Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH).n = 627), dilated cardiomyopathy , or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36).In this observational study, FGF-23 was measured in the plasma of patients with PH (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile . Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m2. Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis.Median FGF-23 plasma levels were higher in PH patients than in healthy controls (FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH.The online version contains supplementary material available at 10.1007/s00392-023-02162-y. Pulmonary hypertension (PH) increases the afterload of the right ventricle (RV). Chronic pressure overload leads to RV remodeling and may result in right heart failure, which is associated with adverse outcomes . MaladapFibroblast growth factor 23 (FGF-23) is a bone-derived protein that acts as a regulator in phosphate and vitamin D homeostasis and is elevated in patients with chronic kidney disease (CKD) . A direcTo date, there is a paucity of data on the role of FGF-23 in RV remodeling. A recent study reported an association between high serum levels of FGF-23 and pulmonary arterial hypertension (PAH) in a small cohort of patients undergoing dialysis . InteresThe aim of the present study was to examine the utility of FGF-23 as a biomarker of RV dysfunction in a large cohort of PH patients. Furthermore, FGF-23 plasma levels were compared in patients with PH, dilated cardiomyopathy (DCM), left ventricular hypertrophy (LVH) in severe aortic stenosis, and controls without any LV or RV abnormalities.n = 542 patients with chronic thromboembolic pulmonary hypertension (CTEPH), n = 85 with idiopathic pulmonary hypertension (IPAH), n = 35 patients with LVH and severe aortic stenosis, and n = 59 DCM patients were enrolled in this observational cohort study. Individuals (n = 34) without any RV or LV abnormalities served as controls. Study inclusion took place at the Kerckhoff Heart and Thorax Center and at the University Hospital of Giessen and Marburg (UKGM) Campus Gießen, Department of Cardiology.Between December 2013 and January 2021, Data on demographics, comorbidities, and symptoms were collected for all patients. RV and LV function were evaluated by transthoracic echocardiography, and patients with pulmonary hypertension were also examined by right heart catheterization .All patients gave written informed consent before enrollment in this study. The Institutional Review Board of the University of Giessen approved the study .Patients with IPAH and CTEPH were included if they fulfilled all of the following criteria: age > 18 years, mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, left ventricular ejection fraction (LVEF) ≥ 50%, and no LVH (end-diastolic interventricular septum thickness (IVSd) ≤ 13 mm).2) and preserved LV function (LVEF > 55%), IVSd > 12 mm.Patients with LVH and pressure overload were included in the study according to the following criteria: chronic LV pressure overload due to severe aortic stenosis , LVEDd > 56 mm as measured by echocardiography, at the time of diagnosis.2. eGFR was estimated using the CKD-EPI method.Samples from a cohort without any RV or LV abnormalities were used as controls. Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 mVenous blood samples were obtained by venipuncture at inclusion and collected in plain tubes. Plasma aliquots were processed immediately and stored at − 80 °C until further analysis. Biomarker measurements were performed by experienced staff who were blinded to patients’ characteristics.C-terminal FGF-23 was measured by a second-generation human FGF-23 enzyme-linked immunosorbent assay (ELISA) kit (MicroVue Human FGF-23 (C-Term) EIA-96 Test, Quidel Corporation, Athens, Ohio, USA) with a minimum detectable concentration of 1.5 RU/mL. The intra-assay coefficients of variation are 2.4% and 1.4% at 33.7 and 302 RU/mL, and the respective interassay coefficients of variation are 4.7% and 2.4% at 33.6 and 293 RU/mL.n = 335) NT-pro-BNP levels were measured in serum with an electrochemiluminescence immunosassay using monoclonal antibodies . The intra-assay coefficients of variation are 1.5% and 1.3% at 124 and 14.142 pg/mL, respectively, and the respective interassay coefficients of variation are 2.7% and 1.7% at 125 and 32,930 pg/mL as declared by the package