Reconstructing ventricular activation sequences from epicardial data: Insights from Geodesic Back-Propagation optimization in porcine models.

Cardiac digital twins (CDTs) are emerging as powerful tools in personalized medicine, providing subject-specific models to simulate and understand cardiac function. A central challenge in constructing CDTs is accurately personalizing the structure and function of the His-Purkinje system (HPS), which determines ventricular activation. In this study, we leveraged a novel modified Geodesic-BP method to infer early activation sites (EASs) from epicardial activation times. The EASs can then serve as a surrogate for Purkinje-myocardial junctions, facilitating anterograde ventricular activation. We used both experimental porcine (N = 5) and synthetic (N = 5) datasets of epicardial activation times measured or assigned to locations on an electrode sock. For both datasets, we optimized for initial estimates of 5, 50, 100, and 200 EASs and assessed output variability by repeating the inference process 10 times. Assessments were based on matching the predicted activation times at both the epicardial locations and from intracardiac measurements made with multielectrode needles, and throughout the ventricular myocardium for the synthetic dataset. The algorithm could consistently recover global ventricular activation patterns from epicardial data alone. For the experimental dataset, the minimum and maximum mean absolute differences were 0.19 ms and 3.86 ms on the epicardial sock and 2.65 ms and 10.69 ms for the needles. For the synthetic dataset, the corresponding values were 0.13 ms and 2.81 ms on the sock and 2.42 ms and 14.07 ms ms throughout the ventricular myocardium. However, discrepancies between the epicardial surface and intramural myocardium, overfitting of EASs, and variability across repeated runs revealed key limitations. These findings highlight both the overall potential and current limitations of inferring EASs using the proposed optimization approach. They demonstrate the feasibility of deriving informative activation patterns from limited data, while underscoring the need to incorporate stronger physiological priors and anatomical constraints. Ultimately, our results motivate future efforts to refine simulation-based personalization frameworks, improve robustness, and enhance the physiological realism of CDTs for more accurate and reliable applications.