Subclinical atrial fibrillation and the risk of heart failure: insights from ARTESiA

Background Subclinical atrial fibrillation (SCAF) is a common finding in patients with a pacemaker, defibrillator or implantable cardiac monitor. Heart failure (HF) and clinical atrial fibrillation are closely linked, but the relationship between device-detected SCAF and HF is unclear. Purpose We aimed to determine incidence and clinical risk factors for HF events among patients with SCAF. Methods The ARTESiA (Apixaban for the Reduction of Thromboembolism in Patients with Device-Detected Subclinical Atrial Fibrillation) trial investigated the effect of apixaban versus aspirin for stroke prevention in patients with episodes of SCAF ≤24 hours and risk factors for stroke. In this secondary analysis, we explored the association of the number of episodes and duration of SCAF at baseline, SCAF progression, and clinical characteristics with the risk of HF hospitalization and HF-related death. SCAF progression was analysed as a time-dependent covariate and defined as the development of SCAF >24 hours or clinical atrial fibrillation. Risk factors for HF events were assessed using a backward elimination Cox proportional hazards model. Results We included 3,986 patients with complete baseline SCAF data from the ARTESiA trial. Patients had a mean age of 76.8±7.6 years, 1,438 (36%) were women, and 1,132 (28%) had a HF diagnosis at time of study inclusion. Over a mean follow-up of 4.1±1.7 years, SCAF progression was observed in 1,244 patients (31%). HF hospitalization or HF-related death occurred in 515 (13%) patients at a rate of 3.3 (95% CI 3.1-3.6) per 100 person years [PY]. A total of 172 HF-related events occurred after SCAF progression (7.2 events, 95% CI 6.2-8.3, per 100 PY). SCAF progression was an independent risk factor for HF hospitalization or HF-related death (hazard ratio [HR] 2.72, 95% confidence interval [CI] 2.24-3.31). Additional risk factors identified in the multivariable regression analysis were a history of HF (HR 2.30, 95% CI 1.91-2.76), older age (per 5-year increment, HR 1.17, 95% CI 1.10-1.24), moderate-to-severe valve disease (HR 1.86, 95% CI 1.46-2.38), ischemic heart disease (HR 1.50, 95% CI 1.25-1.80), diabetes (HR 1.43, 95% CI 1.19-1.72), peripheral artery disease (HR 1.48, 95% CI 1.14-1.92), and an eGFR <45 (HR 2.56, 95% CI 2.02-3.25) or between 45 and 59 mL/min/1.73m2 (HR 1.47, 95% CI 1.19-1.82). We observed no association between baseline SCAF duration or number of SCAF episodes and HF events. Conclusion HF hospitalization and HF-related death are common in patients with SCAF. Progression to longer SCAF episodes or clinical AF were associated with HF events, but episodes <24 hours were not. These findings underscore the need for close surveillance of SCAF patients to detect complications and potentially improve outcomes.