In a patient with valvular heart disease presenting with anemia symptoms (fatigue, reduced exercise tolerance, or heart failure), should ferritin be screened and how should low or high ferritin levels be managed?

Ferritin Screening and Management in Valvular Heart Disease with Anemia

All patients with valvular heart disease presenting with anemia symptoms should be screened for iron deficiency using both ferritin and transferrin saturation (TSAT), and those with iron deficiency (ferritin <100 ng/mL or ferritin 100-300 ng/mL with TSAT <20%) should receive intravenous iron therapy to improve functional capacity and quality of life. 1

Screening Recommendations

Routine baseline assessment of all patients with heart failure—including those with valvular heart disease—must include evaluation for both anemia and iron deficiency. 1

Required Laboratory Tests

• Ferritin and TSAT must be measured simultaneously and interpreted together, as neither marker alone reliably identifies iron deficiency in the setting of heart disease 1
• Complete blood count to assess hemoglobin levels and severity of anemia 1
• Serum iron and total iron-binding capacity (TIBC) to calculate TSAT 1
• C-reactive protein to identify inflammatory states that may elevate ferritin 2

Diagnostic Thresholds for Iron Deficiency

Iron deficiency in heart failure is defined as: 1

• Ferritin <100 ng/mL (regardless of TSAT), OR
• Ferritin 100-300 ng/mL with TSAT <20%

The most recent evidence suggests that TSAT <20% is the most reliable marker of true iron deficiency in heart failure patients, as it directly reflects hypoferremia and iron-deficient erythropoiesis, whereas ferritin can be falsely elevated by inflammation 3. Patients with TSAT ≥20% and ferritin 20-100 ng/mL are generally not iron deficient and do not respond favorably to iron therapy 3.

Management of Low Ferritin/Iron Deficiency

Intravenous Iron Therapy

Intravenous iron is the only effective route for iron repletion in heart failure patients with iron deficiency. 1

Evidence Base

• The FAIR-HF trial demonstrated significant improvements in NYHA class, 6-minute walk test, and quality of life with weekly intravenous ferric carboxymaltose, independent of the presence of anemia 1
• The CONFIRM-HF trial confirmed sustained improvements in exercise capacity over 52 weeks and showed a reduction in heart failure hospitalizations 1
• The AFFIRM-AHF trial in hospitalized heart failure patients (EF <50%) demonstrated a 26% reduction in heart failure hospitalizations (RR 0.74; 95% CI 0.58-0.94) 1

Why Oral Iron Fails

Oral iron supplementation is inadequate and should not be used in heart failure patients with iron deficiency 1. The IRONOUT HF trial showed no improvement with oral iron, attributed to poor absorption and hepcidin-mediated blockade of intestinal iron uptake in the inflammatory state of heart failure 1.

Dosing Protocol

Ferric carboxymaltose dosing: 1

• Calculate total iron need based on hemoglobin and body weight
• Administer single doses of 500-1000 mg iron
• Do not administer if hemoglobin >15 g/dL 1

Dosing by hemoglobin and weight: 1

• Hb <10 g/dL: 500 mg (<35 kg), 1500 mg (35-70 kg), 2000 mg (≥70 kg)
• Hb 10-14 g/dL: 500 mg (<35 kg), 1000 mg (35-70 kg), 1500 mg (≥70 kg)
• Hb 14-15 g/dL: 500 mg (all weights)

Monitoring After Treatment

• Recheck ferritin and TSAT at the next scheduled visit, preferably after 3 months 1
• Do not measure iron parameters within 4 weeks of IV iron infusion, as circulating iron interferes with assay accuracy 1, 2
• Optimal reassessment window is 4-8 weeks after the last infusion 2
• Continue monitoring ferritin and TSAT 1-2 times per year or if clinical picture changes or hemoglobin decreases 1

Treatment Goals

Target TSAT ≥20% after iron repletion to ensure adequate iron availability for erythropoiesis 1, 2

Management of High Ferritin

Interpretation in Context

Ferritin is an acute-phase reactant and can be falsely elevated in inflammatory states, chronic disease, or with certain medications (neprilysin inhibitors, SGLT2 inhibitors) 3.

Functional Iron Deficiency

Even with ferritin 100-300 ng/mL, patients may have functional iron deficiency if TSAT <20% 1, 2. This reflects hepcidin-mediated sequestration of iron in storage sites, making it unavailable for erythropoiesis despite adequate total body iron stores 2.

These patients still benefit from intravenous iron therapy because it bypasses the hepcidin blockade and directly delivers iron to the bone marrow 1, 2.

True Iron Overload

Ferritin >300 ng/mL with TSAT >50% suggests true iron overload 2. In this scenario:

• Investigate for hemochromatosis or other iron-loading conditions
• Do not administer additional iron
• Consider hematology consultation

Common Pitfalls to Avoid

• Never rely on ferritin alone in heart failure patients, as inflammation distorts interpretation; always measure TSAT concurrently 1, 3
• Do not use oral iron in heart failure patients with iron deficiency—it is ineffective due to hepcidin-mediated intestinal blockade 1
• Do not measure iron parameters too early after IV iron administration (wait at least 4 weeks) to avoid falsely elevated results 1, 2
• Do not withhold IV iron from non-anemic patients with iron deficiency—the FAIR-HF trial showed benefit independent of anemia status 1
• Mean corpuscular volume and serum iron alone are unreliable markers and should not be used to assess iron status 1

Clinical Algorithm

1. Screen all valvular heart disease patients with anemia symptoms for iron deficiency using ferritin and TSAT 1

2. Diagnose iron deficiency if:

   • Ferritin <100 ng/mL (any TSAT), OR
   • Ferritin 100-300 ng/mL with TSAT <20% 1

3. Administer intravenous ferric carboxymaltose (dose based on hemoglobin and weight) 1

4. Reassess iron parameters 3 months after treatment (not before 4 weeks) 1, 2

5. Continue monitoring 1-2 times yearly or with clinical changes 1

6. Target TSAT ≥20% to ensure adequate iron for red cell production 1, 2