Cardiac 3D electromechanical tissue simulations for cardiac safety analysis

Cardiac safety is a critical aspect of drug development. Computational modeling has emerged as a valuable tool to accelerate drug development and regulatory decision-making. However, accurately capturing the complex interactions within the heart requires detailed models. Computational tools often focus on cardiac electrophysiology, lacking the contribution of active contraction. We aimed to enhance the predictability and application of cardiac 3D models by investigating the effects of electromechanical coupling on cardiac simulations. We developed a fully coupled electromechanics model by integrating the ToR-ORd electrophysiological model and the Land model of active contraction. A population of models was built, starting with 1000 myocytes generated through random scaling of 29 parameters of the baseline model. Model refinement led to a population of 190 models that accurately matched …