SPARCL1 and NT-proBNP as biomarkers of right ventricular-to-pulmonary artery uncoupling in pulmonary hypertension

Abstract

Aims: SPARCL1 was recently identified as a biomarker of right ventricular (RV) maladaptation in patients with pulmonary hypertension (PH), and N-terminal pro-brain natriuretic protein (NT-proBNP) is an established biomarker of RV failure in PH. The present study investigated whether NT-proBNP and SPARCL1 concentrations are associated with load-independent parameters of RV function and RV-to-pulmonary artery (RV–PA) coupling as measured using invasive pressure–volume (PV) loops in the RV. Methods: SPARCL1 and NT-proBNP were measured in the plasma of patients with idiopathic pulmonary artery hypertension (IPAH, n = 73). Participants without LV or RV abnormalities served as controls (n = 28). All patients underwent echocardiography and right heart catheterization with invasive PV loop measurements. Results: Our cohort had more females with IPAH than the control group (64% vs. 35%; P = 0.01) and was older [69 (interquartile range, IQR 57–76) vs. 51 (IQR 35–62) years; P < 0.001]. SPARCL1 and NT-proBNP levels were significantly higher in patients with IPAH as compared with controls (P < 0.0001). Patients with IPAH and maladaptive RV remodelling had higher SPARCL1 and NT-proBNP concentrations than those with adaptive RV remodelling (P < 0.01). Both SPARCL1 and NT-proBNP were good predictors of maladaptive RV remodelling in receiver operating characteristic analysis [area under the curve (AUC) (AUCSPARCL1 = 0.75, AUCNT-proBNP = 0.72, P = 0.36 for AUCSPARCL1 vs. AUCNT-proBNP]. The combined predictive value of SPARCL1 and NT-proBNP (AUC 0.78, P < 0.001) for maladaptive RV was numerically higher than that of either SPARCL1 or NT-proBNP alone (P = 0.16 for AUCSPARCL1 + NT-proBNP vs. AUCNT-proBNP and P = 0.18 for AUCSPARCL1 + NT-proBNP vs. AUCSPARC1). SPARCL1 showed numerically a tendency for a better predictive power than NT-proBNP for parameters of early maladaptive RV remodelling such as RV ejection fraction < 50% (AUCSPARCL1 = 0.77, AUCNT-proBNP = 0.67, P = 0.06 for AUCSPARCL1 vs. AUCNT-proBNP), RV end-diastolic diameter > 42 mm (AUCSPARCL1 = 0.72, AUCNT-proBNP = 0.65, P = 0.19 for AUCSPARCL1 vs. AUCNT-proBNP) and RV end-systolic volume index RVESVI > 31 mL/m2 (AUCSPARCL1 = 0.78, AUCNT-proBNP = 0.71, PP = 0.10 for AUCSPARCL1 vs. AUCNT-proBNP). Conclusions: SPARCL1 and NT-proBNP are good predictors of maladaptive RV remodelling and RV–PA uncoupling in IPAH patients. SPARCL1 may be a better predictor of early maladaptive RV remodelling than NT-proBNP.