Erythropoietin Therapy for Heart Failure

  • Margarita Borovka
  • Mathew S. MaurerEmail author


Erythropoietin is a growth factor that is the main stimulus for erythrocyte production. Because anemia is recognized as a common comorbidity in older adult patients with heart failure, the use of erythropoietin within this cohort has been embraced as a potential therapy for improving outcomes including quality of life. Clinical trials of erythropoietin in systolic heart failure have demonstrated several positive effects of the drug on cardiovascular structure and function and exercise capacity. However, the promising results of these studies are often offset by small sample sizes, absence of enrollment of patients > 75 years of age, those with preserved ejection fraction heart failure (HFPEF), and the potential for serious adverse side effects. The pleiotropic effects of erythropoietin therapy including both hematopoietic and non-hematopoietic actions are relevant especially for older adults with HFPEF in whom multiple mechanisms produce the observed phenotype and for whom the adverse effects of therapy are heightened. The successes of erythropoietin administration within the older adult heart failure population remain to be tested in large clinical trials that will provide clear evidence of safety and efficacy. For such trials, we highlight erythropoietin dosing, implementation of run-in periods, and methods to identify the group of older adults, particularly susceptible to erythropoietin’s side effects, who are poor responders to the drug. Collectively, such information is essential to adequately delineate the role of erythropoietin therapy within the aging heart failure population.


Chronic Kidney Disease Chronic Kidney Disease Patient Hypoplastic Left Heart Syndrome Systolic Heart Failure Heart Failure Population 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ng T, Marx G, Littlewood T, Macdougall I. Recombinant erythropoietin in clinical practice. Postgrad Med J. 2003;79:367–76.PubMedCrossRefGoogle Scholar
  2. 2.
    Bert P. Sur la richesse en hemoglobine du sang des animaux vivant sur les hauts lieux. C R Acad Sci Paris. 1882;94:805–7.Google Scholar
  3. 3.
    Bonsdorff E, Jalavisto E. A humoral mechanism in anoxic erythrocytosis. Acta Physiol Scand. 1948;16:150–70.CrossRefGoogle Scholar
  4. 4.
    Reissmann KR. Studies on the mechanism of erythropoietic stimulation in parabiotic rats during hypoxia. Blood. 1950;5:372–80.PubMedGoogle Scholar
  5. 5.
    Ruhenstroth-Bauer G. Reticulocyte and erythrocyte longevity. Klin Wochenschr. 1950;28:780–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Ruhenstroth-Bauer G. [Experiments in the identification of a specific erythropoietic hormone]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1950;211:32–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Miyake T, Kung CK, Goldwasser E. Purification of human erythropoietin. J Biol Chem. 1977;252:5558–64.PubMedGoogle Scholar
  8. 8.
    II THM. Eugene Goldwasser dies at 88; biochemist was known for anemia drug. In: Los Angeles Times. Los Angeles: Los Angeles Times; 2010.Google Scholar
  9. 9.
    Lin FK, Suggs S, Lin CH, et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985;82:7580–4.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10. U.S. National Institutes of Health. Last Accessed 10 Oct 2012Google Scholar
  11. 11.
    Goodnough LT, Anderson KC, Kurtz S, et al. Indications and guidelines for the use of hematopoietic growth factors. Transfusion. 1993;33:944–59.PubMedCrossRefGoogle Scholar
  12. 12.
    Wu H, Liu X, Jaenisch R, Lodish HF. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell. 1995;83:59–67.PubMedCrossRefGoogle Scholar
  13. 13.
    Koury MJ, Bondurant MC. The molecular mechanism of erythropoietin action. Eur J Biochem/FEBS. 1992;210:649–63.CrossRefGoogle Scholar
  14. 14.
    Lombardero M, Kovacs K, Scheithauer BW. Erythropoietin: a hormone with multiple functions. Pathobiology: J Immunopathol Mol Cell Biol. 2011;78:41–53.CrossRefGoogle Scholar
  15. 15.
    Jacobson LO, Goldwasser E, Fried W, Plzak L. Role of the kidney in erythropoiesis. Nature. 1957;179:633–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Wenger RH, Hoogewijs D. Regulated oxygen sensing by protein hydroxylation in renal erythropoietin-producing cells. Am J Physiol Renal Physiol. 2010;298:F1287–96.PubMedCrossRefGoogle Scholar
  17. 17.
    Fried W. The liver as a source of extrarenal erythropoietin production. Blood. 1972;40:671–7.PubMedGoogle Scholar
  18. 18.
