What is the significance of iron deficiency in patients with Congestive Heart Failure (CHF)?

From the Guidelines

Iron deficiency is a significant complication in congestive heart failure (CHF) patients that requires prompt identification and treatment, with intravenous iron supplementation being the most effective treatment option, as evidenced by studies such as 1 and 1.

Key Points

• Iron deficiency affects approximately 40-70% of CHF patients and is associated with worse symptoms, reduced exercise capacity, poorer quality of life, and increased hospitalization rates, even without anemia, as noted in 1.
• Treatment involves intravenous iron supplementation, with ferric carboxymaltose being a commonly used option, typically administered as 500-1000mg infusions based on body weight and hemoglobin levels, as seen in 1 and 1.
• Oral iron supplements are generally ineffective due to poor absorption and gastrointestinal side effects in CHF patients, as highlighted in 1.
• Iron is essential for oxygen transport, energy production in cardiac muscle cells, and proper functioning of enzymes involved in cellular respiration, with chronic inflammation in CHF impairing iron absorption and utilization through increased hepcidin levels, as discussed in 1 and 1.
• Regular screening for iron deficiency in CHF patients is recommended using ferritin and transferrin saturation measurements, with deficiency defined as ferritin <100 μg/L or ferritin 100-299 μg/L with transferrin saturation <20%, as recommended in 1 and 1.
• Correcting iron deficiency can improve heart failure symptoms, exercise capacity, and quality of life even when anemia is not present, as demonstrated in studies such as 1 and 1.

Recommendations

• Intravenous iron supplementation should be considered for all CHF patients with iron deficiency, regardless of the presence of anemia, as supported by 1, 1, and 1.
• Regular screening for iron deficiency should be performed in all CHF patients, using ferritin and transferrin saturation measurements, as recommended in 1 and 1.
• Oral iron supplements should not be used as a first-line treatment for iron deficiency in CHF patients, due to their poor efficacy and tolerability, as noted in 1.

From the FDA Drug Label

Trial 3: FER-CARS-05 (CONFIRM-HF) was a randomized, double-blind, placebo-controlled, study in patients with iron deficiency and chronic heart failure with left ventricular ejection fraction of < 45% and New York Heart Association (NYHA) class II/III to determine whether intravenous Injectafer improves exercise capacity measured as change from baseline to 24 weeks in 6-minute walk distance (6MWD). Iron deficiency was defined as serum ferritin <100 ng/mL or 100 to 300 ng/mL with TSAT <20%. The mean change in 6MWD from Baseline to Week 24 in Injectafer-treated patients was 18 meters (95% CI 4,32), and placebo-treated patients was -7 meters (95% CI -21,7), with between group difference of 25 meters (7,43), p-value 0. 007, favoring Injectafer.

The significance of iron deficiency in patients with Congestive Heart Failure (CHF) is that correcting it with intravenous iron therapy, such as ferric carboxymaltose, can improve exercise capacity as measured by the 6-minute walk distance (6MWD) 2.

• Key findings include:
  • Improved 6MWD in iron-deficient CHF patients treated with intravenous iron
  • Increased serum ferritin and transferrin saturation (TSAT) levels in treated patients
  • Positive effect on hemoglobin (Hb) levels in treated patients The study suggests that iron deficiency is a significant factor in CHF patients and that correcting it can have a positive impact on their condition 2.

From the Research

Significance of Iron Deficiency in CHF

• Iron deficiency is a common comorbidity in patients with Congestive Heart Failure (CHF), affecting approximately 50% of patients with stable heart failure, regardless of left ventricular function 3, 4.
• The presence of iron deficiency in CHF patients is associated with reduced functional capacity, lower quality of life, and an increased risk of hospitalizations and mortality, independent of anemia 3, 5, 4.

Diagnosis and Treatment of Iron Deficiency in CHF

• Timely diagnosis and treatment of iron deficiency are essential to improve clinical outcomes in CHF patients 3.
• Parenteral iron supplementation has been established as an important complementary therapy to improve patient well-being and physical performance in CHF patients with iron deficiency 4.
• Intravenous iron preparations, such as ferric carboxymaltose, have demonstrated superior clinical effects compared to oral iron preparations in improving symptoms, exercise capacity, and quality of life in CHF patients 4.

Prevalence and Management of Iron Deficiency in Hospitalized CHF Patients

• Iron deficiency remains under-recognized and undertreated in clinical practice among hospitalized CHF patients, with only 74% of patients having their iron status checked, and 65% of iron-deficient patients receiving iron replacement therapy 6.
• The presence of iron deficiency in hospitalized CHF patients is associated with longer hospital stays and increased morbidity and mortality 6.

Ongoing Research and Future Directions

• There is a need for increased awareness, education, and practical guidance to improve the screening, diagnosis, and management of iron deficiency in CHF patients 6, 4.
• Ongoing trials are investigating the effect of iron therapy on morbidity and mortality in CHF patients with iron deficiency, including those with preserved ejection fraction 7, 4.