Criteria for Iron Deficiency in Congestive Heart Failure
Iron deficiency in CHF is defined as serum ferritin <100 μg/L (absolute iron deficiency) or serum ferritin 100-299 μg/L with transferrin saturation (TSAT) <20% (functional iron deficiency). 1, 2
Diagnostic Criteria
Primary Definition (European Society of Cardiology)
- Absolute iron deficiency: Serum ferritin <100 μg/L
- Functional iron deficiency: Serum ferritin 100-299 μg/L with TSAT <20%
Laboratory Assessment
- Measure both serum ferritin and transferrin saturation simultaneously in all patients with CHF 2
- TSAT calculation: (serum iron concentration/total iron-binding capacity) × 100 1
Emerging Evidence on Diagnostic Criteria
Recent research suggests that TSAT may be a more reliable indicator of iron deficiency than ferritin:
- TSAT ≤19.8% showed superior sensitivity (94%) and specificity (84%) compared to the traditional definition when validated against bone marrow iron staining 3
- Serum iron ≤13 μmol/L also demonstrated excellent performance (sensitivity 94%, specificity 88%) 3
- Low TSAT, but not ferritin, was independently associated with adverse outcomes in patients with decompensated heart failure 4
Screening Recommendations
- Screen all newly diagnosed heart failure patients for iron deficiency 2
- Re-evaluate iron status 1-2 times per year and after hospitalization for heart failure 2
- Consider additional testing when standard markers are inconclusive:
- Reticulocyte hemoglobin concentration (CHr)
- Soluble transferrin receptor (sTfR) 1
Clinical Significance
- Iron deficiency is common in CHF (40-70% of patients) and clinically significant regardless of anemia status 2
- Iron deficiency is associated with:
Additional Evaluation
When iron deficiency is identified, consider:
- Evaluating for gastrointestinal pathology, including malignancy (potential source of blood loss)
- Assessing renal function (serum creatinine and GFR)
- Testing thyroid function 1
Pitfalls and Caveats
- Ferritin is an acute phase reactant and may be elevated in inflammatory conditions despite iron deficiency
- Serum ferritin levels between 20-100 μg/L are actually within normal range for healthy adults, questioning the validity of using <100 μg/L as a cutoff 5
- Some patients with TSAT <20% but ferritin >300 μg/L may still have functional iron deficiency but are excluded by current criteria 5, 6
- Medications like neprilysin inhibitors and SGLT2 inhibitors may affect ferritin levels by mobilizing endogenous iron stores 7
Recent evidence suggests that the current ferritin-driven definition may need reconsideration, with some experts proposing that hypoferremia (TSAT <20%, with ferritin <400 μg/L) may be a more appropriate definition for iron deficiency in heart failure patients 5, 7.
Despite these emerging perspectives, the current European Society of Cardiology guidelines and clinical trial protocols continue to use the established definition of ferritin <100 μg/L or ferritin 100-299 μg/L with TSAT <20% for diagnosing iron deficiency in CHF patients.