‐ablation activation (Carto™) maps of both atria. Dispersion, adaptation of, and effective refractoriness (ERP) were measured at 3 sites. A composite arrhythmogenic index (Atrial Volume/WPV × ERP) was derived to compare the degree of electroanatomical remodeling with AF burden. Fifty‐nine patients (22 paroxysmal AF, 19 recurrent persistent AF, and 18 controls) were recruited. AF subjects had slower right atrial WPV (P = 0.01), but no difference in left atrial WPV compared with controls. ERP was reduced globally (P < 0.05), with increased dispersion (P < 0.05). WPV and ERP did not distinguish between patients with paroxysmal or persistent AF. Biatrial volumes were greater only in patients with persistent AF (P < 0.01). There was a stepwise increase in the AI with increasing AF burden (P < 0.0001). Conclusion: An arrhythmogenic substrate exists in human AF, characterized by globally decreased refractoriness with greater dispersion, slower right atrial conduction, and atrial dilatation. Persistence of AF is not accompanied by any further electrical remodeling, but only atrial dilatation. The degree of electroanatomical remodeling is associated with the clinical pattern of AF.