Importance of Testing for Iron Deficiency in Patients with Chronic Heart Failure and Treatment Options

Anemia and Iron Deficiency in Patients with Heart Failure

Chronic heart failure occurs with a prevalence of about 2% and an annual incidence of 0.4% in developed countries. The prevalence of the disease is increasing and is estimated to rise by up to 50% by 2030. Heart failure is associated with poor prognosis, risk of recurrent hospitalization, reduced exercise tolerance, and poor quality of life. It is also characterized by the presence of numerous cardiovascular and non-cardiovascular comorbidities, which further worsen symptoms, quality of life, and prognosis for patients.

Common non-cardiovascular comorbidities include anemia and iron deficiency. Anemia is defined by WHO criteria as a hemoglobin concentration < 120 g/l in women and < 130 g/l in men. Iron deficiency can occur independently of anemia and is defined by a ferritin concentration in the blood < 100 ng/ml or 100–199 ng/ml with reduced transferrin saturation (TSAT) < 20%. It is essential to realize that ferritin is among other things an acute phase protein, and therefore its concentration can be increased in inflammations, cancer, and liver diseases. Iron deficiency occurs in up to 55% of patients with chronic heart failure independently of anemia. In cases of acute heart failure, including acute decompensation of chronic heart failure, it can be present in up to 80% of patients.

Etiology, Diagnosis, and Differential Diagnosis

The cause of iron deficiency is multifactorial: increased losses, reduced intake, absorption disorder, iron metabolism disorder – all these factors can contribute to the development of iron deficiency in heart failure. In the differential diagnosis of iron deficiency, it is always necessary to exclude losses in the gastrointestinal or urogenital tract. Iron deficiency, even without anemia, impairs functional capacity, skeletal muscle function, and contributes to acute circulatory decompensation in patients with chronic heart failure.

Current guidelines of the European Society of Cardiology (ESC) for the diagnosis and treatment of heart failure recommend regular screening for anemia and iron deficiency in all patients with heart failure by examining blood count, ferritin concentration, and transferrin saturation (1).

Therapeutic Options

Correction of anemia using erythropoietin analog darpepoetin did not bring positive results in patients with chronic heart failure: there was no impact on the risk of death and hospitalization for heart failure; on the contrary, the risk of thromboembolic events increased.

Conversely, treatment with intravenous iron carboxymaltose in patients with chronic heart failure with reduced ejection fraction and iron deficiency was associated with symptom improvement, greater exercise tolerance, and better quality of life.

In patients with acute decompensated heart failure, intravenous iron substitution was associated with a reduced risk of first hospitalization for heart failure and death from cardiovascular causes. Oral iron forms are ineffective in this indication and are therefore not recommended for patients with heart failure.

Intravenous iron application in patients with heart failure and iron deficiency is now part of the ESC guidelines for the diagnosis and treatment of heart failure aimed at improving symptoms, exercise tolerance, and quality of life in patients with chronic heart failure and reducing the risk of subsequent hospitalization in patients after acute decompensation of heart failure (1). Intravenous iron is administered repeatedly until complete repletion is achieved, which can be monitored by changes in ferritin concentration.

prof. MUDr. Filip Málek, Ph.D., MBA
Cardiovascular Center, Na Homolce Hospital

References:
1. McDonagh T. A., Metra M., Adamo M. et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021 Sep 21; 42 (36): 3599–3726, doi: 10.1093/eurheartj/ehab368.