Validation of a 3D-0D closed-loop model of the heart and circulation -- Modeling the experimental assessment of diastolic and systolic ventricular properties

Computer models of cardiac electro-mechanics (EM) and cardiovascular hemodynamics show promise as an effective means for the quantitative analysis of clinical data and, potentially, provide capabilities to predict the response to therapies. To realize such modeling applications methodological key challenges must be addressed. To endow models with predictive capabilities they must comprehensively encapsulate relevant cardiovascular mechanism, achieve computational efficiency and robustness to enable simulations of prolonged observation periods under a broad range of conditions, and, thus, facilitate model personalization within tractable time frames. Here, these challenges are addressed by introducing a flexible method for coupling a 3D model of bi-ventricular EM to the 0D CircAdapt model representing atrial EM and closed-loop circulation. A detailed mathematical description is given and efficiency, robustness and accuracy of numerical scheme and solver implementation are evaluated. After parameterization and stabilization to a limit cycle under baseline conditions, the model is shown to replicate physiological behaviors by simulating the transient response to alterations in loading conditions and contractility, induced by protocols for assessing of systolic and diastolic ventricular properties.