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STATE-OF-THE-ART PAPER

Anemia and Chronic Heart Failure

Implications and Treatment Options

VA Medical Center and University of Minnesota Medical School, Minneapolis, Minnesota.

Manuscript received January 31, 2008; revised manuscript received April 9, 2008, accepted April 16, 2008.

^_* Reprint requests and correspondence: Dr. Inder S. Anand, Director, Heart Failure Program, VA Medical Center, Mail Stop 111C, One Veterans Drive, Minneapolis, Minnesota 55417. (Email: anand001{at}umn.edu).

Anemia is a common comorbidity in patients with heart failure and is associated with worse long-term outcomes. Although the cause of anemia in heart failure is unclear, the weight of evidence suggests that renal dysfunction, along with neurohormonal and proinflammatory cytokine activation in heart failure, favors the development of anemia of chronic disease, with defective iron utilization, inappropriate erythropoietin production, and depressed bone marrow function. Similarly, the mechanisms by which anemia worsens heart failure outcomes are unknown but may be related to increased myocardial workload. If anemia is a mediator and not just a marker of poor outcomes, correcting anemia could become an important and novel therapeutic target to improve long-term outcomes in such patients. Indeed, several small-sized studies have shown the beneficial effects of empirically treating anemia in heart failure patients with recombinant erythropoietin and intravenous iron. However, the ideal threshold at which therapy should be initiated and the extent of correction considered safe and desirable in the individual patient with heart failure need to be known. These issues become more important because of increasing safety concerns that recombinant erythropoietin therapy for treating anemia may be associated with adverse cardiovascular outcomes in patients with chronic kidney disease and may worsen cancer in patients receiving chemotherapy to treat various types of cancer. Therefore, further prospectively designed studies are required to address some of these questions. Fortunately, 2 large mortality morbidity trials, TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) in patients with chronic kidney disease and RED-HF (Reduction of Events with Darbepoetin alfa in Heart Failure) in heart failure patients, are in progress and are likely to provide definitive answers.

Key Words: anemia • heart failure • chronic kidney disease • erythropoietin

Abbreviations and Acronyms   BNP = brain natriuretic peptide   BP = blood pressure   CKD = chronic kidney disease   CRP = C-reactive protein   EF = ejection fraction   ESA = erythropoietin-stimulating agents   Hct = hematocrit   HF = heart failure   Hgb = hemoglobin   IL = interleukin   IV = intravenous   LV = left ventricular   MLHFQ = Minnesota Living with Heart Failure Questionnaire   RBF = renal blood flow   SVR = systemic vascular resistance

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