Interpretable ECG manifolds link longitudinal electrical phenotypes to heart-failure risk in hypertrophic cardiomyopathy

In 650 individuals with hypertrophic cardiomyopathy, a time-dependent lateral/frontal QRS-force coordinate predicts subsequent heart-failure risk, even after censoring septal reduction therapy, atrial fibrillation, and pacing.

• Why it matters: HCM shows heterogeneous electrical patterns, but their continuous structure, within-person evolution, and link to heart-failure risk are not well characterized.
• What they did: The team trained complementary variational-autoencoder models on 5,194 normal-reference ECGs and 2,594 longitudinal visits, then used mixed-effects models to quantify longitudinal drift and time-conditioned within-subject modes.
• The result: HCM overlapped but extended beyond the physiological manifold, and an HCM-oriented manifold reorganized shared electrical modes; genotype related to phenotype position but not trajectory rate.

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