Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies

Abstract

Objectives: In order to describe survival and treatment strategies in pediatric pulmonary arterial hypertension (PAH) in the current era of PAH-targeted drugs and to identify predictors of outcome, we studied uniformly defined contemporary patient cohorts at 3 major referral centers for pediatric PAH (New York [NY], Denver, and the Netherlands [NL]).

Background: In pediatric PAH, discrepancies exist in reported survival rates between North American and European patient cohorts, and robust data for long-term treatment effects are lacking.

Methods: According to uniform inclusion criteria, 275 recently diagnosed consecutive pediatric PAH patients who visited the 3 referral centers between 2000 and 2010 were included.

Results: Unadjusted survival rates differed between the center cohorts (1-, 3-, and 5-year transplantation-free survival rates: 100%, 96%, and 90% for NY; 95%, 87%, and 78% for Denver; and 84%, 71%, and 62% for NL, respectively; p < 0.001). Based on World Health Organization (WHO) functional class and hemodynamic parameters, disease severity at diagnosis differed between the center cohorts. Adjustment for diagnosis, WHO functional class, indexed pulmonary vascular resistance, and pulmonary-to-systemic arterial pressure ratio resolved the observed survival differences. Treatment with PAH-targeted dual and triple therapy during the study period was associated with better survival than treatment with PAH-targeted monotherapy.

Conclusions: Survival rates of pediatric PAH patients differed between 3 major referral centers. This could be explained by differences between the center cohorts in patients' diagnoses and measures of disease severity, which were identified as important predictors of outcome. In this study, treatment with PAH-targeted combination therapy during the study period was independently associated with improved survival.

Keywords: pediatrics; pulmonary hypertension; survival.