Ionic remodelling following myocardial infarction explains phenotypic variability in ECG and arrhythmic substrate but not in ejection fraction

Aims Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic remodelling, which are reflected as variable phenotypes. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with the post-MI electrophysiological heterogeneities are unknown. We aim to unravel how phenotypic ECG and EF variability in post-MI may be explained by the impact of ionic remodelling on spatio-temporal dispersion of repolarization using human biventricular electromechanical modelling and simulation. Methods and Results Multiple post-MI ECG phenotypes observed clinically were investigated using multi-scale modelling and simulation, calibrated and evaluated using experimental and clinical data. Acute stage T-wave inversion was caused by delayed repolarization in the epicardial border zone (BZ), and Brugada phenocopy was generated by repolarization delay and activation failure in the BZ. Upright tall T-waves in chronic MI represented large repolarisation dispersion between BZ and surrounding tissue, which promoted ectopic propagation at fast pacing. T-wave morphology alternans were present at fast-pacing due to prolonged refractoriness in the mid-myocardium. Post-MI ionic remodelling reduced EF through inhibition of calcium transient amplitude, but the EF at resting heart rate was not sensitive to the extent of repolarisation heterogeneity and the risk of repolarisation abnormalities at fast pacing. Conclusions In acute post-MI, ionic remodelling and its effect on refractoriness and propagation failure in the BZ have a strong impact on phenotypic ECG variability, whereas in chronic post-MI, the repolarisation dispersion across the BZ is crucial. T-wave and QT abnormalities are better indicators of repolarisation heterogeneities than EF in post-MI. ### Competing Interest Statement The authors have declared no competing interest.