Artificial Intelligence-Derived ECG-Age as a Predictor of Mortality and Cardiovascular Events: A Systematic Review and Meta-Analysis

Abstract

Background

Artificial intelligence (AI)-derived electrocardiographic age (ECG-age) and the difference between ECG-age and chronological age (delta-age) are emerging biomarkers of cardiovascular aging and adverse outcomes, but their prognostic value remains unclear.

Objectives

We performed a systematic review and meta-analysis to evaluate associations between AI-derived ECG-age or delta-age and clinical outcomes.

Methods

Nine databases were searched through May 1, 2025. Eligible studies evaluated mortality or cardiovascular events and reported measures of association. Pooled hazard ratios (pHRs) with 95% confidence intervals (CIs) were calculated via fixed- or random-effects models, with statistical significance set at p < 0.05. The protocol was registered in PROSPERO (CRD420251042467).

Results

Ten studies (2021–2025) with over 550,000 participants from East Asia, the Americas, and the UK were included. Most used convolutional neural networks to estimate ECG-age; delta-age was calculated as ECG-age minus chronological age. Elevated delta-age was associated with increased all-cause mortality (pHR = 1.83, 95% CI: 1.45–2.32) and cardiovascular mortality (pHR = 2.63, 95% CI: 1.93–3.58). Three studies reported increased risk of atrial fibrillation (pHR = 1.96, 95% CI: 1.43–2.69), although data were limited and heterogeneous. Descriptive analyses suggested that greater delta-age predicts incident heart failure and stroke.

Conclusions

AI-derived ECG-age, particularly delta-age, is associated with all-cause and cardiovascular mortality, supporting its role as a noninvasive biomarker of cardiovascular aging. Evidence for atrial fibrillation is suggestive but limited. Standardized algorithms, robust external validation, and prospective multicenter studies are needed to confirm clinical utility and integrate ECG-age into risk stratification, even in asymptomatic individuals.