Osteopontin predicts adverse right ventricular remodelling and dysfunction in pulmonary hypertension

Abstract

Background: Osteopontin (OPN) was found upregulated in several heart failure models and appears to play an important role in myocardial remodelling. As we have previously demonstrated that OPN predicts mortality in patients with pulmonary hypertension (PH), we now evaluated whether OPN also predicts adverse right ventricular (RV) remodelling and dysfunction in PH.

Methods: We prospectively included 71 patients with PH of different etiology in this study. OPN plasma level were determined by ELISA and assessed for correlation with RV dilatation and dysfunction determined by echocardiography.

Results: OPN plasma values significantly correlated with RV end-diastolic diameter, Tricuspid Annular Plane Systolic Excursion (TAPSE) and Tricuspid Annular Systolic Velocity (TASV) (r = 0·43, P = 0·0002; r = -0·46, P = 0·0006; r = -0·31, P = 0·02). Furthermore, stratification of our study population according to RV end-diastolic diameter and RV dysfunction revealed that patients with enlarged and functionally impaired RV's display higher OPN levels (956 ng/mL vs. 628 ng/mL, P = 0·0005; 1108 ng/mL vs. 792 ng/mL; P = 0·02). Next, we determined OPN cut-off values for the detection of RV remodelling and dysfunction by receiver operating curve analyses and further stratified these parameters in a multivariate analysis. Here, OPN emerged as an independent predictor of RV dilatation and dysfunction. Finally, we demonstrate synergism of OPN and NT-proBNP in the prediction of RV dilatation and dysfunction by calculation of the Rothman Synergy Index.

Conclusion: In summary, OPN predicts adverse RV remodelling and dysfunction in PH. Together with our previously published data regarding OPN's value for the prognostication of death in PH, we believe that OPN can improve risk stratification in patients with PH beyond current assessment standards.