Rates of Iron Deficiency Differ by Clinical Definition in Heart Failure

A new retrospective analysis identified a higher prevalence of iron deficiency (ID) in patients with acute heart failure (AHF), rather than chronic heart failure (CHF), in a continuous cohort managed at the same institution over the same period.1

This analysis of nearly 1000 patients with HF found notable differences in the detection and classification of ID, when applying several recommended definitions, including those from cardiology, gastroenterology, and general guidelines, affecting the sensitivity and specificity of ID detection.

“ID prevalence greatly varied between the different definitions with potential overestimation of the actual number of patients with true ID who need iron supplementation when applying the cardiology guidelines (low specificity, high sensitivity) and underestimation of patients needing iron therapy when applying the general definition (high specificity, low sensitivity),” wrote the investigative team, led by Guenter Weiss, MD, Department of Internal Medicine II, Medical University of Innsbruck.

Iron is an essential micronutrient for cellular homeostasis and mitochondrial function in the myocardium, and may contribute to HF pathophysiology. Prior evidence has linked the presence of ID to HF severity, worsened exercised capacity and quality of life, and an increased mortality rate, independent of anemia.

Recent evidence-based guidance from the American Gastroenterological Society (AGA) recommended a serum ferritin level <45 ng/mL as the best threshold for diagnosing absolute ID in clinical practice.2 Others from the European Society of Cardiology (ESC) addressed ID with cutoffs as ferritin <100 ng/mL for absolute ID and ferritin 100–299 ng/mL together with transferrin saturation (TSAT) <20% for combined ID.3

A third piece of guidance from the European Crohn's and Colitis Organisation (ECCO) and an international anaesthesiologic consensus statement defined ID as ferritin <30 ng/mL (absolute ID), ferritin 30–100 ng/mL with TSAT <20% for combined ID, or ferritin >100 ng/mL together with TSAT <20% for functional ID.4

For this analysis, Weiss and colleagues sought to address the prevalence of ID in AHF and CHF according to these different definitions, using a continuous monocentric patient cohort. They noted that using these definitions is critical as it can guide the utilization of effective iron replacement therapy.1

The analysis involved 329 patients with AHF and 613 patients with CHF, recruited between February 2011 and May 2022 at the Inssbruck Medical University in Austria. The population was 47% and 32% female, respectively, with a median age of 81 and 64 years. Approximately 30 patients with CHF and 22 patients with AHF received iron supplementation within the preceding 12 months.

Upon analysis, the prevalence of ID was significantly elevated in the AHF cohort, compared with the CHF cohort, according to the general definition (74.8% vs. 32.6%; P <.001), gastroenterology guidelines (75.7% vs. 34.7%; P <.001), and cardiology guidelines (79.9% vs. 47.3%; P <.001). Weiss and colleagues identified notable differences in the prevalence of ID types across the use of the 3 definitions.

Analyses showed that the prevalence of absolute ID was most notable after applying the cardiology definition, compared with the gastroenterology and general definitions (AHF: 44.7% vs. 20.4% vs. 7.0%; CHF: 34.1% vs. 13.4% vs. 7.2%). Further analysis showed that the functional ID prevalence was highest after the application of the general definition, compared with both the gastroenterology and cardiology guidelines (AHF: 34.7% vs. 23.4% vs. 11.6%; CHF, 13.1% vs. 9.0% vs. 3.4%).

Among those classified with absolute or combined ID, according to the cardiology guidelines (n = 494), only 252 received the same classification when applying the general definition. Others were classified as having no (n = 107) and functional (n = 135) ID after the general definition. As a result, Weiss and colleagues indicated the cardiology guidelines could be underestimating the number of patients with functional ID who experience a weakened response to iron supplementation.

“Besides health considerations due to side effects, this depicts a health economic burden due to this huge cohort of HF patients and the need for prospective therapeutic trials to redefine baseline conditions and biomarkers that predict a good response to therapy and a maximum benefit for patients,” they added.

References

1. Lanser L, Pölzl G, Messner M, et al. Prevalence of iron deficiency in acute and chronic heart failure according to different clinical definitions. ESC Heart Fail. Published online February 11, 2025. doi:10.1002/ehf2.15170

2. Ko CW, Siddique SM, Patel A, et al. AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia. Gastroenterology. 2020;159(3):1085-1094. doi:10.1053/j.gastro.2020.06.046

3. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [published correction appears in Eur Heart J. 2021 Dec 21;42(48):4901. doi: 10.1093/eurheartj/ehab670.]. Eur Heart J. 2021;42(36):3599-3726. doi:10.1093/eurheartj/ehab368

4. Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015;9(3):211-222. doi:10.1093/ecco-jcc/jju009