    Leong CL, Anderson WP, O'Connor PM, Evans RG. Evidence that renal arterial-venous oxygen shunting contributes to dynamic regulation of renal oxygenation. Am J Physiol Renal Physiol. 2007;292:F1726–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Brienza N, Giglio MT, Marucci M. Preventing acute kidney injury after noncardiac surgery. Curr Opin Crit Care. 2010;16:353–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Rhoades RA, Bell DR, editors. Medical Physiology Principles for Clinical Medicine. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012.Google Scholar
  21. 21.
    Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A. 1998;95:11715–20.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Ershler WB, Sheng S, McKelvey J, et al. Serum erythropoietin and aging: a longitudinal analysis. J Am Geriatr Soc. 2005;53:1360–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Barrett KE, BSe, Boitano S, Brooks HL, editors. Ganong's review of medical physiology. 24 ed. New York: McGraw-Hill; 2012.Google Scholar
  24. 24.
    Adamson JW, Longo DL. Anemia and polycythemia. In: Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo, editors. Harrison's principles of internal medicine. 18 ed. New York: McGraw-Hill; 2012.Google Scholar
  25. 25.
    Sherwood L, editor. Human physiology: from cells to systems. 7 ed. Brooks Cole; 2008. P. 397.Google Scholar
  26. 26.
    Lundby C, Thomsen JJ, Boushel R, et al. Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J Physiol. 2007;578:309–14.PubMedCrossRefGoogle Scholar
  27. 27.
    Krapf R, Hulter HN. Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). Clin J Am Soc Nephrol: CJASN. 2009;4:470–80.PubMedCrossRefGoogle Scholar
  28. 28.
    de Simone G, Devereux RB, Chien S, Alderman MH, Atlas SA, Laragh JH. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation. 1990;81:107–17.PubMedCrossRefGoogle Scholar
  29. 29.
    Lundby C, Robach P, Boushel R, et al. Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport? J Appl Physiol. 2008;105:581–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Meister B, Maurer H, Simma B, et al. The effect of recombinant human erythropoietin on circulating hematopoietic progenitor cells in anemic premature infants. Stem Cells. 1997;15:359–63.PubMedCrossRefGoogle Scholar
  31. 31.
    Ganser A, Bergmann M, Volkers B, Grutzmacher P, Scigalla P, Hoelzer D. In vivo effects of recombinant human erythropoietin on circulating human hematopoietic progenitor cells. Exp Hematol. 1989;17:433–5.PubMedGoogle Scholar
  32. 32.
    Geissler K, Stockenhuber F, Kabrna E, Hinterberger W, Balcke P, Lechner K. Recombinant human erythropoietin and hematopoietic progenitor cells in vivo. Blood. 1989;73:2229.PubMedGoogle Scholar
  33. 33.
    Stohlawetz PJ, Dzirlo L, Hergovich N, et al. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood. 2000;95:2983–9.PubMedGoogle Scholar
  34. 34.
    Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res. 2004;63:208–16.PubMedCrossRefGoogle Scholar
  35. 35.
    Kertesz N, Wu J, Chen TH, Sucov HM, Wu H. The role of erythropoietin in regulating angiogenesis. Dev Biol. 2004;276:101–10.PubMedCrossRefGoogle Scholar
  36. 36.
    Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002;106:2973–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Fliser D, Bahlmann FH. Erythropoietin and the endothelium - a promising link? Eur J Clin Invest. 2008;38:457–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Suzuki N, Ohneda O, Takahashi S, et al. Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood. 2002;100:2279–88.PubMedCrossRefGoogle Scholar
  39. 39.
    Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML. Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development. 1999;126:3597–605.PubMedGoogle Scholar
  40. 40.
    Yu X, Lin CS, Costantini F, Noguchi CT. The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse. Blood. 2001;98:475–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Lakatta EG. Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail Rev. 2002;7:29–49.PubMedCrossRefGoogle Scholar
  42. 42.
    Pollack M, Phaneuf S, Dirks A, Leeuwenburgh C. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann N Y Acad Sci. 2002;959:93–107.PubMedCrossRefGoogle Scholar
  43. 43.
    Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;68:1560–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Gerstenblith G, Frederiksen J, Yin FC, Fortuin NJ, Lakatta EG, Weisfeldt ML. Echocardiographic assessment of a normal adult aging population. Circulation. 1977;56:273–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Thomas L, Levett K, Boyd A, Leung DY, Schiller NB, Ross DL. Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable? J Am Coll Cardiol. 2002;40:1630–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Parsa CJ, Matsumoto A, Kim J, et al. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest. 2003;112:999–1007.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Kleijn L, de Boer RA, Voors AA. Should erythropoietin treatment in chronic heart failure be haemoglobin targeted? Eur J Heart Fail. 2010;12:215–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Lu Y, Zhou J, Xu C, et al. JAK/STAT and PI3K/AKT pathways form a mutual transactivation loop and afford resistance to oxidative stress-induced apoptosis in cardiomyocytes. Cell Physiol Biochem: Int J Exp Cell Physiol Biochem Pharmacol. 2008;21:305–14.CrossRefGoogle Scholar
  49. 49.
