Computational modeling of isolated cardiomyocytes, in the context of Heart Failure with reduced ejection fraction

This thesis adopts the BPSLand human ventricular cardiomyocyte model to investigate how heart failure with reduced ejection fraction (HFrEF) remodeling alters coupled electrophysiology, intracellular Ca2+ handling, and contractile function in a controlled in silico setting. Control and HFrEF conditions were simulated under a fixed pacing protocol until steady state, and membrane voltage, Ca2+ transient, L-type Ca2+ current, and active tension signals were analyzed using a consistent biomarker-based workflow. Remodeling effects were quantified through HF/CTRL ratios and relative changes and compared with trends reported by state-of-the-art human ventricular computational studies and, where available, with experimental ranges. The simulations reproduced key HFrEF signatures, including prolonged repolarization and altered Ca2+ cycling, and revealed waveform-level links between plateau dynamics, Ca2+ entry, and downstream Ca2+ handling. Agreement with published reference trends was stronger for electrical and Ca2+-related biomark- ers than for tension kinetics, highlighting the higher sensitivity of mechanical outputs to electromechanical coupling assumptions and biomarker definitions. A robustness assessment confirmed stable biomarker ratios within the tested steady state pacing settings. Overall, the work establishes BPSLand as a platform to quantify cross-domain HFrEF remodeling and provides a baseline for future model refinement and in silico evaluation of candidate therapeutic strategies targeting electrophysiology and Ca2+ handling.