How should iron deficiency be managed in patients with heart failure?

Management of Iron Deficiency in Heart Failure

All symptomatic patients with heart failure and reduced ejection fraction (HFrEF, LVEF <40%) who have iron deficiency should receive intravenous ferric carboxymaltose or ferric derisomaltose to improve exercise capacity, quality of life, and reduce hospitalizations. 1

Screening and Diagnosis

Who to Screen

• Screen all newly diagnosed heart failure patients for iron deficiency as part of initial diagnostic workup (Class I recommendation from the European Society of Cardiology). 1, 2
• Re-evaluate iron status in existing heart failure patients who remain symptomatic despite optimal medical therapy. 1
• Consider routine monitoring 1-2 times per year in all known heart failure patients, and after any hospitalization for heart failure. 1

Diagnostic Criteria

Iron deficiency in heart failure is defined by either: 1, 2

• Absolute deficiency: Serum ferritin <100 μg/L
• Functional deficiency: Serum ferritin 100-299 μg/L with transferrin saturation (TSAT) <20%

Important caveat: Iron deficiency affects 40-70% of chronic heart failure patients and worsens outcomes independent of whether anemia is present. 1, 2 Do not wait for anemia to develop before screening or treating.

Treatment Approach

Indications for Intravenous Iron

Intravenous iron therapy (Class IIa recommendation, Level A evidence) is indicated for: 1

• Symptomatic patients with chronic HFrEF (LVEF <40%)
• NYHA functional class II or III
• Iron deficiency by the above criteria
• Hemoglobin ≤15 g/dL 1

Which Iron Preparation

Use intravenous ferric carboxymaltose (FCM) or ferric derisomaltose—oral iron has NOT been shown effective in heart failure patients. 1, 3

The FDA-approved ferric carboxymaltose demonstrated in the CONFIRM-HF trial a 25-meter improvement in 6-minute walk distance at 24 weeks compared to placebo (p=0.007). 4

Dosing Protocol

For patients ≥50 kg: 1, 4

• 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course)
• Alternative: Single dose of 15 mg/kg (maximum 1,000 mg) per course

For patients <50 kg: 1, 4

• 15 mg/kg IV in two doses separated by at least 7 days

Maximum weekly dose: 1,000 mg iron per week. 1

Administration Details

• Can be given as undiluted slow IV bolus injection (100 mg/min, or 15 minutes for 1,000 mg dose) or as diluted infusion. 1
• Observe patients for at least 30 minutes after each injection for hypersensitivity reactions. 1, 4
• Can be administered in hospital or community settings where staff are trained to manage hypersensitivity reactions. 1

Monitoring

Post-Treatment Assessment

• Re-evaluate iron status at 3 months after initial correction dose, not earlier. 1
• Avoid checking iron status within 4 weeks of IV iron administration—ferritin levels increase markedly and cannot accurately reflect iron status during this period. 1
• Provide additional iron repletion as needed based on 3-month reassessment. 1

Expected Improvements

Clinical trials demonstrate that IV iron therapy improves: 1, 3

• Exercise capacity (6-minute walk test distance)
• Peak oxygen consumption
• NYHA functional class
• Quality of life scores
• Reduces heart failure hospitalizations

Critical limitation: Current trials were not powered to evaluate mortality benefit, so survival advantage has not been demonstrated. 1

Contraindications and Cautions

Absolute Contraindications 1, 4

• Hypersensitivity to ferric carboxymaltose or any excipients
• Known serious hypersensitivity to other parenteral iron products
• Anemia not due to iron deficiency
• Evidence of iron overload

Use With Caution 1

• Stop treatment in patients with active bacteremia—use cautiously in acute or chronic infection
• Patients with drug allergies, severe asthma, eczema, or atopic allergies (increased hypersensitivity risk)
• Immune/inflammatory conditions (SLE, rheumatoid arthritis)
• Monitor for symptomatic hypophosphatemia in patients requiring repeat courses 4
• Monitor blood pressure—hypertension can occur 4

Evidence Gaps

• No clinical evidence for IV iron in HFpEF (LVEF ≥50%) and limited evidence in HFmrEF (LVEF 40-49%). 1
• Efficacy and safety not evaluated in patients with hemoglobin >15 g/dL. 1

Pathophysiology Context

Iron deficiency in heart failure results from: 1, 2

• Absolute deficiency: Malabsorption, malnutrition, GI blood loss (exacerbated by anticoagulants, antiplatelets, NSAIDs)
• Functional deficiency: Chronic inflammation elevates hepcidin, which blocks intestinal iron absorption and mobilizes iron from storage sites, despite adequate total body stores

This iron-restricted state impairs skeletal muscle function, cardiac muscle performance, renal function, and immune system function, contributing to the reduced exercise capacity and poor quality of life seen in these patients. 2, 5