Approach to anemia in adults with heart failure
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
- Section Editors
- Stephen S Gottlieb, MD
Stephen S Gottlieb, MD
- Section Editor — Heart Failure
- Professor of Medicine
- University of Maryland School of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Anemia is a frequent finding in adults with heart failure (HF), with prevalence varying depending upon the population studied . As an example, in an analysis from the SOLVD trial, 22 percent of patients had a hematocrit ≤39 percent and 4 percent had values below 35 percent . A similar rate of anemia (17 percent) was noted in a population-based cohort of 12,065 patients with newly diagnosed HF . The incidence of anemia appears to increase with worsening functional class (from 9 percent for New York Heart Association class I to 79 percent for class IV in one report) (table 1) .
Evaluation, prognosis and treatment of anemia in patients with HF will be reviewed here . General approaches to anemia in adults and older adults are presented separately. (See "Approach to the adult patient with anemia" and "Anemia in the older adult".)
General considerations — Symptoms related to anemia can result from decreased oxygen delivery to tissues, and, in patients with acute, severe bleeding, the added insult of hypovolemia. Symptoms of anemia such as dyspnea and fatigue may be difficult to distinguish from symptoms of heart failure (HF). (See "Approach to the adult patient with anemia", section on 'Symptoms'.)
Symptoms from reduced oxygen delivery due to anemia generally occur only with severe anemia, but may occur at less severely reduced hemoglobin levels in patients with HF. Since the extraction of oxygen by tissues can increase from 25 to about 60 percent with anemia or hypoperfusion, in individuals with normal hemodynamics, normal oxygen delivery is preserved by extraction alone down to a hemoglobin concentration of about 8 g/dL. The hemodynamic effects of chronic anemia were evaluated in a right heart catheterization study . Normal cardiac hemodynamics were maintained in patients with hemoglobin values as low as 7 g/dL; the cardiac output increased at lower hemoglobin concentrations.
In healthy individuals, acute, isovolemic reduction in the hemoglobin concentration induces a variety of compensatory changes including increases in heart rate, stroke volume, and cardiac index along with enhanced tissue oxygen extraction . The net effect is that oxygen delivery can be maintained at rest at a hemoglobin concentration below 5 g/dL (equivalent to a hematocrit of 15 percent) if intravascular volume is maintained.
- Felker GM, Adams KF Jr, Gattis WA, O'Connor CM. Anemia as a risk factor and therapeutic target in heart failure. J Am Coll Cardiol 2004; 44:959.
- 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. J Am Coll Cardiol 2001; 38:955.
- 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.
- 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. J Am Coll Cardiol 2000; 35:1737.
- Shah R, Agarwal AK. Anemia associated with chronic heart failure: current concepts. Clin Interv Aging 2013; 8:111.
- Brannon ES, Merrill AJ, Warren JV, Stead EA. THE CARDIAC OUTPUT IN PATIENTS WITH CHRONIC ANEMIA AS MEASURED BY THE TECHNIQUE OF RIGHT ATRIAL CATHETERIZATION. J Clin Invest 1945; 24:332.
- Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279:217.
- 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. J Am Coll Cardiol 2002; 39:1780.
- Torre-Amione G, Kapadia S, Benedict C, et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 1996; 27:1201.
- Anand IS. Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 2008; 52:501.
- Nanas JN, Matsouka C, Karageorgopoulos D, et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 2006; 48:2485.
- Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361:2436.
- Toblli JE, Lombraña A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007; 50:1657.
- Jankowska EA, Malyszko J, Ardehali H, et al. Iron status in patients with chronic heart failure. Eur Heart J 2013; 34:827.
- Matsumoto M, Tsujino T, Lee-Kawabata M, et al. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia. Circ J 2010; 74:301.
- Divakaran V, Mehta S, Yao D, et al. Hepcidin in anemia of chronic heart failure. Am J Hematol 2011; 86:107.
- Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure. Circulation 2003; 107:226.
- Adlbrecht C, Kommata S, Hülsmann M, et al. Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body's red cell volume. Eur Heart J 2008; 29:2343.
- Hughes DA, Stuart-Smith SE, Bain BJ. How should stainable iron in bone marrow films be assessed? J Clin Pathol 2004; 57:1038.
- 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. J Am Coll Cardiol 2005; 45:391.
- 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.
- Comín-Colet J, Ruiz S, Cladellas M, et al. A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes. J Card Fail 2009; 15:727.
- Silverberg DS, Wexler D, Iaina A, Schwartz D. The correction of anemia in patients with the combination of chronic kidney disease and congestive heart failure may prevent progression of both conditions. Clin Exp Nephrol 2009; 13:101.
- Pagourelias ED, Koumaras C, Kakafika AI, et al. Cardiorenal anemia syndrome: do erythropoietin and iron therapy have a place in the treatment of heart failure? Angiology 2009; 60:74.
