Relationship of Iron Deficiency, Anemia and Combination of Iron Deficiency With Anemia With Severity of Manifestations of Chronic Heart Failure. Additional Analysis of the Study “Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)”
Authors: Mareev V. Yu. , Kobalava Zh. D. , Mareev Yu. V. , Begrambekova Yu. L. , Karapetyan L. V. , Galochkin S. A. , Kazakhmedov E. R. , Lapshin A. A. , Garganeeva A. A. , Kuzheleva E. A. , Efremushkina A. A. , Kiseleva E. V. , Barbarash O. L. , Pecherina T. B. , Galyavich A. S. , Galeeva Z. M. , Baleeva L. V. , Koziolova N. A. , Veklich A. S. , Duplyakov D. V. , Maksimova M. N. , Yakushin S. S. , Smirnova E. A. , Sedykh E. V. , Shaposhnik I. I. , Makarova N. A. , Zemlyanukhina A. A. , Skibitskiy V. V. , Fendrikova A. V. , Skibitskiy A. V. , Spiropulos N. A. , Seredenina E. M. , Orlova Ya. A. , Eruslanova K. A. , Kotovskaya Yu. V. , Тkacheva O. N. , Fedin M. A. 
Published: December 2024

Aim      To evaluate the role of iron deficiency (ID) identified by various criteria, anemia, and the combination of ID and anemia in determining the severity of the clinical course of chronic heart failure (CHF) in a retrospective analysis of data from 498 patients who participated in the ID-CHF-RF Russian multicenter program.

Material and methods  ID was diagnosed by the following three criteria established by the European Society of Cardiology (ESC) and the Russian Society of Cardiology (RSC): 1) ferritin concentration <100 μg/l or ferritin concentration 100-299 μg/l in combination with a decreased transferrin saturation (TS) <20%; 2) ID criteria that showed a high sensitivity and specificity when compared with bone marrow morphology (BMM): TS ≤19.8% or serum iron (SI) ≤13 μmol/l; and 3) a composite index including a ferritin concentration <100 μg/l in combination with TS <20% and SI ≤13 μmol/l. The presence of anemia was defined as a hemoglobin concentration of less than 12.0 g/dl in women and less than 13.0 g/dl in men according to the criteria of the World Health Organization.

Results Concomitant anemia was detected in 40.3% of patients with CHF; in 85.1% of cases, anemia was combined with the SI concentration below normal. CHF patients with concomitant anemia were significantly older and had low levels of not only red blood cells and hemoglobin but also all parameters of iron metabolism, i.e., SI, ferritin concentration, and TS. The mean deviation of the red blood cell size, that characterizes the degree of anisocytosis, was significantly increased in patients with anemia, especially with a low SI. These patients had a higher CHF functional class, elevated levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) and walked a shorter distance in the 6-minute walk test, which reflects significantly more severe manifestations of CHF with concomitant anemia, particularly in combination with a low SI. The incidence of ID was 83.1% (including 23.3% in combination with anemia) according to the ESC/RSC criteria; 74.5% (including 43.3% with anemia) according to the BMM criteria; and 51.6% (including 51.7% with anemia) according to the composite index, which seems to be stricter compared to the first two criteria. Regardless of the assessment method (by total weighted average data), in ID combined with anemia, not only the hemoglobin concentration was significantly reduced but all three analyzed parameters of iron metabolism were also significantly reduced (SI 9.0 μmol/l vs. 10.4 μmol/l; ferritin 41 μg/l vs. 59 μg/l; TS 8.5% vs. 12.9%) compared to ID without anemia, respectively. The CHF severity and the NT-proBNP concentration were also maximum for the combination of ID and anemia, in contrast to ID without anemia, regardless of the ID criterion used. A more accurate comparison of the methods for determining ID in CHF in the context of their prognostic value will be obtained by analyzing the data of a two-year follow-up of patients in this study, which will be the subject of the next article.

Conclusion      This analysis suggests that the presence of concomitant ID without anemia or anemia without ID moderately affects the severity of clinical manifestations of CHF and may be rather markers than factors determining the course of the disease, and in this case, does not require special correction with iron medications. And only ID anemia (a combination of ID with anemia) in patients with CHF can be considered a condition requiring special correction (for example, with intravenous medication) in addition to optimal therapy for CHF. This conclusion does not change depending on the used criteria for ID and requires verification in new RCTs.