Refining iron deficiency definitions in acute hospitalised heart failure
H Oh, J Hyun, S LeeAbstract
Background
Recent randomised trials evaluating the efficacy of intravenous iron replacement in heart failure (HF) patients with iron deficiency (ID) have not demonstrated clear improvements in major clinical outcomes, although symptomatic benefits have been consistently observed. Several studies suggest that transferrin saturation (TSAT), rather than serum ferritin, more closely reflect prognosis and may help identify patients who are more likely to respond to iron replacement. However, most of these studies were conducted in stable, ambulatory chronic HF populations, and it remains uncertain whether the same criteria are applicable to hospitalised patients with acute HF.
Methods
Of the 7,351 hospitalised HF patients enrolled in the Korean Heart Failure III prospective registry, 1,294 with available serum iron markers were included in the analysis. ID was defined using both standard (serum ferritin <100 ng/mL or 100 to 299 ng/mL with TSAT <20%) and new criteria; criterion 1: serum iron <6.5 μmol/L or TSAT <10%; criterion 2: serum iron <6.5 μmol/L or TSAT <15%.
Results
Standard ID criteria did not differentiate clinical outcomes including all-cause mortality (ACM) and cardiovascular mortality (CVM). Functional ID, rather than absolute ID, was associated with higher risk of CVM in multivariate regression analysis (p = 0.019). Serum iron and TSAT values were inversely related with CVM, while serum ferritin values demonstrated positive correlation. In the multivariate regression analyses, new ID criteria were significantly associated with higher risk of CVM (criteria 1: hazard ratio 3.26, 95% confidence interval 1.49–7.16, p = 0.003; criteria 2: HR 2.64, 95% CI 1.14–6.10, p = 0.023).
Conclusions
In hospitalised acute HF, current ID definition failed to capture its prognostic significance, largely due to reliance on ferritin levels. Our findings suggest that serum iron and TSAT, rather than ferritin, provide more appropriate criteria for defining ID and predicting clinical outcomes. Revised criteria emphasising lower TSAT and incorporating serum iron levels for hospitalised HF patients may be considered to better identify subset at increased risk of adverse outcomes and to guide future therapeutic strategies.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.