What is the recommended evaluation and management for an adult with new or worsening heart failure that appears to be driven by anemia?

Management of Heart Failure Due to Anemia

Screen all heart failure patients for anemia and iron deficiency at baseline, then treat iron deficiency with intravenous ferric carboxymaltose regardless of anemia status, while avoiding erythropoiesis-stimulating agents entirely. 1, 2

Initial Evaluation

Check these specific labs in every heart failure patient:

• Complete blood count to identify anemia (hemoglobin <13 g/dL in men, <12 g/dL in women) 2
• Serum ferritin and transferrin saturation to diagnose iron deficiency 1, 2
• Iron deficiency is defined as ferritin <100 μg/L OR ferritin 100-300 μg/L with transferrin saturation <20% 1, 2
• Additional workup: vitamin B12, folate, TSH, creatinine, and CRP to identify reversible causes 2
• Screen for occult gastrointestinal bleeding, particularly in patients on antiplatelet therapy 1

Treatment Algorithm for Iron Deficiency

For NYHA class II-III heart failure patients with confirmed iron deficiency (ferritin <100 μg/L or 100-300 μg/L with transferrin saturation <20%):

Intravenous Iron Therapy (Recommended)

Administer intravenous ferric carboxymaltose using weight-based and hemoglobin-based dosing: 3

For patients <70 kg:

• Hemoglobin <10 g/dL: 1,000 mg on day 1, then 500 mg at week 6 3
• Hemoglobin 10-14 g/dL: 1,000 mg on day 1 only 3
• Hemoglobin >14 to <15 g/dL: 500 mg on day 1 only 3

For patients ≥70 kg:

• Hemoglobin <10 g/dL: 1,000 mg on day 1, then 1,000 mg at week 6 3
• Hemoglobin 10-14 g/dL: 1,000 mg on day 1, then 500 mg at week 6 3
• Hemoglobin >14 to <15 g/dL: 500 mg on day 1 only 3

Administration details:

• Give as undiluted slow IV push at 100 mg per minute (for doses ≤750 mg) or over 15 minutes for 1,000 mg doses 3
• Alternatively, dilute in 250 mL normal saline (concentration ≥2 mg/mL) and infuse over ≥15 minutes 3
• Observe patients for 30 minutes post-injection for adverse reactions 4

Expected Benefits and Timeline

Symptom improvement occurs progressively: 4

• 4 weeks: Initial improvements in dyspnea, exercise capacity, and quality of life; approximately 50% of patients report feeling "much or moderately improved" 4
• 12 weeks: More robust functional capacity gains with continued improvement in 6-minute walk distance 4
• 24 weeks: Peak therapeutic benefit achieved; 47% of treated patients reach NYHA class I or II (versus 30% with placebo) 4
• 52 weeks: Sustained benefits in functional capacity, NYHA class, and quality of life 4

Clinical trial evidence demonstrates:

• Improved NYHA functional class, 6-minute walk test, and quality of life in FAIR-HF and CONFIRM-HF trials 1, 2
• Reduced heart failure hospitalizations 1
• Benefits occur in both anemic and non-anemic patients with iron deficiency 1
• No mortality benefit has been demonstrated, as trials were underpowered for this endpoint 1

Oral Iron (Not Recommended)

Do not use oral iron supplementation for heart failure patients with iron deficiency because of poor absorption and inability to replete iron stores adequately. 1, 2 The IRONOUT HF trial showed no improvement in exercise capacity with oral iron. 1

Monitoring and Maintenance

Re-evaluate iron status at 3 months after initial correction: 4

• Measure serum ferritin and transferrin saturation 4
• Administer maintenance dose of 500 mg ferric carboxymaltose at 12,24, and 36 weeks if ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 3
• Monitor for recurrent iron deficiency every 3 months for at least 1 year 2
• Check serum phosphate levels in patients requiring repeat courses within 3 months, as hypophosphatemia can occur 3

Expected hemoglobin response:

• An increase of ≥2 g/dL within 4 weeks indicates acceptable response 2

What NOT to Do

Erythropoiesis-Stimulating Agents (Contraindicated)

Do not use erythropoietin or darbepoetin in heart failure patients with anemia. 1 The largest randomized trial (n=2,278) showed:

• No improvement in clinical outcomes 1
• Significant increase in thromboembolic events 1
• Nonsignificant increase in fatal and nonfatal strokes 1

This represents a Class III (Harm) recommendation with moderate-quality evidence. 1

Blood Transfusions

Use restrictive transfusion strategy (hemoglobin threshold 7-8 g/dL) in hospitalized heart failure patients with coronary disease. 1 Liberal transfusion strategies do not improve outcomes and may cause harm. 1

Important Caveats

Safety considerations for IV iron:

• Safety unknown in patients with hemoglobin >15 g/dL; no dosing data available beyond this threshold 1, 3
• Monitor for extravasation during administration, as brown discoloration can be long-lasting 3
• No data available to guide dosing beyond 36 weeks 3

Evidence limitations:

• Trials were underpowered to detect mortality benefit 1
• No data specifically for HFpEF or HFmrEF populations 1
• Long-term safety beyond 52 weeks remains unknown 1

The strength of recommendation for IV iron is Class IIa (reasonable to consider) rather than Class I because definitive morbidity and mortality trials are still pending. 1 However, the consistent improvements in functional capacity, quality of life, and hospitalizations across multiple trials support its use in symptomatic patients with iron deficiency.