Abstract
<jats:p>Background Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery with POAF susceptibility thought to be primarily the result of pre-existing structural atrial disease, specifically fibrosis. We tested this hypothesis directly by combining preoperative imaging of atrial fibrosis with continuous physiological monitoring before POAF onset. Methods This prospective single center study (2023?2025) comprised 6,697 adults without prior atrial fibrillation (AF) undergoing elective cardiac surgery. Subjects were enrolled into three prespecified, non-overlapping cohorts: a mechanistic imaging cohort (n=52) to test whether preoperative atrial fibroblast activation predicts POAF; a physiological monitoring cohort (n=3,183) to characterize peri-event autonomic dynamics via time-resolved HRV analysis; and an independent prospective observability cohort (n=3,451) for validation. The prespecified primary analyses assessed time-domain and frequency-domain HRV across six consecutive 10-minute intervals during the 60 minutes preceding POAF onset. Generalized estimating equations models were applied. Results Preoperative atrial fibroblast activation did not differ significantly between patients with (n=22) or without POAF (n=52). By contrast, in a physiological monitoring cohort (n=3,183), time-resolved heart rate variability analysis revealed progressive autonomic destabilization beginning approximately 20 minutes before POAF onset, with significant divergence in heart-rate-corrected SDNN in the final 10-minute pre-event interval (marginal mean difference 0.0139, 95% CI 0.0113?0.0164; P<0.001; Cohen's d=0.728). This signal was independently validated in a prospective observability cohort (n=3,451), achieving fragment-level sensitivity of 69.6% and specificity of 97.5% at the 10-minute horizon. Conclusions POAF is more closely associated with immediately preceding detectable autonomic destabilization than with preoperative structural substrate. These findings challenge the hypothesis that POAF susceptibility is structurally determined(structural-determinism) and reframe this frequent complication as a dynamic, state-dependent process that may be a target for active prevention.</jats:p>