A Feature Selection-Incorporated Simulation Study to Reveal the Effect of Calcium Ions on Cardiac Repolarization Alternans during Myocardial Ischemia

(1) Background: The main factors and their interrelationships contributing to cardiac repolarization alternans (CRA) remain unclear. This study aimed to elucidate the calcium (Ca2+)-related mechanisms underlying myocardial ischemia (MI)-induced CRA. (2) Materials and Methods: CRA was induced using S1 stimuli for pacing in an in silico ventricular model with MI. The standard deviations of nine Ca2+-related subcellular parameters among heartbeats from 100 respective nodes with and without alternans were chosen as features, including the maximum systole and end-diastole and corresponding differences in the Ca2+ concentration in the intracellular region([Ca2+]i) and junctional sarcoplasmic reticulum ([Ca2+]jsr), as well as the maximum opening of the L-type Ca2+ current (ICaL) voltage-dependent activation gate (d-gate), maximum closing of the inactivation gate (ff-gate), and the gated channel opening time (GCOT). Feature selection was applied to determine the importance of these features. (3) Results: The major parameters affecting CRA were the differences in [Ca2+]i at end-diastole, followed by the extent of d-gate activation and GCOT among beats. (4) Conclusions: MI-induced CRA is primarily characterized by functional changes in Ca2+ re-uptake, leading to alternans of [Ca2+]i and subsequent alternans of ICaL-dependent properties. The combination of computational simulation and machine learning shows promise in researching the underlying mechanisms of cardiac electrophysiology.