Management of Anemia and Iron Deficiency in Heart Failure

Abstract

Anemia is independently associated with an increased risk of mortality and morbidity in patients with heart failure (HF). The diagnosis of anemia should prompt assessment of the underlying cause(s), first by using routine laboratory measurements (i.e., serum creatinine and estimated glomerular filtration rate [eGFR], serum iron, transferrin saturation, ferritin, vitamin B12, folic acid, and thyroid stimulating hormone). In clinical practice, it remains unclear whether using levels of the soluble transferrin receptor in HF patients to assess iron deficiency is warranted. Further investigation should follow these simple tests when judged appropriate (e.g., if occult gastrointestinal blood losses are suspected). Hemodilution may contribute significantly to anemia in patients with advanced HF and may be suspected when signs of hypervolemia are present. Euvolemia should be the first goal in such cases (as always), followed by optimization of the disease-modifying therapies used in HF (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, or aldosterone antagonists and cardiac resynchronization therapy in selected cases). Erythropoiesis-stimulating agents (ESA) can be used to improve functional capacity in patients with significant chronic kidney disease (CKD), a frequent comorbidity in HF patients. ESA and iron therapy is recommended in patients with moderate-to-severe CKD (eGFR < 60mL/min/1.73m(2)), with a target hemoglobin level of 11.0g/dL. In a recent randomized, placebo-controlled clinical trial, weekly administration of intravenous iron significantly improved symptoms, New York Heart Association class, quality of life, and exercise capacity in both anemic and non-anemic HF patients. A trend toward fewer hospitalizations was seen in the group treated with intravenous iron. The rates of adverse events were similar in the treatment and the placebo groups. Larger-scale and longer-term studies are needed to establish the safety and efficacy profile of intravenous iron in non-CKD HF patients and in HF patients without anemia. Studies designed to further unravel the pathophysiology of anemia in HF are essential in order to determine 1) novel treatment targets and 2) whether and how the treatment of anemia could improve outcomes.