    Mitchell GF, Verwoert GC, Tarasov KV, et al. Common genetic variation in the 3′-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. Circ Cardiovasc Genet. 2012;5:81–90.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    van der Meer P, Lipsic E, Henning RH, et al. Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol. 2005;46:125–33.PubMedCrossRefGoogle Scholar
  51. 51.
    Westenbrink BD, Ruifrok WP, Voors AA, et al. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure. Cardiovasc Res. 2010;87:30–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Li Y, Takemura G, Okada H, et al. Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res. 2006;71:684–94.PubMedCrossRefGoogle Scholar
  53. 53.
    Kinugawa S, Tsutsui H, Hayashidani S, et al. Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress. Circ Res. 2000;87:392–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Testa M, Yeh M, Lee P, et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996;28:964–71.PubMedCrossRefGoogle Scholar
  55. 55.
    Ikeuchi M, Tsutsui H, Shiomi T, et al. Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction. Cardiovasc Res. 2004;64:526–35.PubMedCrossRefGoogle Scholar
  56. 56.
    Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Ludman AJ, Yellon DM, Hasleton J, et al. Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial. Heart. 2011;97:1560–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Bergmann MW, Haufe S, von Knobelsdorff-Brenkenhoff F, et al. A pilot study of chronic, low-dose epoetin-{beta} following percutaneous coronary intervention suggests safety, feasibility, and efficacy in patients with symptomatic ischaemic heart failure. Eur J Heart Fail. 2011;13:560–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001;101:271–6.PubMedGoogle Scholar
  60. 60.
    Hasselblatt M, Ehrenreich H, Siren AL. The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol. 2006;18:132–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Sakanaka M, Wen TC, Matsuda S, et al. In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A. 1998;95:4635–40.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation. Proc Natl Acad Sci U S A. 1997;94:343–50.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Sadamoto Y, Igase K, Sakanaka M, et al. Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun. 1998;253:26–32.PubMedCrossRefGoogle Scholar
  64. 64.
    Junk AK, Mammis A, Savitz SI, et al. Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2002;99:10659–64.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Celik M, Gokmen N, Erbayraktar S, et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A. 2002;99:2258–63.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Kumar R, Jaggi AS, Singh N. Effects of erythropoietin on memory deficits and brain oxidative stress in the mouse models of dementia. Korean J Physiol Pharmacol: Off J Korean Physiol Soc Korean Soc Pharmacol. 2010;14:345–52.CrossRefGoogle Scholar
  67. 67.
    Shuqi Huant FZ, Zhao Z, Xie X. Effect of erythropoietin (EPO) on plasticity of nervous synapse in CA1 region of hippocampal of vascular dementia (VaD) rats. Afr J Pharm Pharmacol. 2012;6:1111–7.Google Scholar
  68. 68.
    Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002;8:495–505.PubMedCentralPubMedGoogle Scholar
  69. 69.
    Braunwald E. editor. A Textbook of Cardiovascular Medicine. Rehabilitation of patients with coronary artery disease. Dennis C, author. 4 ed. Philadelphia: Saunders; 1992.Google Scholar
  70. 70.
    Kourea K, Parissis JT, Farmakis D, et al. Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure. Atherosclerosis. 2008;199:215–21.PubMedCrossRefGoogle Scholar
  71. 71.
    Parissis JT, Kourea K, Panou F, et al. Effects of darbepoetin alpha on right and left ventricular systolic and diastolic function in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am Heart J 2008;155:751 e1-7.Google Scholar
  72. 72.
    Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne AS. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003;107:294–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Mille-Hamard L, Billat VL, Henry E, et al. Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study. BMC Med Genom. 2012;5:29.CrossRefGoogle Scholar
  74. 74.
    Cohen RS, Karlin P, Yushak M, Mancini D, Maurer MS. The effect of erythropoietin on exercise capacity, left ventricular remodeling, pressure-volume relationships, and quality of life in older patients with anemia and heart failure with preserved ejection fraction. Congest Heart Fail. 2010;16:96–103.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Palazzuoli A, Silverberg D, Iovine F, et al. Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. Am Heart J 2006;152:1096 e9-15.Google Scholar
  76. 76.
    Ghali JK, Anand IS, Abraham WT, et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation. 2008;117:526–35.PubMedCrossRefGoogle Scholar
  77. 77.
