Effect of Abnormal Calcium Dynamics on Heart Failure based on a Biophysical Modeling Study

Heart failure (HF) is a global health challenge, contributing to significant morbidity and mortality. It is classified into two types: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), both of which involve abnormalities in calcium handling and ion channel remodeling, leading to electrical and mechanical dysfunction. Despite advancements in HF management, the complex relationship between cellular-level alterations and organ-level dysfunction remains poorly understood. Computational modeling provides a powerful tool for exploring these mechanisms, allowing for integration of processes across biological scales. This study builds on existing models by incorporating the effects of calcium dynamics, which are often overlooked in current simulations. Our findings demonstrate that HF-induced changes in calcium dynamics currents significantly prolong action potential duration and increase heterogeneity across ventricular cell types by more than 20%, contributing to arrhythmia risk. Simulations using a biventricle model showed that incorporating calcium dynamics resulted in prolonged QT intervals in both HFrEF and HFpEF conditions.Clinical Relevance- These results underscore the critical role of calcium dynamics in HF and suggest potential therapeutic strategies to address electrophysiological disturbances and mitigate arrhythmia risk.