cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-2113Research ArticleОБЗОРЫREVIEWSАнемия и хроническая сердечная недостаточностьAnaemia and chronic heart failureКазанцеваТ. А.KazantsevaT. A.

аспирант кафедры факультетской терапии

kazanchikmed@mail.ruРаджанРаджешRadjanRadjesh

аспирант кафедры пропедевтики внутренних болезней

ЕфремовцеваМ. А.EfremovtsevaM. A.

доцент кафедры пропедевтики внутренних болезней

АлександрияЛ Г.AlexandriyaL. G.

доцент кафедры факультетской терапии

КобалаваЖ. Д.KobalavaZh. D.

зав.кафедрой пропедевтики внутренних болезней

МоисеевВ. С.MoiseevV. S.

зав.кафедрой факультетской терапии

Российский университет дружбы народов. МоскваRussian University of People’s Friendship. Moscow20102008201094116123Copyright © Казанцева Т.А., Раджан Р., Ефремовцева М.А., Александрия Л.Г., Кобалава Ж.Д., Моисеев В.С., 20102010Казанцева Т.А., Раджан Р., Ефремовцева М.А., Александрия Л.Г., Кобалава Ж.Д., Моисеев В.С.Kazantseva T.A., Radjan R., Efremovtseva M.A., Alexandriya L.G., Kobalava Z.D., Moiseev V.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2113

В настоящее время уделяют большое внимание сочетанию хронической сердечной недостаточности (ХСН) с анемией, которая ухудшает течение СН и неблагоприятно влияет на прогноз. Основным звеном в развитии анемии при ХСН является абсолютная или относительная недостаточность эритропоэтина, обусловленная влиянием провоспалительных цитокинов, а также почечная дисфункция. Работы последних лет показали, что коррекция даже умеренной анемии при ХСН повышает толерантность к физическим нагрузкам, снижает функциональный класс ХСН (NYHA), улучшает качество жизни, структурнофункциональные показатели сердца, уменьшает потребность в диуретиках и числе госпитализаций. Однако отсутствуют данные о влиянии коррекции анемии на долгосрочную выживаемость пациентов, а также уровне гемоглобина, при котором следует начинать коррекцию анемии, и целевых значениях гемоглобина, безопасных для каждого пациента.

Currently, one of the important clinical issues is the combination of chronic heart failure (CHF) and anaemia, which aggravates CHF course and prognosis. The main pathogenetic mechanism of anaemia development in CHF is absolute or relative erythropoietin deficit, due to pro-inflammatory cytokine effects, and renal dysfunction. The recent studies have demonstrated that correcting even moderate anaemia in CHF results in increased exercise tolerance, reduced NYHA functional class, improved quality of life, cardiac morphology and function, decreased need for diuretics, and reduced hospitalization incidence. However, there are no available data on anaemia correction effects on long-term survival, as well as on haemoglobin levels needed to start the anaemia treatment, or safe target levels of haemoglobin.

