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Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss‐AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5‐minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal‐to‐normal intervals, square root of the mean squared differences of successive normal‐to‐normal intervals and mean heart rate) were calculated. During follow‐up, an end point committee adjudicated each cause of death. During a mean follow‐up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including β blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1–2.6; P =0.01) and all‐cause death (hazard ratio, 1.42; 95% CI, 1.02–1.98; P =0.04). Conclusions The HRV index measured in a single 5‐minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02105844.

Aims We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. Methods and results We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. Conclusion In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844 Key question The incidence of clinically overt and silent brain infarcts, white matter lesions, and microbleeds, and their impact on cognition in atrial fibrillation (AF) patients are not known. Key finding Over 2 years of follow-up, 5.5% of AF patients developed new brain infarcts, with the majority of them being clinically silent and occurring in anticoagulated patients. New clinically overt and silent brain infarcts were similarly associated with cognitive decline. Take-home message In a contemporary cohort of AF patients, new brain infarcts are frequent despite a high anticoagulation rate. Our data suggest that anticoagulation alone may not be sufficient to prevent brain damage and cognitive decline in all AF patients.