Investigating the Mechanistic Effects of Medication on Pulmonary Hypertension

Pulmonary Hypertension (PH) affects the right heart, and is characterized by high mean pulmonary arterial pressure (mPAP).Treprostinil is a drug for PH that dilates downstream blood vessels, reducing pressure, peripheral vascular resistance (PVR), and right ventricle (RV) workload.Combining clinical data and model-derived metrics, this work aims to better understand the impact of Treprostinil in the interplay between RV, proximal, and peripheral arteries.Data from two PH patients undergoing treatment, a responder and a non-responder, were compared.Metrics of RV function, proximal pulmonary artery (PA), RV-PA coupling, and PVR, were analyzed.Compared to the responder, the non-responder had worsened RV function (15% increase vs 20% decrease in end-systolic volume), impaired coupling (0.36 vs 0.60), and increased mPAP (89 vs 46mmHg) despite decreased PVR (38 vs 13 WU), significant dilation of proximal PA (15-45% vs 1-6%) with minimal angulation changes, and increased arterial stiffness (pulse wave velocity: 8 vs 4.2 m/s ).Findings suggest that Treprostinil is more effective in earlier stages of PH and that the large PA dilation in the non-responder might be a compensatory mechanism for insufficient downstream vasodilation.The study highlights the potential of computational models to provide markers to assess treatment responses and disease progression in PH, however further research with larger patient groups is needed.