Iron deficiency

Iron is a very important molecule for the correct functioning and energy production in muscle cells. It is also important for oxygen transport via hemoglobin in the red blood cells.
Patients with heart failure can develop iron deficiency due to many factors:
- Intestinal malabsorption (due to gastrointestinal congestion in right heart failure, use of proton pump inhibitors,...).
- Gastrointestinal blood loss (antiaggregants, anticoagulants or intestinal pathology). Screening for intestinal blood loss should be performed according to clinical assessment and/or current guidelines.
- Low-grade systemic inflammation and suppression of erythropoiesis (functional iron deficiency).
- Malnutrition due to decreased appetite and iron intake.

Iron deficiency is therefore frequent and occurs in approximately 50% of patients with heart failure. It is an indicator of a worse prognosis and is associated with lower exercise capacity. These effects are independent of the degree of anemia. Even without anemia, iron deficiency causes a lower exercise capacity and a worse prognosis.

The diagnosis of iron deficiency in a heart failure patient

Note :

A low serum iron alone is insufficient for the diagnosis of iron deficiency, which requires a documented decrease in ferritin and/or transferrin saturation.
Ferritin is falsely elevated in inflammation. It is an acute phase protein. Correct assessment of iron status is therefore not possible during episodes of inflammation or infection.

Heart failure causes gastrointestinal malabsorption of iron. This makes peroral substitution not useful. Taking peroral iron supplements has been tested in a large clinical heart failure study, but could not demonstrate any added value. Intravenous administration of iron is efficient. In addition, peroral supplements cause side effects (black stools, constipation, stomach upset, etc.).
Supplementation with intravenous administration of iron improves the quality of life, exercise capacity and reduces symptoms and short-term hospitalizations due to heart failure in HFrEF patients, regardless of the degree of anemia. However, positive effects on mortality and hospitalizations have not yet been demonstrated in the longer term and are being further investigated.

In HFmrEF and HFpEF, there is no proven benefit and no reimbursement for intravenous correction of iron deficiency but it may be considered in certain cases.

Maximum dose per administration is 1000 mg IV. Sometimes the total dose must be divided into 2 administrations, with a minimum of 1 week between 2 administrations.
Rapid administration is possible over 30 minutes.
Little risk of allergic reactions.
Possible side effect: transient hypophosphatemia (lasting several weeks, especially after > 1 administration). If more pronounced, it can cause symptoms of fatigue, muscle cramps, constipation, nausea, bone pain and osteomalacia.

Dosage schedule:

Advantage: the entire required intravenous dose can be administered in one time.
Much less occurrence of hypophosphatemia afterwards than with Injectafer.
However, Monoferric has been less studied in heart failure patients.

Since 2021, reimbursement has been possible in Belgium specifically for heart failure with reduced LVEF (HFrEF) if these criteria are met:

NYHA class II-IV.
Iron deficiency according to the definition above.
LVEF ≤ 40%.
The iron deficiency was investigated for all potentially treatable/reversible causes.

This reimbursement must be requested electronically by a cardiologist.