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

Oliver Dörr; Stanislav Keranov; Paulina van Wickern; Holger Nef; Christian Hamm; Pascal Bauer; Christian Troidl; Samuel Sossalla; Sandra Voss; Christoph Liebetrau; Manuel J Richter; Henning Gall; Werner Seeger; Ardeschir Ghofrani; Athiththan Yogeswaran; Khodr Tello

doi:10.1002/ehf2.15159

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

ESC Heart Fail. 2024 Dec 9. doi: 10.1002/ehf2.15159. Online ahead of print.

Authors

Oliver Dörr^{1

2

3}, Stanislav Keranov¹, Paulina van Wickern¹, Holger Nef⁴, Christian Hamm^{1

3}, Pascal Bauer¹, Christian Troidl^{1

3}, Samuel Sossalla^{1

3

5}, Sandra Voss^{3

5}, Christoph Liebetrau^{2

3}, Manuel J Richter⁶, Henning Gall⁶, Werner Seeger⁶, Ardeschir Ghofrani⁶, Athiththan Yogeswaran⁶, Khodr Tello⁶

Affiliations

¹ Department of Cardiology and Angiology, University of Giessen, Giessen, Germany.
² Cardioangiological Center Bethanien (CCB), Frankfurt, Germany.
³ German Center for Cardiovascular Research (DZHK) Partner Site Rhine-Main, Bad Nauheim, Germany.
⁴ Department of Cardiology, Heart and Vascular Center Bad Segeberg, Bad Segeberg, Germany.
⁵ Department of Cardiology, Kerckhoff Heart and Lung Center, Bad Nauheim, Germany.
⁶ Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Giessen, Germany.

PMID: 39654310
DOI: 10.1002/ehf2.15159

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) (AUC_SPARCL1 = 0.75, AUC_NT-proBNP = 0.72, P = 0.36 for AUC_SPARCL1 vs. AUC_NT-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 AUC_{SPARCL1 + NT-proBNP} vs. AUC_NT-proBNP and P = 0.18 for AUC_{SPARCL1 + NT-proBNP} vs. AUC_SPARC1). 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% (AUC_SPARCL1 = 0.77, AUC_NT-proBNP = 0.67, P = 0.06 for AUC_SPARCL1 vs. AUC_NT-proBNP), RV end-diastolic diameter > 42 mm (AUC_SPARCL1 = 0.72, AUC_NT-proBNP = 0.65, P = 0.19 for AUC_SPARCL1 vs. AUC_NT-proBNP) and RV end-systolic volume index RVESVI > 31 mL/m² (AUC_SPARCL1 = 0.78, AUC_NT-proBNP = 0.71, PP = 0.10 for AUC_SPARCL1 vs. AUC_NT-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.

Keywords: Ees/Ea; PV loops; RV dysfunction; RV remodelling; RV–PA coupling.