Scalable Risk Stratification for Heart Failure Using Artificial Intelligence applied to 12-lead Electrocardiographic Images: A Multinational Study.

Background: Current risk stratification strategies for heart failure (HF) risk require either specific blood-based biomarkers or comprehensive clinical evaluation. In this study, we evaluated the use of artificial intelligence (AI) applied to images of electrocardiograms (ECGs) to predict HF risk. Methods: Across multinational longitudinal cohorts in the integrated Yale New Haven Health System (YNHHS) and in population-based UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we identified individuals without HF at baseline. Incident HF was defined based on the first occurrence of an HF hospitalization. We evaluated an AI-ECG model that defines the cross-sectional probability of left ventricular dysfunction from a single image of a 12-lead ECG and its association with incident HF. We accounted for the competing risk of death using the Fine-Gray subdistribution model and evaluated the discrimination using Harrel's c-statistic. The pooled cohort equations to prevent HF (PCP-HF) were used as a comparator for estimating incident HF risk. Results: Among 231,285 individuals at YNHHS, 4472 had a primary HF hospitalization over 4.5 years (IQR 2.5-6.6) of follow-up. In UKB and ELSA-Brasil, among 42,741 and 13,454 people, 46 and 31 developed HF over a follow-up of 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years, respectively. A positive AI-ECG screen portended a 4-fold higher risk of incident HF among YNHHS patients (age-, sex-adjusted HR [aHR] 3.88 [95% CI, 3.63-4.14]). In UKB and ELSA-Brasil, a positive-screen ECG portended 13- and 24-fold higher hazard of incident HF, respectively (aHR: UKBB, 12.85 [6.87-24.02]; ELSA-Brasil, 23.50 [11.09-49.81]). The association was consistent after accounting for comorbidities and the competing risk of death. Higher model output probabilities were progressively associated with a higher risk for HF. The model's discrimination for incident HF was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. Across cohorts, incorporating model probability with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone. Conclusions: An AI model applied to images of 12-lead ECGs can identify those at elevated risk of HF across multinational cohorts. As a digital biomarker of HF risk that requires just an ECG image, this AI-ECG approach can enable scalable and efficient screening for HF risk.