Abstract Body (Do not enter title and authors here): Background: Atrial fibrillation (AF) risk estimation is feasible using clinical factors, inherited predisposition, and artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis. Whether integrating these distinct risk signals improves AF risk estimation is unknown.
Methods: In the UK Biobank prospective cohort study, we estimated AF risk using three models derived from external populations: the well-validated Cohorts for Aging in Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) clinical score, a published AI-enabled ECG-based AF risk model (ECG-AI), and a 1113667-variant AF polygenic risk score (PRS). We estimated discrimination of 5-year incident AF using time-dependent area under the receiver operating characteristic (AUROC) and average precision (AP).
Results: Among 49,293 individuals (mean age 65±8 years, 52% women), 825 (2.4%) developed AF within 5 years. Using single models, discrimination of 5-year incident AF was higher using ECG-AI (AUROC 0.705 [95%CI 0.686-0.724]; AP 0.085 [0.071-0.11]) and CHARGE-AF (AUROC 0.785 [0.769-0.801]; AP 0.053 [0.048-0.061]) versus the PRS (AUROC 0.618, [0.598-0.639]; AP 0.038 [0.028-0.045]). The best performing two component model was CHARGE-AF+ECG-AI (AUROC 0.802 [0.786-0.818]; AP 0.098 [0.081-0.13]), with further improvement observed with inclusion of all components (“Total-AF”, AUROC 0.817 [0.802-0.832]; AP 0.11 [0.091-0.15], p<0.01 vs CHARGE-AF+ECG-AI). Using Total-AF, individuals at high AF risk (i.e., 5-year predicted AF risk >2.5%) had a 5-year cumulative incidence of AF of 5.83% (5.33-6.32). At the same threshold, the 5-year cumulative incidence of AF was progressively higher according to the number of models predicting high risk (zero: 0.67% [0.51-0.84], one: 1.48% [1.28-1.69], two: 4.48% [3.99-4.98]; three: 11.06% [9.48-12.61]. Total-AF achieved favorable net reclassification improvement compared to both CHARGE-AF+ECG-AI (0.039 [0.015-0.066]) and CHARGE-AF+PRS (0.033 [0.0082-0.059]).
Conclusions: Integration of clinical, genetic, and AI-derived risk signals improves discrimination of 5-year AF risk over individual components. Models such as Total-AF have potential to improve the prioritization of individuals for AF screening.