MULTIDIMENSIONAL ASSESSMENT AND CHARACTERIZATION OF FRAILTY IN PATIENTS WITH ATRIAL FIBRILLATION: AN ANALYSIS FROM A REAL-WORLD PROSPECTIVE OBSERVATIONAL STUDY

Background. Atrial fibrillation (AF) management should extend beyond stroke prevention and incorporate comorbidity burden, functional status, and frailty assessment. However, the prognostic impact of frailty on clinical outcomes in AF remains incompletely defined. The aim of this study was to evaluate the prevalence and impact of frailty on adverse outcomes in real-world AF patients. Methods. This is a single-center prospective observational study enrolling consecutive patients with ECG documented AF. Patients were stratified into three groups, according to frailty index (FI) based on 30 domains: robust/fit; pre-frail; and frail. The primary endpoint was a composite of all-cause death, acute coronary syndromes, ischemic stroke and/or transient ischemic attack, and heart failure hospitalization. The secondary exploratory endpoints were all-cause death and major bleeding. Linear regression was used to evaluate the association between FI and measures of physical performance. Multivariable Cox proportional hazard models were used to assess the association between frailty and outcomes. Restricted cubic spline (RCS) analysis was performed to characterize the dose-response relationship between FI and the risk of adverse events. Results. Among 1,017 patients (median age 75 [66-81] years; 37.2% females), 105 (10.3%) were classified as robust/fit, 579 (56.9%) as pre-frail, and 333 (32.7%) as frail. Frail patients were older, had a greater comorbidity burden, and received more complex pharmacological regimens compared to robust/fit and pre-frail patients. Linear regression analysis showed that FI was significantly associated with measures of physical performance, particularly the Short Physical Performance Battery score (Beta -0.008; 95% CI -0.010/-0.005; p<0.001) and handgrip strength (Beta -0.001; -0.002/0.000, p=0.001). During a median follow-up of 513 [223-1332] days, 217 (24.7%) events of the primary outcome and 121 (13.8%) deaths were reported. On multivariable Cox analysis, frailty was independently associated with a higher risk of the primary endpoint (aHR 3.18; 95% CI 1.72-5.87) and all-cause death (aHR 3.65; 95% CI 1.43-9.30). RCS curve showed a significant association between FI and the risk of adverse events (p<0.001), with a linear relationship (p for non-linearity = 0.339). No differences were observed concerning the risk of major bleeding. Conclusions. In this prospective cohort of AF patients, pre-frail and frail conditions were highly prevalent. Frailty was associated with more complex pharmacological regimens and with a higher risk of adverse events, supporting the integration of routine frailty assessment into comprehensive AF management.