*Result*: Triggers and maintenance of idiopathic atrial fibrillation: A multiscale computational simulation study.
Original Publication: Amsterdam : Elsevier Science Publishers, c1984-
*Further Information*
*Background and Objective: Idiopathic atrial fibrillation (IAF) is linked to electrical remodeling, yet prospective clinical cohort data isolating the individual contributions of candidate risk factors remain scarce. To address the gap, we used in-silico simulations to delineate the mechanisms and interactions underlying IAF.
Methods: We built a multi-scale atrial computational model on a 3D atrial anatomy integrating ion-channel kinetics, cellular electrophysiology, and tissue-level propagation. Atrial tissue conductivity (ATC), atrial effective refractory period (AERP), and sinus cycle length (SCL) were systematically varied at 6, 4, and 4 levels, respectively, within physiologic ranges. We recorded parameter sets that precipitated IAF and quantified dynamics by complexity, stability, and spatial disorder.
Results: In our simulations, ATC was represented by the diffusion coefficient D <subscript>scalar</subscript> , and the action potential duration at -60 mV (APD-60mV) served as a surrogate for AERP. At SCL = 1000 ms, IAF initiated only when APD-60mV = 94 ms and D <subscript>scalar</subscript> ≤ 0.0002 mm <sup>2</sup> /ms. With SCL shortening, the APD-60mV threshold for initiation decreased. SCL modulated susceptibility but was not sufficient alone. If either the AERP or ATC criterion was unmet, IAF did not initiate at any SCL. After initiation, both slow conduction and high frequency pacing increased arrhythmic complexity (spiral-wave count +63% and +129%); high frequency pacing enhanced stability (spiral-wave lifetimes up to +48%), whereas slow conduction worsened spatial disorder (organization index -27%). Spiral waves preferentially clustered along the interatrial septum.
Conclusions: IAF initiation requires both shortened AERP and reduced ATC, while maintenance is promoted by high-frequency pacing and slowed conduction. The interatrial septum emerges as a leading non-pulmonary-vein source. These findings provide mechanistic insight into IAF initiation and persistence and may inform early prevention.
(Copyright © 2025 Elsevier B.V. All rights reserved.)*
*Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*