The current ESC guidelines bring into focus the importance of iron status in patients with heart failure. Iron deficiency is associated with decreased physical performance and quality of life regardless of anemia. The European Society of Cardiology therefore recommends compensating for iron deficiency in all heart failure patients by intravenous substitution. Oral iron therapy is usually not sufficient to replenish iron stores.
According to a large European study, one in two patients with chronic heart failure is affected by iron deficiency, with the frequency positively correlated with the severity of heart failure [1]. This has a significant impact on hospitalization and mortality. This is because iron plays a central role in the regulation of cardiac function and peripheral muscles. Iron deficiency generally makes the organism of patients, who are often additionally burdened by high blood pressure, more susceptible to disease. Second, chronically low iron status can exacerbate heart failure. Routine checking of iron metabolism is therefore particularly important in patients with heart failure.
Is there an iron deficiency?
Iron deficiency is defined as a reduction in total body iron. Iron deficiency anemia is only present if the hemoglobin concentration falls below the age- or sex-specific normal value due to iron deficiency. Iron deficiency results from a mismatch between iron intake and iron demand. The cause may be insufficient dietary iron intake on the one hand, or increased iron demand or loss on the other [2]. The most common causes of iron deficiency are increased loss or consumption due to increased menstrual bleeding and malnutrition. Resorption disorders, on the other hand, are rare.
The following three stages of iron deficiency are distinguished [1,6]:
- Non-anemic iron deficiency:
Hb and MCV normal, ferritin decreased; no effect on hematopoiesis. - Non-anemic iron deficiency with microcytosis and/or hypochromia:
Hb normal, ferritin, MCV, and MCH decreased; hematopoiesis and iron-dependent metabolic processes may be impaired. - Iron deficiency anemia:
Hb <12 g/dl (women) or <13 g/dl (men), MCV, MCH and red cell count decreased.
In view of the experience with regard to morbidity and hospitalization, the extent to which therapy for iron deficiency might also affect heart failure was investigated.
Intravenous iron therapy has been shown to be effective
Several years ago, a study showed that i.v. iron substitution resulted in positive effects on performance, complaints and quality of life, with a reduction in hospitalization rates and no serious side effects [3]. Similarly, patients could be classified lower in NYHA. In the meantime, these results have been substantiated in further studies. In a study published in 2020, 1132 patients who required hospitalization for acute heart failure and were diagnosed with iron deficiency received either at least two injections of iron carboxymaltose or placebo [4]. The combined primary end point was hospitalization for heart failure and cardiovascular death. Over the course of 52 weeks, iron therapy reduced this by 21%. The positive results have led the guideline panel to revise the previous recommendation. Since 2016, i.v. administration of iron carboxymaltose should be considered in symptomatic patients (serum ferritin <100 µg/L or ferritin: 100-299 µg/L and transferrin saturation <20%) (Class IIa A recommendation). The 2021 updated ESC guidelines have now differentiated this [5]:
- Iron status should be checked regularly in all patients with heart failure
- In symptomatic heart failure patients (LVEF <45%) with iron deficiency, iron therapy should be considered to relieve heart failure symptoms and improve physical performance and quality of life
- In symptomatic HI patients (LVEF <50%) with iron deficiency who have been recently hospitalized for heart failure, treatment should be considered to reduce the risk of heart failure-related hospitalizations
Because there is limited clinical evidence from randomized clinical trials that have evaluated the use of oral iron in this clientele and these results did not improve exercise capacity or demonstrate adequate replenishment of iron stores, it is recommended that i.v. iron supplementation with ferric carboxymaltose be preferred.
Literature:
- “Heart failure? Get your blood iron levels tested now,” www.herzstiftung.de, (last accessed Sept. 30, 2022).
- Iron Deficiency and Iron Deficiency Anemia, www.onkopedia.com, (last accessed Sept. 30, 2022).
- FAIR-HF Study, www.pressebox.de, (last accessed Sept. 30, 2022).
- “Heart Failure: How Does Iron Therapy Affect Prognosis?”, www.kardiologie.org, (last accessed Sept. 30, 2022).
- McDonagh TA, et al: EHJ 2021; 42(36): 3599-3726.
- Chmiel C, Beise U: Iron deficiency, www.medix.ch/wissen/guidelines, (last accessed Sept. 30, 2022).
HAUSARZT PRAXIS 2022; 17(10): 34
CARDIOVASC 2022; 21(4): 40
