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 sought to evaluate this model in pediatric subjects with PAH and evaluate whether estimated pulmonary vascular compromise (PVC) can predict survival and other clinical outcomes.

Retrospective and prospective cohort data were collected for all 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). Freedom from transplant/death 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 1.1, p=0.008). Lower PVC was associated with better percent predicted 6-minute walk distance (-0.25, 95% CI [-0.35, -0.14], p<0.001), lower log brain natriuretic peptide (0.12, 95% CI [0.07, 0.18], p<0.001), and lower estimated 1-year mortality (0.01, 95% CI [0.01, 0.02], p<0.001).

Estimated PVC predicts transplant-free survival and other clinical outcomes in pediatric PAH and provides an adjunctive tool to potentially capture pulmonary vascular loss early in disease.