- Usmanov RI, Zueva EB, Silverberg DS, Shaked M. Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency. J Nephrol 2008; 21:236.
- Lu KJ, Kearney LG, Hare DL, et al. Cardiorenal anemia syndrome as a prognosticator for death in heart failure. Am J Cardiol 2013; 111:1187.
- He SW, Wang LX. The impact of anemia on the prognosis of chronic heart failure: a meta-analysis and systemic review. Congest Heart Fail 2009; 15:123.
- Anand I, McMurray JJ, Whitmore J, et al. Anemia and its relationship to clinical outcome in heart failure. Circulation 2004; 110:149.
- Mozaffarian D, Nye R, Levy WC. Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE). J Am Coll Cardiol 2003; 41:1933.
- Kosiborod M, Smith GL, Radford MJ, et al. The prognostic importance of anemia in patients with heart failure. Am J Med 2003; 114:112.
- Felker GM, Gattis WA, Leimberger JD, et al. Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 2003; 92:625.
- 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.
- Maggioni AP, Opasich C, Anand I, et al. Anemia in patients with heart failure: prevalence and prognostic role in a controlled trial and in clinical practice. J Card Fail 2005; 11:91.
- 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.
- Tang WH, Tong W, Jain A, et al. Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J Am Coll Cardiol 2008; 51:569.
- Kosiborod M, Curtis JP, Wang Y, et al. Anemia and outcomes in patients with heart failure: a study from the National Heart Care Project. Arch Intern Med 2005; 165:2237.
- Dunlay SM, Weston SA, Redfield MM, et al. Anemia and heart failure: a community study. Am J Med 2008; 121:726.
- Go AS, Yang J, Ackerson LM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation 2006; 113:2713.
- 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.
- Kalra PR, Collier T, Cowie MR, et al. Haemoglobin concentration and prognosis in new cases of heart failure. Lancet 2003; 362:211.
- 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.
- Chatterjee B, Nydegger UE, Mohacsi P. Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists. Eur J Heart Fail 2000; 2:393.
- Guo L, Wang AH, Sun YL, et al. Serum erythropoietin level predicts the prognosis of chronic heart failure with or without anemia. Exp Ther Med 2013; 6:1327.
- van der Meer P, Voors AA, Lipsic E, et al. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 2004; 44:63.
- Foley RN, Parfrey PS, Harnett JD, et al. The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease. Am J Kidney Dis 1996; 28:53.
- Silberberg JS, Rahal DP, Patton DR, Sniderman AD. Role of anemia in the pathogenesis of left ventricular hypertrophy in end-stage renal disease. Am J Cardiol 1989; 64:222.
- Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol 2011; 58:1241.
- Maeder MT, Khammy O, dos Remedios C, Kaye DM. Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure. J Am Coll Cardiol 2011; 58:474.
- Kansagara D, Dyer E, Englander H, et al. Treatment of anemia in patients with heart disease: a systematic review. Ann Intern Med 2013; 159:746.
- Carson JL, Terrin ML, Noveck H, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011; 365:2453.
- Garty M, Cohen E, Zuchenko A, et al. Blood transfusion for acute decompensated heart failure--friend or foe? Am Heart J 2009; 158:653.
- Kao DP, Kreso E, Fonarow GC, Krantz MJ. Characteristics and outcomes among heart failure patients with anemia and renal insufficiency with and without blood transfusions (public discharge data from California 2000-2006). Am J Cardiol 2011; 107:69.
- Swedberg K, Young JB, Anand IS, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 2013; 368:1210.
- 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.
- Marsden PA. Treatment of anemia in chronic kidney disease--strategies based on evidence. N Engl J Med 2009; 361:2089.
- Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008; 51:103.
- Bolger AP, Bartlett FR, Penston HS, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 2006; 48:1225.
- Jankowska EA, von Haehling S, Anker SD, et al. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J 2013; 34:816.
- Comin-Colet J, Lainscak M, Dickstein K, et al. The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study. Eur Heart J 2013; 34:30.
- Dec GW. Anemia and iron deficiency--new therapeutic targets in heart failure? N Engl J Med 2009; 361:2475.
- Lewis GD, Semigran MJ, Givertz MM, et al. Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction: Design and Rationale for Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure. Circ Heart Fail 2016; 9.
- Qaseem A, Humphrey LL, Fitterman N, et al. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2013; 159:770.
- Clinical presentation
- - General considerations
- - Development of high-output HF
- Initial evaluation
- Potential causes of anemia related to heart failure
- - Increased circulating cytokines and the anemia of inflammation
- - Dilutional anemia
- - Iron deficiency
- - Use of angiotensin converting enzyme inhibitors
- - Renal dysfunction and other contributing factors
- Endogenous erythropoietin
- Changes in hemoglobin
- Low transferrin saturation
- Erythropoiesis stimulating agents
- - Intravenous iron
- - Oral iron
- Society guidelines
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS