Validation of a Computational Model for Simulating Hemodynamic Effects of Premature Ventricular Complexes

Premature ventricular complexes (PVCs) can lead to adverse cardiac outcomes through complex pathophysiological mechanisms, particularly in how cellular-level effects manifest as whole-heart dysfunction. To enable realistic beat-to-beat simulation of cardiovascular physiology during PVCs, we enhanced the multiscale CircAdapt model by implementing a validated force-interval relationship (FIR) in its sarcomere module. This implementation was essential to capture the intricate relationship between PVC coupling intervals and subsequent changes in myocardial contractility. We calibrated the enhanced model using canine experimental data and validated it against human in-vivo hemodynamic measurements, employing both single-chamber Langendorff and closed-loop circulatory configurations. The model successfully reproduced PVC-induced hemodynamic patterns, including characteristic pressure changes during extra-systoles and post-extra-systoles, with corresponding alterations in stroke volume. The incorporation of the FIR proved crucial for capturing beat-to-beat variations in cardiac function. These results imply that calcium-mediated sarcomere mechanics play a key role in generating PVC-induced hemodynamic responses, highlighting CircAdapt's potential for understanding the multi-scale consequences of PVCs and their pathophysiology.