Transferrin saturation percentage (Tsat) and iron levels, as well as their changes over time, were related to hemoglobin levels, functional capacity and patient outcomes for heart failure (HF), whereas ferritin levels were less so, which may suggest a need to rethink criteria in defining and managing iron deficiency (ID) in this patient population, according to a prespecified secondary analysis of the HEART-FID trial published Oct. 27 in JACC: Heart Failure.

The HEART-FID trial was designed to evaluate the effect of carboxymaltose vs. placebo in 2,951 patients (mean age 69 years; 34% women) with HF and a LVEF ≤40% plus ID, defined as either ferritin <100 ng/mL (comprising 90% of participants) or <300 ng/mL with Tsat <20%.

At enrollment, mean hemoglobin level was 12.6 g/dL, and 47% of patients were in NYHA functional class III-IV. Average six-minute walking distance (6MWD) was 274 m. Among patients, 60% had an iron level <13 µM, 41% had a Tsat <20% and 31% had ferritin <30 ng/mL.

Results showed that a Tsat <20% and iron <13 µM were associated with lower levels of hemoglobin at baseline, as well as worse NYHA functional class, shorter 6MWD and worse outcomes. Of note, within the strata of ferrin, there were minimal differences in these measures.

Additionally, results at six months showed that Tsat and iron levels were associated with hemoglobin levels and 6MWD after multivariable adjustment and that changes in Tsat and iron levels over the time period were related to the changes in the measures.

"Our findings add to a growing body of evidence challenging the appropriateness of reliance on ferritin as a cornerstone of the definition of ID in [heart failure]," write analysis authors Gregory D. Lewis, MD, et al., adding that their research suggests "that Tsat and iron levels should be prioritized as clinically relevant circulating indices of ID."