Background:

Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular (LV) remodeling and recent clinical studies identified FGF-23 as an independent predictor of mortality in patients with LV failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study assesses the of FGF-23 as a biomarker of maladaptive RV function in patients with pulmonary hypertension (PH). Furthermore, it aims to compare FGF-23 levels in patients with LV and RV remodeling in order to detect potential differential expression of FGF-23 in RV and LV under pathological conditions.

Methods:

In this observational study FGF-23 was measured by enzyme-linked immunosorbent assay in the plasma of patients with PH (n=627), dilated cardiomyopathy (DCM, n=59), or LV hypertrophy (LVH) with severe aortic stenosis (n=35). Participants without LV or RV abnormalities served as controls (n=36). RV function was assessed using transthoracic echocardiography and right heart catheterization.

Results:

Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p<0.001). There were no significant differences between PH, DCM, and LVH patients.

Tertile analysis of FGF-23 levels (I [Low]: < 78 RU/mL; II [middle]: 78-117 RU/mL; III: [high] > 117 RU/mL, Fig.1) in PH patients revealed an association between high FGF-23 levels and higher levels of NT-proBNP (p<0.001) as well as lower estimated glomerular filtration rate (eGFR, p<0.001). Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) and right atrial pressure (RAP) and a lower cardiac index (CI) than patients in the middle (p<0.05 for all comparisons) and low (p<0.001 for all comparisons) tertiles. Additionally, high FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP.

FGF-23 was as good predictor of RV dysfunction, defined as TAPSE <17 mm and CI <2.5 L/min/m² in receiver operating characteristic (ROC) analysis (AUC_FGF-23 = 0.72). The results of binary regression analysis indicated that FGF-23 is an eGFR-independent predictor of TAPSE <17 mm, CI <2.0 l/min/m², RVEDD >43 mm, and RAP >7 mmHg (Table 1).

Conclusion:

Our analysis showed that increased FGF-23 plasma levels are associated with systolic RV dysfunction, RV dilation, and higher pulmonary pressures in PH patients. Furthermore, FGF-23 was a good predictor of RV maladaptation and may thus serve as a biomarker for maladaptive RV remodeling in patients with PH. However, there were no significant differences in FGF-23 levels between patients with PH, LVH and DCM.

Table 1:

Fig.1: