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Functional and Prognostic Implications of Different Iron Deficiency Definitions in Heart Failure: Insights From
Gregory D Lewis1, Anna Giczewska2, Robert J Mentz2
1Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Insights
Iron deficiency (ID) in heart failure (HF) is common. Transferrin saturation (Tsat) and serum iron levels, not just ferritin, better predict functional capacity and outcomes in HF patients.
Area of Science:
- Cardiology
- Hematology
- Nutritional Science
Background:
- Iron deficiency (ID) is prevalent in heart failure (HF) patients.
- Optimal diagnostic criteria and treatment targets for ID in HF remain unclear.
Purpose of the Study:
- To investigate the relationship between various iron indices and definitions of ID with functional capacity, hemoglobin levels, and prognosis in HF.
- To analyze data from the largest study to date on iron repletion in HF.
Main Methods:
- Analysis of data from the HEART-FID trial (N=2,951) involving patients with HF and ID.
- Assessment of ferritin, serum iron, and transferrin saturation (Tsat) levels.
- Multivariable regression to evaluate associations with functional capacity, hemoglobin, and outcomes.
Main Results:
- While most patients met ferritin <100 ng/mL criteria, fewer met iron <13 μM or Tsat <20% criteria.
- Lower Tsat and iron levels were linked to reduced hemoglobin, worse functional class, shorter 6-minute walk distance (6MWD), and poorer outcomes.
- Changes in Tsat and iron over 6 months correlated with changes in hemoglobin and 6MWD.
Conclusions:
- There is significant variability in ID diagnostic criteria fulfillment among HF patients.
- Tsat and serum iron levels, along with their dynamic changes, are more strongly associated with functional capacity, hemoglobin, and prognosis than ferritin levels alone.
- Prioritizing Tsat and iron levels is recommended for defining ID in HF.
Background:
Iron deficiency (ID) is common in patients with heart failure (HF), but optimal use of circulating iron indices as diagnostic criteria and for defining treatment targets remain uncertain.
Objectives:
This study sought how to determine how individual iron studies, and different definitions of iron deficiency, relate to functional capacity, hemoglobin levels, and outcomes in the largest study to date of iron repletion in HF.
Methods:
The HEART-FID (Ferric Carboxymaltose in Heart Failure with Iron Deficiency) trial evaluated ferric carboxymaltose vs placebo in patients with HF with a left ventricular ejection fraction ≤40% and ID defined as ferritin <100 ng/mL or <300 ng/mL with transferrin saturation (Tsat) <20%. We assessed ferritin levels and alternative definitions of ID (serum iron level <13 μM, Tsat <20% in isolation), and continuous measures of iron indices, in relation to functional capacity, hemoglobin levels, and prognosis by multivariable regression.
Results:
By trial design, all patients with complete iron studies at baseline (N = 2,951) had ferritin levels <100 or <300 ng/mL with Tsat <20%. Although 89.8% of participants had ferritin <100 ng/mL, only 59.8% had iron <13 μM, 40.5% had Tsat <20%, and 31.1% had ferritin <30 ng/mL. Tsat <20% and iron <13 μM were associated with lower baseline levels of hemoglobin, worse NYHA functional class, shorter 6-minute walk distance (6MWD), and worse outcomes. In contrast, these measures differed minimally within ferritin strata. Tsat and iron levels remained associated with hemoglobin levels and 6MWD after multivariable adjustment and changes in Tsat and iron levels over 6 months related to changes in hemoglobin level and 6MWD.
Conclusions:
Patients with HF demonstrate wide variability in fulfillment of various diagnostic criteria for ID. Despite ferritin <100 ng/mL being the most common ID criteria met in HEART-FID, Tsat and iron and their changes over time, more than ferritin, were related to functional capacity, hemoglobin levels, and prognosis. Our results support prioritization of Tsat and iron levels in defining iron deficiency in HF (Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency and Sub-Study [HEART-FID]; NCT03037931).
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