    Kotecha D, Ngo K, Walters JA, Manzano L, Palazzuoli A, Flather MD. Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials. Am Heart J 2011;161:822-31 e2.Google Scholar
  78. 78.
    Jin B, Luo X, Lin H, Li J, Shi H. A meta-analysis of erythropoiesis-stimulating agents in anaemic patients with chronic heart failure. Eur J Heart Fail. 2010;12:249–53.PubMedCrossRefGoogle Scholar
  79. 79.
    Swedberg K, Young JB, Anand IS, et al. RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;28:368(13):1210–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Epoetin alfa (Rx). 2012. Last Accessed on 15 Oct 2012.
  81. 81.
    Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019–32.PubMedCrossRefGoogle Scholar
  82. 82.
    Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–98.PubMedCrossRefGoogle Scholar
  83. 83.
    Epogen medication guide. U.S. Food and Drug Administration, 2012. Last Accessed on 15 Oct 2012.
  84. 84.
    Solomon SD, Uno H, Lewis EF, et al. Erythropoietic response and outcomes in kidney disease and Type 2 diabetes. N Engl J Med. 2010;363:1146–55.PubMedCrossRefGoogle Scholar
  85. 85.
    Szczech LA, Barnhart HX, Inrig JK, et al. Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int. 2008;74:791–8.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Fishbane S, Miyawaki N. Anemia treatment in chronic kidney disease accompanied by diabetes mellitus or congestive heart failure. Kidney Int. 2010;77:175–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Szczech LA, Barnhart HX, Sapp S, et al. A secondary analysis of the CHOIR trial shows that comorbid conditions differentially affect outcomes during anemia treatment. Kidney Int. 2010;77:239–46.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Cleland JG, Sullivan JT, Ball S, et al. Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation. J Cardiovasc Pharmacol. 2005;46:155–61.PubMedCrossRefGoogle Scholar
  89. 89.
    Palazzuoli A, Silverberg DS, Iovine F, et al. Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. Am Heart J 2007;154:645 e9-15.Google Scholar
  90. 90.
    Ponikowski P, Anker SD, Szachniewicz J, et al. Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2007;49:753–62.PubMedCrossRefGoogle Scholar
  91. 91.
    Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 2001;37:1775–80.PubMedCrossRefGoogle Scholar
  92. 92.
    Brines M, Cerami A. Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise. Kidney Int. 2006;70:246–50.PubMedCrossRefGoogle Scholar
  93. 93.
    Ogino A, Takemura G, Kawasaki M, et al. Erythropoietin receptor signaling mitigates renal dysfunction-associated heart failure by mechanisms unrelated to relief of anemia. J Am Coll Cardiol. 2010;56:1949–58.PubMedCrossRefGoogle Scholar
  94. 94.
    De Boer RA, Pinto YM, Van Veldhuisen DJ. The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities. Microcirculation. 2003;10:113–26.PubMedCrossRefGoogle Scholar
  95. 95.
    Fiordaliso F, Chimenti S, Staszewsky L, et al. A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2005;102:2046–51.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Pablos-Mendez A, Barr RG, Shea S. Run-in periods in randomized trials: implications for the application of results in clinical practice. JAMA. 1998;279:222–5.PubMedCrossRefGoogle Scholar
  97. 97.
    Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure. Circulation. 2003;107:226–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Abramov D, Cohen RS, Katz SD, Mancini D, Maurer MS. Comparison of blood volume characteristics in anemic patients with low versus preserved left ventricular ejection fractions. Am J Cardiol. 2008;102:1069–72.PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Mathew S. Maurer ST, Bibhas Chakroborty, Stephen Helmke and Donna Mancini. Treating Anemia in Older Adults with Heart Failure with a Preserved Ejection Fraction (HFPEF) with Epoetin Alfa: Single Blind Randomized Clinical Trial of Safety and Efficacy. Circulation 2012;Heart Failure.Google Scholar
  100. 100.
    Altincatal A, Macarthur RB, Teruya S, Helmke S, Maurer MS. A Dosing Algorithm for Erythropoietin Alpha in Older Adults with Heart Failure and a Preserved Ejection Fraction. Cardiovascular therapeutics 2011.Google Scholar
  101. 101.
    Cosyns B, Velez-Roa S, Droogmans S, Pierard LA, Lancellotti P. Effects of eythropoietin administration on mitral regurgitation and left ventricular remodeling in heart failure patients. Int J Cardiol. 2010;138:306–7.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.University at Buffalo School of MedicineStaten IslandUSA
  2. 2.Department of MedicineColumbia University Medical CenterNew YorkUSA

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