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Criteria for Iron Deficiency in Patients With Heart Failure
Gabriele Masini1, Fraser J Graham2, Pierpaolo Pellicori2
1Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
Insights
Different iron deficiency definitions impact heart failure prognosis. Lower transferrin saturation (TSAT) and serum iron levels, but not guideline criteria, predict higher mortality in heart failure patients.
Area of Science:
- Cardiology
- Hematology
Background:
- Heart failure (HF) guidelines define iron deficiency (ID) using serum ferritin or transferrin saturation (TSAT).
- Inflammation in HF can complicate the interpretation of serum ferritin levels.
- The study addresses the impact of varying ID definitions on prevalence and prognosis in HF patients.
Purpose of the Study:
- To investigate how different definitions of iron deficiency (ID) affect its prevalence.
- To examine the relationship between various ID definitions and prognosis in ambulatory patients with chronic heart failure (HF).
Main Methods:
- Evaluated prevalence, patient characteristics, and outcomes associated with different ID definitions.
- Data collected from 4,422 HF patients at a regional clinic between 2001 and 2019.
- Analyzed outcomes based on TSAT <20%, serum iron ≤13 μmol/L, serum ferritin <100 ng/mL, and guideline criteria for ID.
Main Results:
- 68% of HF patients met guideline criteria for ID, with 35% having TSAT >20%.
- ID was more prevalent in women and those with more severe symptoms, anemia, or preserved ejection fraction.
- TSAT <20% and serum iron ≤13 μmol/L were linked to higher 5-year mortality, unlike guideline criteria or low ferritin.
Conclusions:
- Discrepant results arise from different ID definitions regarding prevalence and prognosis.
- Definitions lacking specificity may obscure benefits of iron therapy; those lacking sensitivity may exclude eligible patients.
- Further research via subgroup analyses in randomized trials is recommended to clarify optimal ID definitions.
Background:
Guidelines on heart failure (HF) define iron deficiency (ID) as a serum ferritin <100 ng/mL or, when 100-299 ng/mL, a transferrin saturation (TSAT) <20%. Inflammation (common in HF) may hinder interpretation of serum ferritin.
Objectives:
This study sought to investigate how different definitions of ID affect its prevalence and relationship to prognosis in ambulatory patients with chronic HF.
Methods:
Prevalence, relationship with patients' characteristics, and outcomes of various ID definitions were evaluated among patients with HF referred to a regional clinic (Hull LifeLab) from 2001 to 2019.
Results:
Of 4,422 patients with HF (median age 75 years [range: 68-82 years], 60% men, 32% with reduced left ventricular ejection fraction), 46% had TSAT <20%, 48% had serum iron ≤13 μmol/L, 57% had serum ferritin <100 ng/mL, and 68% fulfilled current guideline criteria for ID, of whom 35% had a TSAT >20%. Irrespective of definition, ID was more common in women and those with more severe symptoms, anemia, or preserved ejection fraction. TSAT <20% and serum iron ≤13 μmol/L, but not guideline criteria, were associated with higher 5-year mortality (HR: 1.27; 95% CI: 1.14-1.43; P < 0.001; and HR: 1.37; 95% CI: 1.22-1.54; P < 0.001, respectively). Serum ferritin <100 ng/mL tended to be associated with lower mortality (HR: 0.91; 95% CI: 0.81-1.01; P = 0.09).
Conclusions:
Different definitions of ID provide discordant results for prevalence and prognosis. Definitions lacking specificity may attenuate the benefits of intravenous iron observed in trials while definitions lacking sensitivity may exclude patients who should receive intravenous iron. Prespecified subgroup analyses of ongoing randomized trials should address this issue.
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