Soluble transferrin receptor and hepcidin but not standard iron biomarkers are reliable prognostic biomarkers in heart failure

Background Definition or iron deficiency (ID) in heart failure (HF) is currently based on serum ferritin and the transferrin saturation (TSAT). In recent years, controverse discussions have emerged about using ferritin, as it is an acute-phase protein that does not always reflect true iron stores. The aim of this analysis was to evaluate the accuracy of standard and alternative iron biomarkers in predicting disease outcome. Methods We analyzed 238 AHF and 547 CHF patients treated at our University Hospital 11/2020–05/2022 with available iron status at baseline without iron supplementation within the last year, after out-patient visit or hospitalization. Patients were followed until 10/2023. We performed sex-stratified Cox regression analysis adjusted for age, NT-proBNP, LV-EF, CRP and hemoglobin to evaluate the predictive value of iron biomarkers on outcome (all-cause mortality, HF decompensation and combined endpoint of both). Results Serum ferritin did not predict outcome in AHF and CHF, while a lower ferritin/CRP ratio predicts all-cause mortality and combined endpoint in AHF and CHF. Low TSAT was related to risk of HF decompensation and combined endpoint in CHF but not AHF. High soluble transferrin receptor (sTfR) levels were predicting outcome in CHF and trend to predict all-cause mortality in AHF. Low hepcidin levels were also predicting outcome in CHF, while Cox regression analysis suggested that hepcidin does not predict outcome in AHF. Univariate analysis of hepcidin subgroups showed that both low (≤8.6μg/L) and high (>20μg/L) hepcidin levels were related to an elevated all-cause mortality in AHF. When correcting for CRP only hepcidin levels ≤8.6μg/L remained predictive for all-cause mortality in AHF. Conclusions We could show that serum ferritin levels fail to identify AHF and CHF patients with risk for an adverse outcome thus questioning the suitability of the current ferritin-based ID definition. Introduction of the ferritin/CRP ratio and the alternative iron biomarkers hepcidin and sTfR might help to better identify iron imbalances and patients with poor prognosis in both AHF and CHF.