Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure

Abstract

Background: In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking.

Patients and methods: We conducted a cross-sectional study of 17 healthy children (mean age 13 years) and 20 pediatric patients with heart failure (mean age 12 years) who underwent echocardiography and for whom the following measurements were taken: plasma FGF23 and parathyroid hormone (PTH) and serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association and the Ross classification systems.

Results: Of the 20 patients, 11 had dilated cardiomyopathy, four had congenital heart disease, three had hypertrophic cardiomyopathy, one had a failing heart transplant and one had pulmonary hypertension. Mean phosphate levels in these patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients versus controls (110.9 vs. 66.4 RU/ml; P = 0.03) and higher in patients on diuretics versus other patients (222.4 vs. 82.1 RU/ml; P = 0.01). Levels of FGF23 and NT-proBNP were directly correlated (r = 0.47, P = 0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P = 0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r = 0.63, P = 0.04).

Conclusion: FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation.

Figure 1. Median fibroblast growth factor 23 (FGF23) levels in healthy children and children with heart failure, treated with and without diuretics

Box plots represent median (interquartile range) of FGF23 by group. FGF23 levels were almost double that of in controls (110.9 vs. 66.4 RU/ml; P=0.03), and levels were higher in patients receiving diuretics than in those who were not (222.4 [IQR 133.2 – 587.9] vs. 82.1 [IQR 53.2 – 118.3] RU/ml; P=0.01).

Figure 2. Correlation between NT-proBNP and fibroblast growth factor (FGF23) levels in children with heart failure

FGF23 and NT-proBNP levels were directly correlated in children with heart failure (r=0.47, P=0.04).

Figure 3. Median fibroblast growth factor (FGF23) concentrations in 17 healthy children and 20 children with heart failure, by functional class

Box plots represent median (interquartile range) of FGF23 by NYHA or Ross functional class. Patients with a NYHA or Ross functional class of II or greater had higher FGF23 levels than those with class I (142.5 [IQR 112.5 – 487.4] vs. 92.8 [IQR 54.6 – 122.1] RU/ml; P=0.05).