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      Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

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          Abstract

          This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work-up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double-blind, placebo-controlled FAIR-HF and CONFIRM-HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.

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          Most cited references88

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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            Iron biology in immune function, muscle metabolism and neuronal functioning.

            J Beard (2001)
            The estimated prevalence of iron deficiency in the world suggests that there should be widespread negative consequences of this nutrient deficiency in both developed and developing countries. In considering the reality of these estimates, the Belmont Conference seeks to reconsider the accepted relationships of iron status to physiological, biochemical and neurological outcomes. This review focuses on the biological processes that we believe are the basis for alterations in the immune system, neural systems, and energy metabolism and exercise. The strength of evidence is considered in each of the domains and the large gaps in knowledge of basic biology or iron-dependent processes are identified. Iron is both an essential nutrient and a potential toxicant to cells; it requires a highly sophisticated and complex set of regulatory approaches to meet the demands of cells as well as prevent excess accumulation. It is hoped that this review of the more basic aspects of the biology of iron will set the stage for subsequent in-depth reviews of the relationship of iron to morbidity, mortality and functioning of iron-deficient individuals and populations.
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              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.

              We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency. Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance. We randomized 35 patients with CHF (age 64 +/- 13 years, peak oxygen consumption [pVO2] 14.0 +/- 2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/ml, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dl [anemic group] vs. 12.5 to 14.5 g/dl [nonanemic group]). The observer-blinded primary end point was the change in absolute pVO2. The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p < 0.0001), 0.1 (-0.8 to 0.9) g/dl for hemoglobin (p = 0.9), 96 (-12 to 205) ml/min for absolute pVO2 (p = 0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg (p = 0.01), 60 (-6 to 126) s for treadmill exercise duration (p = 0.08), -0.6 (-0.9 to -0.2) for New York Heart Association (NYHA) functional class (p = 0.007), and 1.7 (0.7 to 2.6) for patient global assessment (p = 0.002). In anemic patients (n = 18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute pVO2 (p = 0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p = 0.01). In nonanemic patients, NYHA functional class improved (p = 0.06). Adverse events were similar. Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).
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                Author and article information

                Journal
                Eur J Heart Fail
                Eur. J. Heart Fail
                ejhf
                European Journal of Heart Failure
                John Wiley & Sons, Ltd (Oxford, UK )
                1388-9842
                1879-0844
                March 2015
                30 January 2015
                30 January 2015
                : 17
                : 3
                : 248-262
                Affiliations
                [1 ]Department of Cardiology, King’s College Hospital London, UK
                [2 ]Department of Renal Medicine, King’s College Hospital London, UK
                Author notes
                * Corresponding author: Department of Cardiology, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Tel: +44 203 299 3259, Fax: +44 203 299 3489, Email: theresa.mcdonagh@ 123456kcl.ac.uk
                Article
                10.1002/ejhf.236
                4671256
                25639592
                0af35b03-cfad-4a59-8fd0-afcce37964e6
                © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 24 July 2014
                : 20 October 2014
                : 21 November 2014
                Categories
                Reviews

                Cardiovascular Medicine
                iron deficiency,iron,heart failure,anaemia,intravenous,oral,quality of life
                Cardiovascular Medicine
                iron deficiency, iron, heart failure, anaemia, intravenous, oral, quality of life

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