Fibroblast Growth Factor 23 and Outcomes in Acute Heart Failure

Worsening heart failure (WHF) is a complex clinical syndrome associated with a high risk of mortality and further decompensations, characterized by fluid overload and upregulated inflammatory and fibrotic processes linked to organ dysfunction. Fibroblast growth factor 23 (FGF23) is an emerging proxy of fibrosis and may interact to influence long-term outcomes in WHF patients. This study evaluated the association between FGF23 levels and long-term outcomes in patients with WHF evaluated in the emergency department (ED). A total of 635 patients from the EAHFE registry, enrolled during 2007, 2009, and 2011, were prospectively included. FGF23 was measured in the first blood sample obtained at ED presentation. During a median follow-up of 380 days (interquartile range: 126 to 456), all-cause mortality occurred in 216 patients (34.0%), while 351 patients (55.3%) experienced the composite endpoint of death/WHF ED reconsultation and 295 (46.5%) experienced death/HF hospitalization. Event rates increased progressively across FGF23 levels. Patients with FGF23 above the median (48.4 pg/mL) displayed higher rates (per 100 patient-years) of all-cause mortality (49 vs. 31, p = 0.003), death/WHF ED reconsultation (93 vs. 65, p = 0.003), and death/HF hospitalization (77 vs. 56, p = 0.043). In continuous analyses, each doubling of FGF23 remained significantly associated with an increased risk of all three outcomes after multivariable adjustment. These associations were consistent across clinically relevant subgroups, including those defined by age, sex, and kidney function, supporting the potential prognostic value of FGF23 within this cohort, although external validation is warranted.