Functional and Structural Remodeling as Atrial Fibrillation Progresses in a Persistent Atrial Fibrillation Canine Model

Background

Contractile, electrical, and structural remodeling has been associated with atrial fibrillation (AF), but the progression of functional and structural changes as AF sustains has not been previously evaluated serially.

Objectives

Using a rapid-paced persistent AF canine model, the authors aimed to evaluate the structural and functional changes serially as AF progresses.

Methods

Serial electrophysiological studies in a chronic rapid-paced canine model (n = 19) prior to AF sustaining and repeated at 1, 3, and 6 months of sustained AF were conducted to measure changes in atrial conduction speed and direction. Cardiac late gadolinium enhancement magnetic resonance imaging was performed prior to and following sustained AF to evaluate structural remodeling.

Results

As AF progressed, the overall area of the left atrium with fibrosis increased. Over time, conduction speeds slowed, with speeds decreasing by 0.15 m/s after 3 months and 0.26 m/s after 6 months of sustained AF. Regions that developed fibrosis experienced greater slowing compared with healthy regions (0.32 ± 0.01 m/s decrease vs 0.21 ± 0.01 m/s decrease; P < 0.001). Conduction directions became more aligned (conduction direction heterogeneity decreased from 19.7 ± 0.1° to 17.5 ± 0.1° after 6 months of sustained AF; P < 0.001). Fibrotic regions had a greater decrease in conduction direction heterogeneity (2.7 ± 0.3° vs 2.0 ± 0.2°; P = 0.008).

Conclusions

As AF progressed, functional changes occurred globally throughout the left atrium. Conduction speed slowed, and conduction directions became more aligned over time, with the greatest changes occurring within regions that developed fibrosis.