Abstract

Abstract Background Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are found in both pre-capillary pulmonary hypertension (PH), including pulmonary arterial hypertension, PH associated with hypoxia/lung disease and chronic thromboembolic pulmonary hypertension, and post-capillary PH associated with left heart disease. We asked the question of whether NT-proBNP concentrations differ among these PH subtypes. Methods Based on right heart catheterization (RHC) data collected at our institution between Jan. 2019 and Dec. 2021, 146 patients were classified as no PH, pre-capillary PH, isolated post-capillary PH (iPC-PH) or combined pre- and post-capillary PH (cPC-PH) according to the 2022 ESC/ERS guidelines (GL). NT-proBNP values were compared across PH groups by Kruskal-Wallis test with Bonferroni correction. The characteristics of subjects with pre-capillary PH and NT-proBNP ≤ or >1.100 pg/mL, a cut-off for severity proposed by the 2022 GL, were compared by chi-square test, T-test, or Mann-Whitney test, as appropriate. We also applied the hemodynamic definitions of the 2018 6th World Symposium on PH (6WSPH) and of the 2015 GL, examined the differences in the distribution of PH groups with the McNemar test, and reassessed NT-proBNP concentrations. Results 44 (30%) of patients did not have PH, 38 (26%) had pre-capillary PH, 18 (12%) had iPC-PH, and 46 (32%) had cPC-PH. NT-proBNP levels were progressively higher from pre-capillary PH to iPC-PH to cPC-PH (Figure). Interestingly, the 25th percentile of the cPC-PH group was 1.138 pg/mL, close to the 1.100 pg/mL cut-off. Compared with patients with pre-capillary PH and NT-proBNP ≤1.100 pg/mL, those with >1.100 pg/mL NT-proBNP had larger right ventricle basal diameter [50 (43-53) vs 43 (36-45) mm; p=0.02], lower TAPSE/sPAP ratio [0.21 (0.15-0.25) vs 0.35 (0.25-0.43), p=0.01], more often massive tricuspid regurgitation (83% vs 20%, p<0.001), higher pulmonary vascular resistance [9.5 (7.6-15.1) vs 5.7 (2.7-7.8) WU; p=0.004], and lower stroke volume index [28 (17-32) vs 36 (32-50) mL/m2; p=0.002]. The proportion of no PH decreased and the one of cPC-PH increased when the 6WSPH or the 2015 GL criteria were used (p for trend <0.001). Nonetheless, the trend of NT-proBNP remained similar to that observed with the 2022 GL definitions (Figure). Conclusions A gradient of NT-proBNP exists across PH groups, with the highest values being in cPC-PH. The concentrations of NT-proBNP in severe pre-capillary PH overlap with those in cPC-PH, indirectly confirming the validity of this biomarker to discriminate the severity of pre-capillary PH.

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