Assessing heart rate fragmentation to predict atrial fibrillation in the general population aged 65: the PROOF-AF study.

Aims: Screening the general population aged 65 for atrial fibrillation (AF) has been proposed as a preventive measure against potential complications. Metrics derived from heart rate variability (HRV) that depict heart rate fragmentation (HRF) have been suggested to reflect autonomic nervous system dysfunction. The aim of the study was to assess the predictive capacity of HRV markers, including HRF, for AF occurrence over an 18-year follow-up and to develop a predictive score for AF onset among the general population aged 65 at the study's inception. Methods and results: The PROOF prospective cohort consisted of 1011 subjects aged 65 with no history of AF nor history of cardiovascular disease. A 24 h Holter-electrocardiogram was performed at baseline and HRV, from which HRV indices using temporal, frequency, and non-linear methods, and the percentage of inflection points (PIPs) were calculated. The PROOF cohort demonstrated a cumulative incidence of AF of 13.0% during a median follow-up of 17.8 years. Male gender, hypertension, decreased heart rate and α1, and increased premature atrial complex burden, PNN50, and PIP were independent predictors of AF occurrence. Subsequently, the PROOF-AF risk score was developed, ranging from 0 to 7, providing interesting predictive capacity [area under the curve (AUC) = 70.1%, negative predictive value = 92.0%, and accuracy = 72.0%]. The high-risk group (PROOF-AF score from 5 to 7) and the intermediate-risk group (PROOF-AF score from 2 to 4) exhibited a 16.8- and 5.4-fold higher risk, respectively, of developing AF. Conclusion: Heart rate fragmentation parameters, included in the PROOF-AF score, may be used to identify healthy individuals aged 65 who are at high risk of developing AF and assist population screening.