Abstract
Subject-specific modeling is a powerful tool in cardiovascular research, providing insights beyond the reach of current clinical diagnostics. Limitations in available clinical data require the incorporation of uncertainty into models to improve guidance for personalized treatments. However, for clinical relevance, such modeling must be computationally efficient. In this study, we used a one-dimensional (1D) fluid dynamics model informed by experimental data from a dog model of chronic thromboembolic pulmonary hypertension (CTEPH), incorporating measurements from multiple subjects under both baseline and CTEPH conditions. Surgical intervention can alleviate CTEPH, yet patients with microvascular disease (e.g., remodeling and narrowing of small vessels) often exhibit persistent pulmonary hypertension, highlighting the importance of assessing microvascular disease severity. Thus, each lung was modeled separately to account for the heterogeneous nature of CTEPH, allowing us to explore lung-specific microvascular narrowing and resistance. We compared inferred parameters between baseline and CTEPH and examined their correlation with clinical markers of disease severity. To accelerate model calibration, we employed Gaussian process (GP) emulators, enabling the estimation of microvascular parameters and their uncertainties within a clinically feasible timeframe. Our results demonstrated that CTEPH leads to heterogeneous microvascular adaptation, reflected in distinct parameter shifts. Notably, the changes in model parameters strongly correlated with disease severity, especially in the lung previously reported to have more advanced disease. This framework provides a rapid, uncertainty-aware method for evaluating microvascular dysfunction in CTEPH and may support more targeted treatment strategies within a timeframe suitable for clinical application.