Electrocardiogram-based Deep Learning and Clinical Risk Factors to Predict Atrial Fibrillation.

Artificial intelligence (AI)-enabled analysis of 12-lead electrocardiograms (ECGs) may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful and generalizable improvement in predictive accuracy beyond clinical risk factors for AF. We trained a convolutional neural network ("ECG-AI") to infer 5-year incident AF risk using 12-lead ECGs in patients receiving longitudinal primary care at Massachusetts General Hospital (MGH). We then fit three Cox proportional hazards models, each composed of: a) ECG-AI 5-year AF probability, b) the Cohorts for Heart and Aging in Genomic Epidemiology AF (CHARGE-AF) clinical risk score, and c) terms for both ECG-AI and CHARGE-AF ("CH-AI"). We assessed model performance by calculating discrimination (area under the receiver operating characteristic curve, AUROC) and calibration in an internal test set and two external test sets (Brigham and Women's Hospital and UK Biobank). Models were recalibrated to estimate 2-year AF risk in the UK Biobank given limited available follow-up. We used saliency mapping to identify ECG features most influential on ECG-AI risk predictions and assessed correlation between ECG-AI and CHARGE-AF linear predictors. The training set comprised 45,770 individuals (age 55±17 years, 53% women, 2,171 AF events), and the test sets comprised 83,162 individuals (age 59±13 years, 56% women, 2,424 AF events). AUROC was comparable using CHARGE-AF (MGH 0.802, 95% CI 0.767-0.836; BWH 0.752, 95% CI 0.741-0.763; UK Biobank 0.732, 95% CI 0.704-0.759) and ECG-AI (MGH 0.823, 95% CI 0.790-0.856; BWH 0.747, 95% CI 0.736-0.759; UK Biobank 0.705, 95% CI 0.673-0.737). AUROC was highest using CH-AI: MGH 0.838, 95% CI 0.807-0.869; BWH 0.777, 95% CI 0.766-0.788; UK Biobank 0.746, 95% CI 0.716-0.776). Calibration error was low using ECG-AI (MGH 0.0212; BWH 0.0129; UK Biobank 0.0035) and CH-AI (MGH 0.012; BWH 0.0108; UK Biobank 0.0001). In saliency analyses, the ECG P-wave had the greatest influence on AI model predictions. ECG-AI and CHARGE-AF linear predictors were correlated (Pearson MGH 0.61, BWH 0.66, UK Biobank 0.41). AI-based analysis of 12-lead ECGs has similar predictive utility to a clinical risk factor model for incident AF and both approaches are complementary. ECG-AI may enable efficient quantification of future AF risk.