insert. The lower detection limit for the NT-proBNP assay is 5 pg/mL.In a subset of patients  curve analysis was performed to assess the predictive value of FGF-23 regarding RV maladaptation, defined as TAPSE < 17 mm and cardiac index (CI) < 2.5 L/min/m2. Binary logistic regression analysis was performed to identify whether FGF-23 is a glomerular filtration rate (GFR)-independent predictor of parameters of RV function. A two-tailed p value < 0.05 was considered to define statistical significance. Statistical analysis was performed using IBM SPSS Statistics Version 28.0 .Continuous variables are shown as mean ± standard deviation or as median with interquartile range, as appropriate. Categorial variables are displayed as numbers and percentages. The Shapiro–Wilk test was applied to assess parametric distribution. Independent cohorts were compared using Student’s p < 0.05 for all comparisons). PH patients had higher PASP measured by echocardiography than that of all other groups. In addition, the echocardiographic RV parameters TAPSE and TAPSE/PASP were lower in PH patients than in the other groups, whereas RVEDD was higher .Clinical characteristics of patients with PH, LVH, DCM, and controls are shown in Table Clinical characteristics of patients with PH, LVH, DCM, and controls are shown in Table p < 0.01 for all comparisons), whereas there were no significant differences between PH, DCM, and LVH patients  and eGFR . No significant correlation was observed between FGF-23 levels and echocardiographic parameters of LV or RV function.  but did correlate with eGFR , RVEDD , TAPSE , TAPSE/PASP , mPAP , and LVEF . No correlation was observed between FGF-23 and right atrial pressure , cardiac index , LVEDd  IVSd  or LVPWd  in DCM patients .An analysis of clinical and imaging parameters across FGF-23 tertiles in patients with PH is shown in Table p < 0.05 for all comparisons) or the low tertile . The CI was higher in the low-FGF-23 tertile than in the middle (p < 0.05) or high tertile . Additionally, correlation analysis in the subgroup of PH patients with CKD (n = 93) confirmed the findings from the entire PH cohort (Suppl. Table 2).eGFR was lower in the high-FGF-23 tertile compared with the middle and low tertiles  plasma levels of FGF-23 are higher in patients with PH, LVH, and DCM than in healthy controls, whereas no significant differences were found between patients with PH, LVH, and DCM; (2) increased FGF-23 plasma levels are associated with systolic RV dysfunction, RV dilation, lower CI, and higher pulmonary pressure and vascular resistance in PH patients; (3) FGF-23 is an eGFR-independent predictor of RV maladaptation.The continuous pressure overload caused by PH induces remodeling processes in the RV. In early-stage PH, the RV adapts to its higher afterload by a four to fivefold increase in contractility to maintain cardiac output. This increase is achieved by hypertrophy and changes in cardiomyocyte contractile properties that enable ventriculoarterial coupling to be maintained .Chronic progressive pressure overload, however, leads to increased wall stress, capillary rarefication, and neurohumoral activation and other pathological stimuli that induce maladaptive remodeling in the RV. These changes lead to RV dilation, fibrosis, and systolic and diastolic dysfunction . As a reThe early detection of maladaptive changes could be essential for the improvement of therapeutic strategies in patients with pulmonary hypertension. Currently, the gold-standard method for evaluating right ventricular–pulmonary artery (RV–PA) coupling is the measurement of the pressure–volume (PV) loop-derived end-systolic RV elastance/pulmonary elastance (Ees/Ea) ratio , 37. HowFGF-23, which is mainly secreted by osteocytes, plays an important role in phosphate and vitamin D homeostasis . In earlOur findings that FGF-23 plasma levels were increased in patients with LVH and DCM compared with healthy controls are consistent with previous studies , 21, 30.n = 48) FGF-23 levels were correlated to mPAP, CI, PVR, NT-proBNP und REVEAL Risiko-Score [Whereas there are numerous studies examining the association of FGF-23 expression and parameters of LV remodeling, there is a paucity of evidence on the association between FGF-23 and RV remodeling. In a small cohort of PAH patients Supplementary file2 (DOCX 14 kb)Below is the link to the electronic supplementary material.