Simulation of Cardiac Contractility Modulation with Single Cell Action Potential Human Models

Cardiac contractility modulation (CCM) therapy represents a significant advancement in the treatment of heart failure, a condition that remains a leading cause of morbidity and mortality worldwide. This therapy involves the delivery of precisely timed electrical signals to the myocardium during the absolute refractory period. Computer modelling has become a powerful tool in the study of cardiac electrophysiology as it allows for detailed simulation of heart electrical activity. For this reason, we test the response to a CCM-like stimulation of two single-cell action potential models: the new model of human ventricular cardiomyocytes electromechanics, BPSLand, and the novel electromechanical hiPSC-CM model, hiPSC-CM-CE. For the first CCM beat in both models, there was an increase in contraction amplitude, stable during CCM. Upon removal of CCM, the amplitude decreased, consistent with the experimental findings. Additionally, only the BPSLand model showed an increased [Ca2+]i amplitude on the first CCM beat relative to before CCM. These results demonstrate that CCM stimulation modifies intracellular calcium handling properties also in silico. With this work, we aimed to support the investigation of this new intra-cardiac therapy at the single-cell level using computational models.