Explainable AI associates ECG aging effects with increased cardiovascular risk in a longitudinal population study.

Aging affects the 12-lead electrocardiogram (ECG) and correlates with cardiovascular disease (CVD). AI-ECG models estimate aging effects as a novel biomarker but have only been evaluated on single ECGs-without utilizing longitudinal data. We validated an AI-ECG model, originally trained on Brazilian data, using a German cohort with over 20 years of follow-up, demonstrating similar performance (r = 0.70) to the original study (0.71). Incorporating longitudinal ECGs revealed a stronger association with cardiovascular risk, increasing the hazard ratio for mortality from 1.43 to 1.65. Moreover, aging effects were associated with higher odds ratios for atrial fibrillation, heart failure, and mortality. Using explainable AI methods revealed that the model aligns with clinical knowledge by focusing on ECG features known to reflect aging. Our study suggests that aging effects in longitudinal ECGs can be applied on population level as a novel biomarker to identify patients at risk early.