Functional and Prognostic Implications of Different Iron Deficiency Definitions in Heart Failure: Insights From...

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.

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.

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.

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.

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).