Impact of anxiety and depression in patients with atrial fibrillation: insights from two international registries

Background Limited data exist on the impact of anxiety and depression on clinical outcomes in patients with atrial fibrillation (AF). Purpose To compare clinical characteristics and outcomes between AF patients with and without anxiety and/or depression. Methods Post-hoc analysis of two prospective registries (EORP-AF and APHRS-AF). Patients were classified as asymptomatic or symptomatic for anxiety/depression based on self-reported questionnaires. Logistic regression identified factors associated with symptomatic status. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of adverse outcomes. Multivariable models were adjusted for: age≥75, sex, enrolment setting, education level, symptomatic AF, obesity, heart failure, coronary artery disease, peripheral vascular disease, chronic kidney disease, dementia, and use of oral anticoagulants. The primary outcome was a composite of all-cause death and major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death, MACE, major bleeding, and exploratory analyses of each MACE component, including thromboembolic events, cardiovascular death, acute coronary syndromes. Sensitivity analyses assessed outcomes by anxiety/depression severity, and subgroup analyses evaluated consistency across clinical subgroups. Results Of 12,614 patients, 4,825 (38.3%) were symptomatic (mean age 69±12 years; 48% female) for anxiety/depression. Symptomatic patients were more often female, European, obese, and had a higher prevalence of symptomatic AF and heart failure. After a median follow-up of 569 days, symptomatic patients for anxiety/depression showed a higher incidence of the composite outcome (annual incidence rates: 9.3% vs. 6.9% per year, P<0.001), all-cause death (5.8 vs. 4.3, P<0.001), MACE (6.1 vs. 4.0, P<0.001), cardiovascular death (2.4 vs. 1.3, P<0.001), acute coronary syndromes (2.5 vs. 1.8, P=0.005), thromboembolic events (1.6 vs. 1.1, P=0.003) (Table). On multivariable Cox regression analysis, symptomatic patients showed a higher risk of the composite outcome (HR 1.26, 95% CI 1.10–1.45), all-cause death (HR 1.31, 95% CI 1.12–1.55), MACE (HR 1.44, 95% CI 1.19–1.74), cardiovascular death (HR 1.87, 95% CI 1.41–2.47) (Table). A graded relationship was observed between anxiety/depression severity and risk, with asymptomatic patients showing the lowest risk of the composite outcome, followed by mild, and the highest risk among moderate-to-severe cases (Figure). These associations were consistent across subgroups. Conclusion In patients with AF, self-reported symptoms of anxiety and/or depression were associated with a higher risk of adverse outcomes, particularly among those with moderate-to-severe symptoms. These findings highlight the need for greater awareness of psychological assessment in AF management.