Faculty Bibliography

Iron deficiency is a common cause of anemia in otherwise healthy individuals and plays an important role in the development of anemia within the heart failure patient population. Iron-deficient heart failure patients experience worse symptoms and are less exercise tolerant than those without iron deficiency. These symptoms may occur even before clinical anemia is evident. This article reviews studies of the benefits of the use of intravenous iron to treat iron deficiency in anemic and nonanemic heart failure patients and an overview of the physiology and pathophysiology of iron metabolism in chronic heart failure

Iron-deficiency anemia is common in patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a subgroup analysis also suggest that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients

BACKGROUND:Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction (MI). METHODS:We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute MI treated with aspirin and clopidogrel after successful percutaneous coronary intervention. RESULTS:Recombinant human erythropoietin did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMCs when compared with placebo (all Ps < .05). CONCLUSIONS:In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMCs when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials.

In August 2003, the Minority Health Institute (MHI) convened an Expert Advisory Panel of cardiologists and urologists to design a new practice model algorithm that uses erectile dysfunction (ED) as a clinical tool for early identification of men with systemic vascular disease. The MHI algorithm noted ED as a marker for the presence of cardiovascular disease and suggested that ED may well be a cardiovascular risk equivalent warranting aggressive secondary prevention management strategies, even in the absence of other cardiac or peripheral vascular symptoms. The MHI algorithm stipulates that all men 25 years of age and older should be asked about ED as a routine part of the cardiovascular history during any office visit. The presence of ED should prompt an aggressive assessment for occult vascular disease; many men with erectile difficulty would benefit from early, aggressive management of cardiovascular risk factors with both lifestyle modification and pharmacotherapy to achieve optimal target goals under the existing treatment guidelines. Since publication of the algorithm in 2005, additional research studies have further supported the advisory panel recommendations

This review article summarizes the current medical literature reporting on the prevalence and prognostic significance of anemia in patients with heart failure. Almost all currently available data indicate that anemia is common in heart failure populations, with the majority of studies indicating prevalence >20%. Anemia appears to be more highly prevalent in patients with advanced age, with more severe limitations in functional capacity, and with greater severity of co-morbid chronic kidney disease. In most reported studies anemia is an independent predictor of increased mortality risk and increased risk of hospitalization for heart failure. These data provide the rationale for interventional treatment trials to determine if anemia is in the causal pathway for disease progression and increased mortality risk in HF patients

Based on the findings of retrospective studies, there has been growing interest in the potential therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients with heart failure. The first published prospective randomized study of statins in heart failure patients did not demonstrate improved clinical outcomes (death and nonfatal myocardial infarction or stroke) after treatment with 10 mg daily of rosuvastatin when compared with placebo. However, use of rosuvastatin was associated with a reduced risk of hospitalization when compared with placebo and was well tolerated. Until further information becomes available, routine use of statins is not recommended in the heart failure population

Accurate individual norms are required for blood volume measurement to be useful in a clinical setting. The primary physiological determinant of normal blood volume is body composition. Norms have been developed based on weight and body surface area, but these have systematic errors arising from variations in body composition or body size. The only norm that specifically estimates body composition uses deviation from ideal weight. A clinically useful norm must also include a normal range that is sufficiently sensitive and specific. The ultimate test of a norm's effectiveness is how it relates to known physiological factors or outcomes in a clinical or research setting. When tested in relation to outcome results from previously published clinical studies, norms utilizing deviation from ideal weight provide the most accurate categorization of blood volume status.