Anatomical basis of sex differences in the electrocardiogram identified by three-dimensional torso-heart imaging reconstruction pipeline

The electrocardiogram (ECG) is used for diagnosis and risk stratification in myocardial infarction (MI). Women have a higher incidence of missed MI diagnosis and complications following infarction, and to address this we aim to provide quantitative information on sex-differences in ECG and torso-ventricular anatomical features and their interdependence. A novel computational automated pipeline is presented enabling the three-dimensional reconstruction of torso-ventricular anatomies for 425 post-MI subjects and 1051 healthy controls from UK Biobank clinical images. Regression models were created relating torso-ventricular and ECG parameters. We found that female hearts were positioned more posteriorly and superiorly than male, and in MI hearts were oriented more horizontally, especially for women. Post-MI women exhibited less QRS prolongation, requiring 27% more prolongation than men to exceed 120ms. Only half of the sex difference in QRS duration was associated with smaller female cavities. Lower STj amplitude in women was striking, associated with smaller ventricles, but also more superior and posterior cardiac position. Post-MI, T wave amplitude and R axis deviations were more strongly associated with posterior and horizontal cardiac positioning in women than in men. Our study highlights the need to quantify sex differences in anatomical features, their implications in ECG interpretation, and the application of clinical ECG thresholds in post-MI.