Integration of Left Atrial Function Assessment, Genetic Risk, and Clinical Risk Factors Improves Prediction of Incident Atrial Fibrillation

Abstract

Background Integration of imaging, genetic, and clinical markers might improve risk assessment of atrial fibrillation (AF). We explored whether the addition of left atrial (LA) function and polygenic risk score (PRS) to a clinical risk score improves risk prediction of AF.Methods A total of 36 919 individuals without AF who were assessed for LA emptying fraction (evaluated by cardiac magnetic resonance imaging) and PRS were analyzed from the UK Biobank imaging enhancement.Results Over a median of 2.9 (2.0-4.2) years, 535 individuals developed incident AF. Per-SD decrease in LA emptying fraction and increase in PRS was associated with a hazard ratio of 2.13 (95% CI, 1.99-2.27) and 1.65 (95% CI, 1.52-1.79) for incident AF, respectively. C-index increase when LA emptying fraction was added to CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation) was 0.036 (95% CI, 0.013-0.057) and when joint LA emptying fraction and PRS was added to CHARGE-AF was 0.057 (95% CI, 0.034-0.081). At a 3-year risk threshold of 3%, the predicted net benefit was 2.48 per 1000 people for a model including LA emptying fraction, PRS, and CHARGE-AF compared with 0.30 per 1000 people for a model including CHARGE-AF only. In addition, a 6.5-fold risk gradient was observed for AF-mediated stroke or other systemic embolism after accounting for LA emptying fraction and PRS.Conclusions Integration of LA emptying fraction and PRS significantly improved risk prediction of incident AF when added to CHARGE-AF.