Pulmonary Vascular Compromise Is Associated With Survival in Pediatric Pulmonary Hypertension: A New Computational...

Pediatric pulmonary arterial hypertension (PAH) has a long asymptomatic period with progressive vascular loss. A recent computational model of simulated PAH in humans has demonstrated that up to 70% of the pulmonary vasculature is lost before clinical PAH criteria are met. We used this model in pediatric subjects with PAH to evaluate whether estimated pulmonary vascular loss or compromise (PVC) was associated with hemodynamic variables, survival, and other clinical outcomes. Retrospective and prospective cohort data were collected for subjects with PAH between 1999 and 2022 treated at our center. Cardiac catheterization and clinical data were compared with PVC estimated by the computational model. Transplant-free survival was associated with lower PVC (72% vs. 88%, p < 0.001) and was also associated with a decrease in PVC over time with no significant change in PVC in subjects who died or underwent transplant. By Kaplan-Meier analysis, 10-year survival was 54% (IQR 35%, 81%) when PVC was more than 80%, compared with 100% survival (IQR 100%, 100%) when PVC was less than 80% (p < 0.001). By Cox proportional hazard regression, PVC was associated with mortality (HR 1.44, p = 0.008). Lower PVC was associated with better clinical outcomes including percent predicted 6-min walk distance, brain natriuretic peptide, and estimated 1-year mortality. These findings demonstrate that PVC is a new computational hemodynamic variable estimating vascular area loss and is associated with transplant-free survival and other clinical outcomes in pediatric PAH. Further, PVC provides an adjunctive tool to potentially capture pulmonary vascular loss early in disease, progression, and response to therapy.