Nadia Kashif, Muhammad Tariq Masood, Jawad Ahmed, Muhammad Hafizullah, Abid Sohail Taj, Adnan Gul, Zahid Aslam Awan


Introduction: Heart Failure is a common problem and major cause of morbidity, mortality and impaired quality of life. Deficiency of iron is common in heart failure patients but the optimum diagnostic tests for detection of iron deficiency and treatment options to replace iron have not been fully characterized. This study was performed to determine whether intravenous iron therapy would improve the symptoms of iron deficient chronic heart failure patients.

Materials & Methods: This was a cross sectional descriptive study in which 96 patients with symptomatic cardiac failure NYHA class II and III were selected from selected tertiary care hospitals of Peshawar, KP, through convenience sampling. Serum ferritin, serum BNP, echocardiography and 6 Minutes’ Walk tests were conducted on all patients, and 38 patients with iron deficiency (Serum Ferritin<100µg/ml) were identified. Intravenous iron was administered to the iron deficient patients weekly for 6 weeks and patients were reassessed through repeat investigations to determine the efficacy of intravenous iron administration in chronic heart failure patients.

Results: High compliance of patients with intravenous iron administration was observed (87%) with symptomatic, biochemical and physical evidence of improvement. After 6 weeks of treatment, reanalysis of these patients indicated significant improvements in Serum Ferritin levels (p<0.001), Serum BNP levels (p=0.002), Echocardiographic findings (p=0.013), 6 Minutes’ Walk test (p < 0.001) and NYHA class shift in 76% of patients (p<0.001).

Conclusions: Parenteral iron administration is an effective modality in managing patients of NYHS class II and III cardiac failure patients.

Keywords: Heart Failure, Anemia, Iron Deficiency, Brain Natriuretic Peptide, Ferritin. 

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Rouault TA, Tong WH. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol. 2005;6:345-51.

Naito Y, Tsujino T, Matsumoto M, Sakoda T, Ohyanagi M, Masuyama T. Adaptive response of the heart to long-term anemia induced by iron deficiency. Am J Physiol Heart Circ Physiol. 2009;296:H585-H593.

Dong F, Zhang X, Culver B, Chew HG Jr, Kelley RO, Ren J. Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration. Clin Sci. 2005;109:277-86.

Opasich C, Cazzola M, Scelsi L, De Feo S, Bosimini E, Lagioia R, 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.

Hower V, Mendes P, Torti FM, Laubenbacher R, Akman S, Shulaev V, et al. A general map of iron metabolism and tissue-specific sub networks. Mol Biosyst. 2009;5:422-43.

Fairbanks V, Beutler E. Iron deficiency. In: Beutler E (ed.), Williams Hematology. 6th ed. New York: McGraw-Hill; 2001. p. 295-304 and p. 447-50.

Dunn LL, Rahmanto YS, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol. 2007;17:93-100.

Cairo G, Bernuzzi F, Recalcati S. A precious metal: iron, an essential nutrient for all cells. Genes Nutr. 2006;1:25-39.

Carrondo MA. Ferritins, iron uptake and storage from the bacterioferritin viewpoint. EMBO J. 2003;22:1959-68.

Elliott J, Mishler D, Agarwal R. Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis. 2009;16:94-100.

Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2009;81:412-9.

de Silva R1, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, et al. Anemia, renal function, and their interaction in patients with chronic heart failure. Am J Cardiol. 2006:98:391-8.

Jankowska EA1, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspective Eur Heart J. 2013;34:816-26.

Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 2013;165:575-82.

Okonko DO, Mandal AKJ, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relations to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011;58:1241-51.

Kasner M, Aleksandrov AS, Westermann D, Lassner D, Gross M, von Haehling S, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol. 2013;168:4652-7.

Jankowska EA, Kasztura M, Sokolski M, Bronisz M, Nawrocka S, Oles´kowska-Florek W, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J. 2014 Sep 21;35(36):2468-76.

Van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC. Anemia and iron deficiency in heart failure: mechanisms and theraputic approaches. Nature Rev Cardiol. 2011;8:485-93.

Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J Card Fail. 2011;17:899-906.

Anvi T, Leibovici L, Gafter-Gvili A. Iron supplementation for the treatment of chronic heart failure and iron deficiency: systematic review and meta-analysis. Eur J Heart Fail. 2012;14:423-9.

Schmaier AH, Petruzzelli LM. Hematology for Medical Students. Lippincott Williams & Wilkins: Philadelphia. PA, 2003. pp. 35-8.

Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131:568S–579S.

Barron BA, Hoyer JD, Tefferi A. A bone marrow report of absent stainable iron is not diagnostic of iron deficiency. Ann Hematol. 2001;80:166-9.

Anderson GJ, Frazer DM, McLaren GD. Iron absorption and metabolism. Curr Opin Gastroenterol. 2009; 25:129-35.

Beard J. Iron status of free-living elderly individuals. Am J Clin Nutr. 2001;73:503–4.

Lopez A, Cacoub P, Macdougall IC, Peyrin‐Biroulet L. Iron deficiency anemia. Lancet. 2016;387:907-16.

Camaschella C. Iron‐deficiency anemia. N Engl J Med. 2015;372:1832-43.

Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271-6.

Ludwiczek S, Aigner E, Theurl I, Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood. 2003;101:4148–54.

Nemeth E1, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–3.

Kraml PJ, Klein RL, Huang Y, Nareika A, Lopes- Virella MF. Iron loading increases cholesterol accumulation and macrophage scavenger receptor I expression in THP-1 mononuclear phagocytes. Metabolism. 2005;54:453–9.

Tang YD, Katz SD. Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation. 2006;113:2454–61.

Weiss G, Goodenough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011–23.

Ingle L, Rigby AS, Carrol S, Butterly R, King RF, Cooke CB, Cleland JG, Clark AL. Prognostic value of the 6 min walk test and self-perceived symptom severity in older patients with chronic heart failure. Eur Heart J. 2007;28:560-9.

Fang J, Mensah GA, Croft JB, Keenan NL. Heart failure-related hospitalization in the U.S., 1979 to 2004. J Am Coll Cardiol. 2008;52:428-34.

Shimizu H, Aono K, Masuta K, Asada H, Misaki A, Teraoka H. Degradation of human brain natriureteric Peptide (BNP) by contact activation of blood coagulation system. Clinica Chimica Acta. 2001;305(1):181-6.

Anand IS. Pathophysiology of anemia in heart failure. Heart Fail Clin. 2010;6:279-88.

Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. (for the FAIR-HF Trial Investigators). Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436-48.

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.

Aessopos A, Deftereos S, Farmakis D, Corovesis C, Tassiopoulos S, Tsironi M, et al. Cardiovascular adaptation to chronic anemia in the elderly: an echocardiographic study. Clin Invest Med. 2004;27:265-73.


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