Too Much, Too Little, or Just Right?: Untangling Endogenous Erythropoietin in Heart Failure

Abstract

“Why then, can one desire too much of a good thing?” — —William Shakespeare, As You Like It, Act IV Anemia is common in patients with heart failure and is associated with adverse outcomes. This observation has now been replicated in chronic systolic heart failure,1 heart failure with preserved ejection fraction,2 and acute decompensated heart failure.3 These data have led to the hypotheses that treating anemia in patients with heart failure may improve outcomes, and therapeutic trials of both the erythropoietin-stimulating agent darbepoetin4 and intravenous iron5 in heart failure are currently ongoing. Despite the accumulation of data on the potential importance of anemia in heart failure, much about the pathophysiology of this association remains poorly understood. Article see p 245 What explains the high prevalence of anemia in heart failure? In addressing this issue, it is important to recognize that anemia in heart failure not a single clinical entity, and there are numerous potential contributors to anemia in this population. First, previous data in patients with advanced heart failure indicate that approximately half of patients with low hemoglobin have hemodilution rather than a true decrease in red blood cell mass.6 Iron deficiency may contribute to anemia in heart failure patients, although the true prevalence of iron deficiency in heart failure remains uncertain, and published estimates have varied widely.7,8 Regardless of whether frank iron deficiency exists, there seems to be a functional iron deficiency in many patients with heart failure and anemia associated with impaired ability to utilize available iron stores.8 The combination of systemic inflammation, blunted bone marrow responsiveness to erythropoietin, and impaired iron mobilization is consistent with anemia of …