Prevalence of iron deficiency in acute and chronic heart failure according to different clinical definitions

Iron is essential to maintain cellular energy metabolism in the myocardium. Impaired cellular iron availability negatively affects myocardial physiology and can aggravate heart failure (HF). Iron deficiency (ID) is frequently found in patients with acute and chronic HF (AHF, CHF) and associated with clinical outcome. The aim of this analysis was to assess the true ID prevalence in HF patients on the basis of different ID definitions.

We performed a retrospective analysis of 329 AHF and 613 CHF patients, recruited between 02/2021 and 05/2022 at the Innsbruck Medical University (47%/32% female, median age 81/64 years). ID was defined according to a general definition, gastroenterology and cardiology guidelines as ferritin <30 or <45 ng/mL or <100/ng/mL (absolute ID), ferritin 30-100 or 45-150 or 100-299 ng/mL plus TSAT <20% (combined ID), and ferritin >100 or >150 or ≥300 ng/mL plus TSAT <20% (functional ID).

ID prevalence was significantly higher in AHF compared with CHF patients: general definition (74.8% vs. 32.6%, P < 0.001), gastroenterology guidelines (75.7% vs. 34.7%, P < 0.001), cardiology guidelines (79.9% vs. 47.3%, P < 0.001). We found distinctive differences in prevalence of ID types between the three definitions. Absolute ID prevalence was highest when applying cardiology compared with gastroenterology guidelines and general definition (AHF: 44.7% vs. 20.4% vs. 7.0%; CHF: 34.1% vs. 13.4% vs. 7.2%), while frequency of combined ID was almost equally distributed. Functional ID prevalence was highest when applying general definition compared with gastroenterology and cardiology guidelines (AHF: 34.7% vs. 23.4% vs. 11.6%; CHF: 13.1% vs. 9.0% vs. 3.4%). Out of 494 patients classified as having absolute or combined ID according to the cardiology guidelines, only 252 patients received the same classification while 107 and 135 patients were classified having no and functional ID when applying the general definition.

We show that ID prevalence is higher in AHF versus CHF patients in a continuous cohort of HF patients managed at the same institution over the same period of time. There were distinctive differences in detection of ID and the type of ID when applying several recommended definitions thus affecting sensitivity and specificity for absolute and functional ID detection. This may result in exclusion of patients, which may benefit from iron supplementation and inclusion of those who may not respond or even anticipate site effects. Our study calls for the urgent need of prospective trials for redefinition of ID and identification of biomarkers associated with therapeutic response to optimize patient outcomes.