Abstract 14123: Circulating miRNAs as Biomarkers of Afterload, Acute Vascular Reactivity, and Ventricular-Vascular Coupling in Pediatric Idiopathic Pulmonary Arterial Hypertension: Initial Clinical Studies
Introduction: Although it is known that structural remodeling of the pulmonary arteries (PA) leads to increases in right ventricular (RV) afterload in pediatric idiopathic pulmonary arterial hypertension (iPAH), evaluating such changes early in the process continues to be challenging. Since biological markers such as microRNAs may manifest earlier than functional markers, and since such markers may be detected using simple blood draws, identifying correlations between microRNAs and RV or pulmonary vascular functional parameters would be particularly useful in tracking this disease.
Methods: Blood was collected for 14 pediatric patients with iPAH while undergoing right heart catheterization (RHC). Taqman Low Density Arrays (TLDA) was used to quantify miRNA expression in each patient. RHC data was used to compute pulmonary vascular impedance, ventricular-vascular coupling (VVC), and other hemodynamic markers. VVC was computed from the pressure tracing using the single beat pressure method (Vanderpool RR, et al. Heart 2015;101:37–43).
Results: miR-21, which frequently appears in the PAH literature, was well correlated with pulmonary vascular resistance index (PVRi) (r = 0.81, P < 0.001, see Fig. 1a). Fig. 1b shows that the ratio of miR-150/571 is an excellent predictor of VVC (r = 0.91, P < 0.05). Random Forest statistical machine learning identified miR-683 as a classifier of acute vascular reactivity, confirmed with receiver operating curves (AUC = 0.88, see Fig. 1c)
Conclusion: Over a dozen circulating miRNAs were identified as potential biomarkers for pediatric iPAH from the aforementioned arrays, with several having strong correlations to afterload and acute vascular reactivity. The ratio of miR-150 (recognized as biomarker of PAH) and miR-571 (recognized as biomarker of heart failure) appears particularly promising as a predictor of ventricular-vascular decoupling.
Author Disclosures: V.O. Kheyfets: None. U. Truong: None. J. Dunning: None. K. Hunter: None. C.C. Sucharov: None. D. Ivy: None. S. Miyamoto: None. R. Shandas: None.
- © 2015 by American Heart Association, Inc.