Moderate-to-vigorous physical activity and risk of incident atrial fibrillation in atrial cardiomyopathy

Background While moderate-to-vigorous intensity physical activity (MVPA) prevents atrial fibrillation (AF), its efficacy in individuals with established diseased atrial substrates, specifically atrial cardiomyopathy (AtCM), remains unclear. We investigated whether the underlying atrial substrate modifies the association between accelerometer-measured MVPA and incident AF. Methods Among 10,019 UK Biobank participants without major cardiovascular disease, AtCM phenotypes were identified integrating cardiac magnetic resonance and electrocardiography. Adjusted Cox models assessed the association between 7-day accelerometer-measured MVPA and incident AF, incorporating and interaction term for AtCM status. Results AtCM was present in 4.6% of participants. During a median follow-up of 3.2 years, AtCM was associated with a threefold increased risk of AF (hazard ratio [HR] 2.97; 95% confidence interval [CI], 1.69–5.20). AtCM status significantly modified the MVPA-AF association (p for interaction=0.035). Without AtCM, MVPA showed marginal AF risk reduction (HR per 10-minute increase, 0.93; 95% CI, 0.87–1.00). Conversely, with AtCM, higher MVPA strongly lowered AF risk (HR per 10-minute increase, 0.77; 95% CI, 0.64–0.94). The estimated absolute risk reduction was 2.78 events per 1,000 person-years per 10-minute MVPA increase in the AtCM, significantly greater than without AtCM (difference, -2.60; 95% CI, -4.30 to -0.63; p=0.015). These findings remained robust across comprehensive sensitivity analyses, including adjustments for competing risks, predicted clinical risk, and genetic predisposition. Conclusions MVPA significantly reduces AF risk, particularly in individuals with AtCM. Identifying subclinical atrial substrate can guide targeted exercise prescriptions, highlighting MVPA as a potent, non-pharmacological upstream therapy to attenuate progression to clinical arrhythmia.