From the Guidelines
Iron supplementation is recommended for heart failure patients with iron deficiency, defined as ferritin levels below 100 μg/L or ferritin between 100-299 μg/L with transferrin saturation below 20%. This recommendation is based on the most recent and highest quality study, which demonstrated that intravenous iron therapy improves exercise capacity, quality of life, and reduces heart failure hospitalizations in patients with heart failure and iron deficiency 1.
Key Considerations
- Intravenous iron formulations like ferric carboxymaltose (Injectafer) or iron sucrose (Venofer) are preferred over oral supplements due to better absorption and efficacy.
- Treatment should be initiated regardless of anemia status, as iron deficiency alone contributes to heart failure symptoms.
- Iron supplementation improves exercise capacity, quality of life, and reduces heart failure hospitalizations by enhancing oxygen delivery, improving mitochondrial function, and reducing cardiac workload.
- Regular monitoring of iron parameters every 3-6 months is recommended to assess the need for additional treatment.
- Patients should be evaluated for underlying causes of iron deficiency such as gastrointestinal bleeding or malabsorption.
Evidence-Based Recommendations
The 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure recommends that intravenous iron replacement may be reasonable to improve functional status and quality of life in patients with NYHA class II and III HF and iron deficiency (ferritin <100 ng/mL or 100 to 300 ng/mL if transferrin saturation is <20%) 1.
Clinical Implications
The use of intravenous iron therapy in heart failure patients with iron deficiency has been shown to improve clinical outcomes, including exercise capacity and quality of life, and reduce hospitalizations due to worsening heart failure 1. Therefore, intravenous iron supplementation should be considered in symptomatic patients with heart failure and iron deficiency.
From the FDA Drug Label
See Table 1 for recommended dosage for treatment of iron deficiency in patients with heart failure and New York Heart Association class II/III to improve exercise capacity Table 1: Recommended Dosage in Patients with Iron Deficiency with Heart Failure Weight less than 70 kg Weight 70 kg or more Hb (g/dL) Hb (g/dL) < 10 < 10 10 to 14 10 to 14
14 to < 15 > 14 to < 15 Day 1 1,000 mg 1,000 mg 1,000 mg 1,000 mg 500 mg 500 mg Week 6 500 mg No dose No dose No dose 1,000 mg 500 mg 500 mg No dose Administer a maintenance dose of 500 mg at 12,24 and 36 weeks if serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL with transferrin saturation <20%.
The criteria for iron supplements in heart failure are based on the patient's weight and hemoglobin (Hb) levels.
- For patients with heart failure and New York Heart Association class II/III, the recommended dosage is outlined in Table 1.
- The dosage is administered intravenously, with a total cumulative dose of 1,500 mg of iron per course for patients weighing 50 kg or more.
- A maintenance dose of 500 mg may be administered at 12,24, and 36 weeks if certain conditions are met, such as low serum ferritin or transferrin saturation levels 2. Key considerations for iron supplements in heart failure include:
- Patient weight and Hb levels
- New York Heart Association class II/III
- Serum ferritin and transferrin saturation levels It is essential to follow the recommended dosage and administration guidelines to ensure safe and effective treatment 2 2.
From the Research
Criteria for Iron Supplements in Heart Failure
The criteria for iron supplements in heart failure are based on several studies that have investigated the relationship between iron deficiency and heart failure outcomes.
- Iron deficiency in heart failure is classically defined as ferritin < 100 µg/L or ferritin 100-300 µg/L and transferrin saturation < 20% 3.
- However, a recent study suggests that a low baseline transferrin saturation (TSAT) < 20%, rather than serum ferritin level, is a reliable indicator of the effect of intravenous iron to reduce major heart failure events 4.
- The European Society of Cardiology Guidelines for heart failure recommend a diagnostic work-up for iron deficiency in all heart failure patients and intravenous iron supplementation with ferric carboxymaltose for symptomatic patients with iron deficiency, defined by ferritin level less than 100 μg/l or by ferritin 100-300 μg/l with TSAT less than 20% 5.
- Other studies have also identified cutoff values for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin < 100 μg/l, or ferritin 100 to 300 μg/l, with transferrin saturation of < 20% 6.
Diagnosis and Treatment
- Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients 6.
- Intravenous iron products, such as ferric carboxymaltose, have been shown to have good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class 6.
- Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products 6.
- A new mechanism-based and trial-tested approach has been proposed, which defines an iron deficiency state in patients with heart failure as a TSAT < 20% (as long as the serum ferritin level is < 400 μg/L) 4.
Key Findings
- Randomized controlled trials have demonstrated that intravenous iron supplementation in heart failure patients with iron deficiency positively affects symptoms, quality of life, exercise tolerance, and hospitalization rates 3, 5, 6.
- The use of a serum ferritin level < 100 μg/L alone as a diagnostic criterion should be discarded, as it may lead to the treatment of many patients who are not iron deficient 4.