Background: Pulmonary hypertension (PH) is a life-threatening condition with a 5-year mortality of 65-75% in children. While therapy is directed toward lowering pulmonary vascular resistance, the most important predictor of mortality is the ability of the right ventricle (RV) to adapt to elevated pulmonary pressures. NT-proBNP, an established marker of left ventricular dysfunction correlates with functional status in children with PH, but has limited sensitivity (57%) for predicting death or need for transplantation. Therefore, there is a critical need for RV-specific biomarkers to assess the mechanism of RV adaptation and progression to RV failure in PH. We have shown that plasma microRNA-21 (miR-21), a pro-fibrotic and cell death marker, increases with increasing tissue fibrosis in children with Tetralogy of Fallot. We hypothesize that plasma miR-21 expression will increase with disease severity in children with PH with congenital heart disease (CHD). Methods: We conducted a cross sectional study of children with PH with collection of blood samples from June 2014 to October 2017. miR-21 expression was assessed in the plasma using qRT-PCR and correlated with demographic and clinical data at the time of blood collection. Plasma miR-21 expression is presented as fold-change and baseline clinical data as median and range. Results: Matched patient data and blood samples were available on 35 patients with PH. We evaluated children with PH with associated CHD (N=21) including atrioventricular septal defects, left to right shunts, anomalous pulmonary venous return, and conoventricular defects. Table 1 shows clinical data based on Panama functional status. miR-21 expression did not correlate with duration of PH. miR-21 expression increased with worsening functional status: 1 vs. 1.86 vs. 2.1-fold (p<0.05). miR-21 expression decreased by 1.7-fold in patients on systemic pulmonary vasodilatory therapy (N=7) vs. patients on oral therapy (N=8). miR-21 expression correlated positively with NT-proBNP (r=0.64) and pulmonary capillary wedge pressure (=0.55) and negatively with cardiac index (r=0.89) (p<0.05). Conclusion: Plasma miR-21 expression increases with worsening functional status and may suggest increasing RV myocardial fibrosis and cell death. Lower miR-21 levels in patients on systemic vasodilatory therapy may indicate a subgroup of patients within a functional class who have undergone favorable remodeling. Plasma miR-21 expression may add prognostic value to current biomarkers in children with PH and associated CHD. [ABSTRACT FROM AUTHOR]