Fibroblast growth factor 23 in children with or without heart failure: a prospective study

BACKGROUND: Elevated fibroblast growth factor 23 (FGF23) levels have been associated with mortality in adults with heart failure (HF), but data on FGF23 levels in paediatric HF are limited. In this prospective cohort study, we aimed to assess the prognostic value of FGF23 in children with chronic HF. METHODS: We prospectively enrolled 40 children with chronic HF and 20 matched healthy controls. In each patient, a complete diagnostic workup was performed, including transthoracic echocardiography to evaluate cardiac systolic and diastolic functions. Serum FGF23, renal function tests, parathyroid hormone, serum calcium and phosphate were measured in patients and controls. N-terminal probrain natriuretic peptide (NT-proBNP) was measured in patients. The severity of symptoms was assessed using the modified Ross HF classification for children. Patients were followed for 1 year, and clinical worsening events such as death and HF hospitalisation were recorded. RESULTS: Patients with HF had significantly higher FGF23 levels compared with controls (355.68±97.27 pg/mL and 60.20±11.04 pg/mL, respectively; p<0.001). Three patients died and 11 were admitted with HF. In comparison with patients without clinical worsening events, these 14 patients exhibited significantly higher FGF23 levels (320.04±89.56 pg/mL and 421.86±75.50 pg/mL, respectively; p<0.001). FGF23 was positively correlated with NT-proBNP and left ventricular end-diastolic diameter and negatively correlated with ejection fraction and fractional shortening. The ability of FGF23 to predict clinical worsening events in patients was analysed using a receiver operating characteristic curve. The optimal cut-off point was 375 pg/mL, with 85.71% sensitivity, 84.62% specificity, positive predictive value of 75.0, negative predictive value of 91.7 and area under the curve (AUC) of 0.878. Multivariable regression analysis revealed that FGF23 is the only independent predictor of clinical worsening events in children with chronic HF. CONCLUSION: FGF23 levels were elevated in children with chronic HF and increased significantly as Ross score class increased. FGF23 levels increased in patients who experienced clinical worsening events.