Background 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.

Methods and Results 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).

Conclusions 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.

What Is New?

A new computational model can estimate pulmonary vascular area loss or pulmonary vascular compromise (PVC).

PVC can detect early vascular loss and is associated with transplant-free survival and clinical outcomes in pediatric pulmonary arterial hypertension.

What Are the Clinical Implications?

The authors have declared no competing interest.

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The project was supported by a Children's Hospital of Philadelphia Pediatric Academic Development Fund and Parker B. Francis Foundation. In addition, it was funded by K08HL140129 (DBF) and K23HL150337 (CMA).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Institutional Review Board of The Children's Hospital of Philadelphia.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All data will be publicly available from the corresponding author upon publication. The code for building the computational model can be found at https://github.com/AdamMajer/bshouty-lung-model.

https://github.com/AdamMajer/bshouty-lung-model