анемияхроническая сердечная недостаточностьхроническая болезнь почекжелезодефицитная анемияэритропоэтинanaemiachronic heart failurechronic kidney diseaseiron deficiency anaemiaerythropoietinReferencesМсМurray JJ, Steward J. Epidemiolodgy, aetiolodgy, and prognosis of heart failure. Heart 2000; 83: 596-602.МсМurray JJ, Steward J. Epidemiolodgy, aetiolodgy, and prognosis of heart failure. Heart 2000; 83: 596-602.Rickenbacher P. Herzinsuffizienz: Epidemiologie, Patophysiologie. Swiss Med Forum 2001; 1/2: 4-9.Rickenbacher P. Herzinsuffizienz: Epidemiologie, Patophysiologie. Swiss Med Forum 2001; 1/2: 4-9.Арутюнов Г. П., Кафарская Л. И., Савелов Н. А и др. Хроническая сердечная недостаточность: структурные и микробиологические изменения в толстой кишке. Тер архив 2007; 2: 31-7.Арутюнов Г. П., Кафарская Л. И., Савелов Н. А и др. Хроническая сердечная недостаточность: структурные и микробиологические изменения в толстой кишке. Тер архив 2007; 2: 31-7.Komajda M. Prevalence of anemia in patients with chronic heart failure and their clinical characteristics. J Card Fail 2004; 10: S1-4.Komajda M. Prevalence of anemia in patients with chronic heart failure and their clinical characteristics. J Card Fail 2004; 10: S1-4.Anand IS. Pathogenesis of anemia in cardiorenal disease. Rev Cardiovasc Med 2005; 6(Suppl 3): S13-21.Anand IS. Pathogenesis of anemia in cardiorenal disease. Rev Cardiovasc Med 2005; 6(Suppl 3): S13-21.Tang Y-D, Katz SD. The prevalence of anemia in chronic heart failure and its impact on clinical outcomes. Heart Fail Rev 2008; 13: 387-92.Tang Y-D, Katz SD. The prevalence of anemia in chronic heart failure and its impact on clinical outcomes. Heart Fail Rev 2008; 13: 387-92.Tang Y-D, Katz SD. Аnemia in chronic heart failure: prevalence, etiologie, clinical correlates, and treatment optiones. Circulation 2006; 113: 2454-61.Tang Y-D, Katz SD. Аnemia in chronic heart failure: prevalence, etiologie, clinical correlates, and treatment optiones. Circulation 2006; 113: 2454-61.Dallman PR. Iron Nutrition in Health and Disease. Eastleigh, UK: John Libbey & Co., 1996.Dallman PR. Iron Nutrition in Health and Disease. Eastleigh, UK: John Libbey & Co., 1996.Felker GM, Gattis WA, Leimberger JD, et al. Usefulness of anemia as a predictor of death and rehospitalizacion in patients with decompensated heart failure. Am J Cardiol 2003; 92: 625-8.Felker GM, Gattis WA, Leimberger JD, et al. Usefulness of anemia as a predictor of death and rehospitalizacion in patients with decompensated heart failure. Am J Cardiol 2003; 92: 625-8.Go AS, Yang J, Ackerson LM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalizacion in adults with chronic heart failure. Circulation 2006; 113: 2713-23.Go AS, Yang J, Ackerson LM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalizacion in adults with chronic heart failure. Circulation 2006; 113: 2713-23.Ishani A, Weinhandl E, Zhao Z, et al. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. JACC 2005; 45: 391-9.Ishani A, Weinhandl E, Zhao Z, et al. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. JACC 2005; 45: 391-9.Anand IS, Kuskowski MA, Rector TS, et al. Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 2005; 112: 1121-7.Anand IS, Kuskowski MA, Rector TS, et al. Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 2005; 112: 1121-7.Komajda M, Anker SD, Charlesworth A, et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 2006; 27: 1440-6.Komajda M, Anker SD, Charlesworth A, et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 2006; 27: 1440-6.Nair D, Shlipak MG, Angeja B, et al. Association of anemia with diastolic dysfunction among patients with coronary artery disease in the Heart and Soul Study. Am J Cardiol 2005; 95: 332-6.Nair D, Shlipak MG, Angeja B, et al. Association of anemia with diastolic dysfunction among patients with coronary artery disease in the Heart and Soul Study. Am J Cardiol 2005; 95: 332-6.Felker GM, Shaw LK, Stough WG, O’Connor CM. Anemia in patients with heart failure and preserved systolic function. Am Heart J 2006; 151: 457-62.Felker GM, Shaw LK, Stough WG, O’Connor CM. Anemia in patients with heart failure and preserved systolic function. Am Heart J 2006; 151: 457-62.Berry C, Norrie J, Hogg K, et al. The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 2006; 151: 1313-21.Berry C, Norrie J, Hogg K, et al. The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 2006; 151: 1313-21.O’Meara E, Clayton T, McEntegart MB, et al. Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation 2006; 113: 986-94.O’Meara E, Clayton T, McEntegart MB, et al. Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation 2006; 113: 986-94.Anand IS, Rector T, Deswal A, et al. Relationship between proinflammatory cytokines and anemia in heart failure. Eur Heart J 2006; 27 (Suppl 1): 485.Anand IS, Rector T, Deswal A, et al. Relationship between proinflammatory cytokines and anemia in heart failure. Eur Heart J 2006; 27 (Suppl 1): 485.Opasich C, Cazzola M, Scelsi L, et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005; 26: 2232-7.Opasich C, Cazzola M, Scelsi L, et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005; 26: 2232-7.Anand I, McMurray JJ, Whitmore J, et al. Anemia and its relationship to clinical outcome in heart failure. Circulation 2004; 110: 149-54.Anand I, McMurray JJ, Whitmore J, et al. Anemia and its relationship to clinical outcome in heart failure. Circulation 2004; 110: 149-54.Al-Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. JACC 2001; 38: 955-62.Al-Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. JACC 2001; 38: 955-62.Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. JACC 2002; 39: 1780-6.Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. JACC 2002; 39: 1780-6.Ghali JK, Anand IS, Abraham WT, et al. Randomized doubleblind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circilation 2008; 117: 526-35.Ghali JK, Anand IS, Abraham WT, et al. Randomized doubleblind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circilation 2008; 117: 526-35.Sharma R, Francis DP, Pitt B, et al. Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J 2004; 25: 1021-8.Sharma R, Francis DP, Pitt B, et al. Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J 2004; 25: 1021-8.Datta BN, Silver MD. Cardiomegaly in chronic anemia in rats and man experimental study including ultrastructural, histometric, and stereologic observations. Lab Invest 1975; 32: 503-14.Datta BN, Silver MD. Cardiomegaly in chronic anemia in rats and man experimental study including ultrastructural, histometric, and stereologic observations. Lab Invest 1975; 32: 503-14.Olivetti G, Quaini F, Lagrasta C et al. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia- induced cardiac hypertrophy in rats. Am J Pathol 1992; 141: 227-39.Olivetti G, Quaini F, Lagrasta C et al. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia- induced cardiac hypertrophy in rats. Am J Pathol 1992; 141: 227-39.Levin A. The treatment of anemia in chronic kidney disease understandings in 2006. Curr Opin Nephrol Hypertens 2007; 16: 267-71.Levin A. The treatment of anemia in chronic kidney disease understandings in 2006. Curr Opin Nephrol Hypertens 2007; 16: 267-71.Collins AJ. The hemoglobin link to adverse outcomes. Adv Stud Med 2003; 3: S194-7.Collins AJ. The hemoglobin link to adverse outcomes. Adv Stud Med 2003; 3: S194-7.National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis 2002; 39(Suppl.1): S17-31.National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis 2002; 39(Suppl.1): S17-31.Metivier F, Marchais SJ, Guerin AP, et al. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol. Dial Transplant 2000; 15(Suppl. 3): 14-8.Metivier F, Marchais SJ, Guerin AP, et al. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol. Dial Transplant 2000; 15(Suppl. 3): 14-8.Физиология человека. Под ред. Р. Шмидта и Г. Тевса. В 3 томах. М.: Мир 1996; 2: 313 с.Физиология человека. Под ред. Р. Шмидта и Г. Тевса. В 3 томах. М.: Мир 1996; 2: 313 с.Takenaga K, Fukuma N, Seino Y, Takano T. A 69-year-old woman with congestive heart failure caused by myocardial ischemia and severe anemia. J Cardiology 2000; 36(3): 197-9.Takenaga K, Fukuma N, Seino Y, Takano T. A 69-year-old woman with congestive heart failure caused by myocardial ischemia and severe anemia. J Cardiology 2000; 36(3): 197-9.Davie NJ, Crossno JT, Frid MG, et al. Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: potential contribution of circulating progenitor cells (R1). Am J Physiol Lung Cell Mol Physiology 2003; [E pub a head of print].Davie NJ, Crossno JT, Frid MG, et al. Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: potential contribution of circulating progenitor cells (R1). Am J Physiol Lung Cell Mol Physiology 2003; [E pub a head of print].Bauer C, Kurtz A. Oxygen sensing in the kidney and its relation to erythropoietin production. Annu Rev Physiol 1989; 51: 845-56.Bauer C, Kurtz A. Oxygen sensing in the kidney and its relation to erythropoietin production. Annu Rev Physiol 1989; 51: 845-56.Anand IS, Ferrari R, Kalra GS, et al. Edema of cardiac origin. Studies of body water and sodium, renal function, hemodynamic indexes, and plasma hormones in untreated congestive cardiac failure. Circulation 1989; 80: 299-305.Anand IS, Ferrari R, Kalra GS, et al. Edema of cardiac origin. Studies of body water and sodium, renal function, hemodynamic indexes, and plasma hormones in untreated congestive cardiac failure. Circulation 1989; 80: 299-305.McClellan WM, Flanders WD, Langston RD, et al. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002;13:1928-36.McClellan WM, Flanders WD, Langston RD, et al. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002;13:1928-36.Volpe M, Tritto C, Testa U et al. Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles. Am J Cardiol 1994; 74: 468-73.Volpe M, Tritto C, Testa U et al. Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles. Am J Cardiol 1994; 74: 468-73.van der Meer P, Voors AA, Lipsic E, et al. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. JACC 2004; 44: 63-7.van der Meer P, Voors AA, Lipsic E, et al. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. JACC 2004; 44: 63-7.Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12,065 patients with new-onset heart failure. Circulation 2003; 107: 223-5.Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12,065 patients with new-onset heart failure. Circulation 2003; 107: 223-5.Mrug M, Stopka T, Julian BA, et al. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997; 100: 2310-4.Mrug M, Stopka T, Julian BA, et al. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997; 100: 2310-4.Albitar S, Genin R, Fen-Chong M, et al. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant 1998; 13: 1206-10.Albitar S, Genin R, Fen-Chong M, et al. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant 1998; 13: 1206-10.van der Meer P, Lipsic E, Westenbrink BD, et al. Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation 2005; 112: 1743-7.van der Meer P, Lipsic E, Westenbrink BD, et al. Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation 2005; 112: 1743-7.Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997; 18: 208-25.Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997; 18: 208-25.Bolger AP, Bartlett FR, Penston HS, et al. Intravenous iron alone the treatment of anemia in patients with chronic heart failure. JACC 2006; 48: 1225-7.Bolger AP, Bartlett FR, Penston HS, et al. Intravenous iron alone the treatment of anemia in patients with chronic heart failure. JACC 2006; 48: 1225-7.Weiss G, Goodnough LT. Anemia of chronic disease. N Engl JMed 2005; 352: 1011-23.Weiss G, Goodnough LT. Anemia of chronic disease. N Engl JMed 2005; 352: 1011-23.Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001; 103: 2055-9.Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001; 103: 2055-9.Westenbrink BD, Visser FW, Voors AA, et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J 2007; 28: 166-71.Westenbrink BD, Visser FW, Voors AA, et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J 2007; 28: 166-71.Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure. Circulation 2003; 107: 226-9.Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure. Circulation 2003; 107: 226-9.Witte KK, Desilva R, Chattopadhyay S, et al. Are hematinic deficiencies the cause of anemia in chronic heart failure? Am Heart J 2004; 147: 924-30.Witte KK, Desilva R, Chattopadhyay S, et al. Are hematinic deficiencies the cause of anemia in chronic heart failure? Am Heart J 2004; 147: 924-30.Cromie N, Lee C, Struthers AD. Anaemia in chronic heart failure: what is its frequency in the UK and its underlying causes? Heart 2002; 87: 377-8.Cromie N, Lee C, Struthers AD. Anaemia in chronic heart failure: what is its frequency in the UK and its underlying causes? Heart 2002; 87: 377-8.Аstor BC, Muntner P, Levin A, et al. Association of kidney function with anemia. Arch Intern Med 2002; 162: 1401-8.Аstor BC, Muntner P, Levin A, et al. Association of kidney function with anemia. Arch Intern Med 2002; 162: 1401-8.de Silva R, Rigby AS, Witte KK, et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006; 98: 391-8.de Silva R, Rigby AS, Witte KK, et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006; 98: 391-8.Foley RN, Parfrey PS, Harnelt JD, et al. The impact of anemia on eardiomyopathy, morbidity, and mortality in end-stage renal disease Am J Kidney Dis 1996; 28: 53-61.Foley RN, Parfrey PS, Harnelt JD, et al. The impact of anemia on eardiomyopathy, morbidity, and mortality in end-stage renal disease Am J Kidney Dis 1996; 28: 53-61.Rigatto C, Parfrey P. Foley R, et al. Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. Am Sac Nephrol 2002; 13: 1084-90.Rigatto C, Parfrey P. Foley R, et al. Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. Am Sac Nephrol 2002; 13: 1084-90.Anand IS Anemia and Chronic Heart Failure. Implications and Treatment Options. JACC 2008; 52(7): 501-11.Anand IS Anemia and Chronic Heart Failure. Implications and Treatment Options. JACC 2008; 52(7): 501-11.Demetri GD. Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy. Br J Cancer 2001; 84(Suppl 1): 31-7.Demetri GD. Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy. Br J Cancer 2001; 84(Suppl 1): 31-7.Mancini DM, Katz SD, Lang CC, et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003; 107: 294-9.Mancini DM, Katz SD, Lang CC, et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003; 107: 294-9.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: 645e9-15.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: 645e9-15.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. JACC 2007; 49: 753-62.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. JACC 2007; 49: 753-62.van Veldhuisen DJ, Dickstein K, Cohen-Solal A, et al. Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia. Eur Heart J 2007; 28: 2208-16.van Veldhuisen DJ, Dickstein K, Cohen-Solal A, et al. Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia. Eur Heart J 2007; 28: 2208-16.Ghali JK, Anand IS, Abraham WT, et al. Randomized doubleblind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 2008; 117: 526-35.Ghali JK, Anand IS, Abraham WT, et al. Randomized doubleblind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 2008; 117: 526-35.Silverberg DS. Outcomes of anaemia management in renal insufficiency and cardiac disease. Nephrol Dial Transplant 2003; 18 (Suppl 2): ii7-12.Silverberg DS. Outcomes of anaemia management in renal insufficiency and cardiac disease. Nephrol Dial Transplant 2003; 18 (Suppl 2): ii7-12.Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. JACC 2000; 35: 1737-44.Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. JACC 2000; 35: 1737-44.Pfeffer MA, Burdmann EA, Chao-Yin Chen, et al. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease, N Engl J Med 2009; 361: 2019-32.Pfeffer MA, Burdmann EA, Chao-Yin Chen, et al. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease, N Engl J Med 2009; 361: 2019-32.Fishbane S, Ragolia L, Palaia T, et al. Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells. Kidney Int 2004; 65: 452-8.Fishbane S, Ragolia L, Palaia T, et al. Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells. Kidney Int 2004; 65: 452-8.Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071-84.Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071-84.Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl JMed 2006; 355: 2085-98.Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl JMed 2006; 355: 2085-98.Dunn LL, Rahmanto YS, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol 2007; 17: 93-100.Dunn LL, Rahmanto YS, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol 2007; 17: 93-100.Dong F, Zhang X, Culver B, et al. Ren Dietary iron de ciency induces ventricular dilation, mitochondri ultrastructural aberrations and cytochrome c release: involvement nitric oxide synthase and protein tyrosine nitration. Clin Sci (Lon 2005; 109: 277-86.Dong F, Zhang X, Culver B, et al. Ren Dietary iron de ciency induces ventricular dilation, mitochondri ultrastructural aberrations and cytochrome c release: involvement nitric oxide synthase and protein tyrosine nitration. Clin Sci (Lon 2005; 109: 277-86.Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iro reduces NT-pro-brain natriuretic peptide in anemic patients wi chronic heart failure and renal insuf ciency. JACC 2007; 50: 1657-65.Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iro reduces NT-pro-brain natriuretic peptide in anemic patients wi chronic heart failure and renal insuf ciency. JACC 2007; 50: 1657-65.Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intraveno iron sucrose on exercise tolerance in anemic and nonanemic patien with symptomatic chronic heart failure and iron de ciency FERRIC HF: a randomized, controlled, observer-blinded trial. JACC 2008; 51: 103-12.Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intraveno iron sucrose on exercise tolerance in anemic and nonanemic patien with symptomatic chronic heart failure and iron de ciency FERRIC HF: a randomized, controlled, observer-blinded trial. JACC 2008; 51: 103-12.Beck-da-Silva L, Luı ´s Eduardo Rohde L, Pereira-Barretto AC, et Rationale and Design of the IRON-HF Study: A Randomized Tri to Assess the Effects of Iron Supplementation in Heart Failu Patients With Anemia. J Card Fail 2007; 13.Beck-da-Silva L, Luı ´s Eduardo Rohde L, Pereira-Barretto AC, et Rationale and Design of the IRON-HF Study: A Randomized Tri to Assess the Effects of Iron Supplementation in Heart Failu Patients With Anemia. J Card Fail 2007; 13.Charytan C, Schwenk MH, Al-Saloum MM, Spinowitz BS. Safety of iron sucrose in hemodialisis patients intolerant to other parenteral iron product. Nephron Clin Pract 2004; 96(2): 63-6.Charytan C, Schwenk MH, Al-Saloum MM, Spinowitz BS. Safety of iron sucrose in hemodialisis patients intolerant to other parenteral iron product. Nephron Clin Pract 2004; 96(2): 63-6.Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2001; 345: 1230-6.Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2001; 345: 1230-6.Cavill I. Intravenosus iron as adjuvant therapy: a two-edged sword? Nephrool Dial Transplant 2003; 18 (Suppl 8): viii24-8.Cavill I. Intravenosus iron as adjuvant therapy: a two-edged sword? Nephrool Dial Transplant 2003; 18 (Suppl 8): viii24-8.Dickstein K, Cohen-Solal A Filippatos G, et al. Guidelines the diagnosis and treatment of agute and chronic heart failure 2008. Eur Heart J 2008; 29: 2388-442.Dickstein K, Cohen-Solal A Filippatos G, et al. Guidelines the diagnosis and treatment of agute and chronic heart failure 2008. Eur Heart J 2008; 29: 2388-442.

The authors declare that there are no conflicts of interest present.