Ionic modulation of calcium dynamics in simulated human heart failure

Calcium mishandling observed in failing hearts is responsible for contractile dysfunction and arrhythmias. Thereby, calcium dynamics becomes an important target to explore for the restoration of the altered excitation-contraction coupling. In this study, we performed an in-silico sensitivity analysis to understand the mechanisms modulating calcium dynamics in failing human hearts. Using a modified version of the O'Hara et al. human ventricular action potential model, we simulated different failing conditions for every ionic parameter remodeled in heart failure. Calcium biomarkers from simulated endocardial cells, such as systolic and diastolic calcium concentration, were measured and analyzed. The results of this study highlight the importance of maintaining SERCA activity in its normal levels to improve contractility and point to other crucial parameters that also alter calcium handling, such as NCX.