ELECTROPHYSIOLOGICAL AND STRUCTURAL REMODELING IN PATIENTS WITH CHRONIC ATRIAL FIBRILLATION

Abstract

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, with increasing global burden driven by aging populations and limited efficacy of current therapies in advanced disease stages. Progressive atrial remodeling is central to AF initiation, maintenance, and chronicity, yet its integrated electrophysiological, structural, and molecular dynamics remain incompletely defined. This study employed a mixed-methods experimental design combining high-resolution atrial electrophysiological mapping, quantitative molecular profiling, structural imaging, and qualitative histopathological assessment. Multivariate modeling and advanced visualization techniques were applied to characterize remodeling-associated changes and their contribution to AF persistence. The findings demonstrate marked electrical remodeling characterized by shortened excitation wavelength, increased refractory dispersion, and conduction heterogeneity. Structural remodeling manifested as spatially heterogeneous atrial fibrosis with nonlinear escalation beyond defined thresholds. Molecular analyses revealed significant calcium-handling instability, oxidative stress amplification, inflammatory signaling activation, and profibrotic pathway engagement, all of which correlated strongly with electrophysiological instability. Integrated multivariate analyses outperformed single-domain metrics in predicting AF maintenance. Sex-specific remodeling patterns were observed, indicating differential electrophysiological–structural coupling.AF persistence emerges from synergistic, multiscale remodeling processes rather than isolated triggers. These results support a shift toward substrate-targeted and personalized therapeutic strategies aimed at interrupting remodeling cascades and preventing disease progression