Interpretable ECG heart age and serial electrical aging in 399,786 electrocardiograms

BACKGROUND: Interpretable ECG Heart Age models estimate the Heart Age Gap, the difference between ECG-predicted and chronological age. Whether a single measurement of accumulated burden predicts the future pace of electrical aging is unknown. OBJECTIVES: To derive and internally validate an interpretable ECG Heart Age from routine 12‑lead measurements, quantify within-person aging using a measurement-based Electrical Aging Score (mEAS), and test whether baseline Heart Age Gap predicts subsequent mEAS progression. METHODS: We analyzed 399,786 standard 12‑lead ECGs from 128,605 patients recorded from April 2015 to June 2025. ECG Heart Age was calculated from six routine ECG measurements and sex, compared with a sex-specific expected value from strict-normal ECGs, and internally validated in a 20% held-out sample. Annualized mEAS slopes in 7885 patients with at least three ECGs spanning more than 5 years were modeled using piecewise mixed-effects regression. RESULTS: In held-out strict-normal ECGs (n = 15,701 from 10,439 patients), ECG Heart Age matched chronological age (median gap -0.19 years), whereas abnormal ECGs appeared older (median gap +6.58 years; area under the curve 0.79). All aging markers increased over time (all p < 0.001), and mEAS progression accelerated 3.3-fold after age 65. Baseline Heart Age Gap did not predict subsequent mEAS slope (r = -0.08). In a 3-year landmark analysis, higher early mEAS slope was associated with later left bundle branch block and paced rhythm but not atrial fibrillation or flutter. CONCLUSIONS: ECG Heart Age reflects accumulated electrical burden, whereas serial mEAS reflects ongoing pace. Baseline burden did not predict subsequent pace, so a single ECG does not convey both; whether the two index distinct biological processes remains untested. External validation against clinical outcomes is required before clinical use.