1Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; 2Justus-Liebig-Universität Giessen Kardiologie und Angiologie Gießen, Deutschland; 3Kerckhoff Klinik GmbH Kardiologie / Experimentelle Kardiologie Bad Nauheim, Deutschland; 4CCB am AGAPLESION BETHANIEN KRANKENHAUS Kardiologie Frankfurt am Main, Deutschland; 5Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik II - Pneumologie Gießen, Deutschland; 6Kerckhoff Klinik GmbH Allgemeine Pneumologie Bad Nauheim, Deutschland
Background:
The relationship between RV contractility and RV afterload is referred to as RV-to- pulmonary artery (RV-PA) coupling and it is an important prognostic determinant in patients with pulmonary arterial hypertension (PAH). RV maladaptation is characterized by progressively decreasing RV-PA coupling, which eventually results in RV-PA uncoupling. Invasive pressure-volume (PV) measurement in the RV is the current gold standard for the load-independent assessment of systolic and diastolic RV function and RV-PA coupling.
Echocardiographic evaluation of the RV is essential during the diagnostic work-up of patients with PAH. Several echocardiographic parameters such as TAPSE/PASP, RV free wall (RVFW) strain/PASP, RVEF, and RVESVI have been identified as important non-invasive surrogates of RV maladaptation and RV-PA coupling.
NT-proBNP is an established biomarker of RV failure in PAH, and SPARCL1 was recently identified as a biomarker of RV maladaptation in patients with PH. However, it remains unclear whether NT-proBNP and SPARCL1 concentrations are associated with PV loop parameters of RV function and RV-PA coupling.
Objective: The main aim of this study is to compare the predictive value of echocardiographic parameters, biomarkers, and the combination of these two diagnostic features for the prediction of RV maladaptation in patients with PAH.
Methods: SPARCL1 and NT-proBNP were measured by enzyme-linked immunosorbent assay in blood samples of patients with idiopathic PAH (IPAH, n=73). All patients underwent an echocardiographic assessment, including RV strain and 3D-echocardiography, right heart catheterization, and invasive PV loop measurements using conductance catheters. RV maladaptation was defined as Ees/Ea <1.0 or Ees/Ea 1.0 – 1.2 and central venous pressure (CVP) ≥8.
Results: In IPAH patients, SPARCL1 and NT-proBNP correlated well with Ees/Ea (r=0.51 for SPARCL1 and r=0.49 for NT-proBNP). However, TAPSE/PASP, RVFW strain/PASP, and 3D-RVEF correlated better with Ees/Ea (r=0.54 for TAPSE/PASP, r=0.53 for RVFW strain/PASP and r=0.56 for 3D-RVEF) than did the two biomarkers. RVFW strain/PASP correlated better with PV loop parameters of load-independent RV contractility (r=0.49 for Ees) and diastolic function (r=0.62 for Eed and r=0.46 for Tau) than SPARCL1, NT-proBNP, TAPSE/PASP, and 3D-RVEF.
Receiver operating curve analyses showed that TAPSE/PASP (AUC=0.82) and RVFW strain/PASP (AUC 0.82) had a significantly better predictive value for RV maladaptation than NT-proBNP (AUC=0.71, p≤0.05 for all comparisons). SPARCL1 showed a tendency towards better predictive value than NT-proBNP in terms of RV maladaptation (AUC=0.73), RVESVI >31 ml/m² (AUCSPARCL1=0.78, AUCNT-proBNP=0.71) and RVEF <50% (AUCSPARCL1=0.77, AUCNT-proBNP=0.67). The combined predictive value of TAPSE/PASP, SPARCL1, and NT-proBNP (AUC=0.86) was higher than the separate values of all other echocardiographic parameters or biomarkers, but the difference was not significant.
In a binary logistic regression SPARCL1, TAPSE/PASP, and RVFW strain/PASP were independent predictors of RV maladaptation.
Conclusion: SPARCL1 shows a tendency for better prediction of early maladaptive changes than NT-proBNP. The echocardiographic parameters TAPSE/PASP and RVFW strain/PASP are better predictors than NT-pro-BNP of RV maladaptation in patients with PAH. A combination of echocardiographic parameters and biomarkers may improve the detection of RV maladaptation in PAH.