Abstract Introduction Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood. Purpose We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF. Methods We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction. Results We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p<0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p<0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p<0.001, Table). Conclusion In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure