Pulmonary Hypertension in Rural Minnesota

Abstract

We aimed to measure and validate differences in plasma concentrations of proteins that are associated with prognosis in children with idiopathic PAH and due to CHD to improve risk stratification. Background: Pulmonary arterial hypertension (PAH) in children is a complex and heterogenous condition, mostly complicating congenital heart disease (CHD) and carrying an increased risk of mortality. Clinical management is difficult due to the scarcity of data to have an accurate assessment of risk in this subgroup of patients. Methods: In this observational cohort study, we enrolled 29 children (mean age: years 13.8 §10.7, median: 10) with PAH, idiopathic and due to CHD. Blood samples were collected at routine clinical appointment visits. In the same day, all data for clinical status, biochemical and no-invasive tests were collected. Clinical data within 1 year of follow up have been recorded. We used an aptamer-based assay of 1000 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against multiparametric clinical assessment or natriuretic peptides. The primary endpoint was a combination of life threatening arrhythmias, rehospitalization and death. Results: 3 proteins differentiated worse prognosis in 29 consecutive patients with PAH with 1 year of follow-up. 3 proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to inflammatory cascade and myocardial stress and coagulation. Conclusion: A combination of three circulating proteins identifies patients with PAH with a high risk of arrhythmia and hospitalization, independent of existing clinical assessments, and might have a use to stratify the risk in children.