Letter to the Editor
Iron metabolism in heart failure: Mechanisms and therapeutic approaches
Metabolismo do ferro na insuficiência cardíaca: mecanismos e abordagens terapêuticas
Carla Miranda
, Fernando Antônio Botoni, Manoel Ótavio da Costa Rocha
Corresponding author
Universidade Federal de Minas Gerais, Escola de Medicina, UFMG, Belo Horizonte, MG.Brazil
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class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Iron metabolism in heart failure: Mechanisms and therapeutic approaches" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "635" "paginaFinal" => "636" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Carla Miranda, Fernando Antônio Botoni, Manoel Ótavio da Costa Rocha" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Carla" "apellidos" => "Miranda" "email" => array:1 [ 0 => "carlamedicina@ufmg.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Fernando Antônio" "apellidos" => "Botoni" ] 2 => array:2 [ "nombre" => "Manoel Ótavio" "apellidos" => "da Costa Rocha" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Universidade Federal de Minas Gerais, Escola de Medicina, UFMG, Belo Horizonte, MG.Brazil" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Metabolismo do ferro na insuficiência cardíaca: mecanismos e abordagens terapêuticas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Anemia is frequent in heart failure (HF) patients, and is considered an independent factor for worse prognosis.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1–3</span></a> However, it is not known whether anemia causes worsening of the disease course or is only a sign of the patient's cardiac and systemic impairment. The definition of anemia according to the World Health Organization has the following criteria: for women, hemoglobin <12 g/dl (7.5 mmol/l) and for men, <13 g/dl (<8.1 mmol/l).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a> However, other criteria exist, and multicenter studies and meta-analyses have demonstrated that anemia is present in 22–37% of patients with HF.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A recent meta-analysis studied anemia and mortality in more than 150<span class="elsevierStyleHsp" style=""></span>000 patients with HF.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> It was observed that mortality in patients with anemia was nearly double that of nonanemic patients. The etiology of anemia in HF has been shown to be multifactorial, and can be caused by increased plasma volume or reduced red cell mass (“true anemia”).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> It is necessary to understand the factors that lead to decrease hemoglobin in patients with HF. Another plausible factor is the activation of pro-inflammatory cytokines (interleukin-6, interleukin-1, interferon-gamma and TNF-alpha),<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> that plays a fundamental role in the inhibition of hematopoiesis, reducing erythropoietin production.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In a paper on renal transplant patients published in a recent issue of the Journal Rev. Port. Cardiol., Nunes et al. found that the levels of antibodies were associated with reduced left ventricular ejection fraction (LVEF). Based on their findings the authors report that inflammatory mediators such as antibodies (IgG and IgM) can be used as a marker of cardiac dysfunction.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a> This, by negative feedback, would lead to the inhibition of iron absorption at the duodenal level. Also, the drugs routinely administered to HF patients, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and carvedilol, have been known to inhibit the production of erythropoietin.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> Our research group performed a random double-blind study in 2007, assessing left ventricular systolic function in patients with chronic Chagas cardiomyopathy before any therapeutic intervention (Botoni et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a>). In preliminary studies as yet to be published, a negative correlation was observed between the serum hemoglobin level and the B-type natriuretic peptide (BNP), confirming a close neurohormonal relationship with the ventricular fuction. Nevertheless, in this study, there was a significant reduction in blood pressure, as well as in serum hemoglobin levels, but without any cases of anemia. This is important, since low hemoglobin levels increase cardiac work as well as the activity of the renin-angiotensin-aldosterone system, leading to increased cardiac remodeling.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Studies have shown the value of administering erythropoietin intravenously in patients with mild to severe congestive HF and in patients with chronic kidney failure. This treatment seems to be an efficient therapy that is largely responsible for improved prognosis as shown by New York Heart Association functional class, LVEF, left ventricular dilation and hypertrophy, BNP, exercise capacity and quality of life. Studies on therapeutic interventions performed in Italy and Greece, published in 2006 and 2008 respectively, show that the administration of erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa in patients with heart failure increase and maintain hemoglobin levels, leading to improvements in physical ability and in quality of life.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> On the other hand, a study on 319 patients randomized to placebo or darbepoetin alfa showed no improvement in exercise capacity, but mortality and hospitalization were low (hazard ratio 0.68, 95% confidence interval 0.43–1.08, p=0.10). However, patients with heart failure and anemia treated with ESAs present significantly increased risk of cardiovascular events, including myocardial infarction and thromboembolic events.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conclusion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Changes in the metabolism of iron and its relation to the inflammatory response appear to exert significant pathogenic role in patients with heart failure.</p><p id="par1025" class="elsevierStylePara elsevierViewall">A better understanding of these changes and interrelationships may lead to the development of alternative treatments for these patients.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conclusion" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0070" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of a citywide sanitation program in Northeast Brazil on intestinal parasites infection in young children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 5 | 10 |
| 2024 October | 25 | 30 | 55 |
| 2024 September | 35 | 22 | 57 |
| 2024 August | 36 | 23 | 59 |
| 2024 July | 34 | 23 | 57 |
| 2024 June | 29 | 20 | 49 |
| 2024 May | 18 | 17 | 35 |
| 2024 April | 22 | 28 | 50 |
| 2024 March | 26 | 27 | 53 |
| 2024 February | 19 | 43 | 62 |
| 2024 January | 13 | 37 | 50 |
| 2023 December | 29 | 22 | 51 |
| 2023 November | 25 | 13 | 38 |
| 2023 October | 21 | 15 | 36 |
| 2023 September | 16 | 21 | 37 |
| 2023 August | 19 | 18 | 37 |
| 2023 July | 13 | 12 | 25 |
| 2023 June | 14 | 12 | 26 |
| 2023 May | 26 | 21 | 47 |
| 2023 April | 10 | 5 | 15 |
| 2023 March | 16 | 16 | 32 |
| 2023 February | 20 | 15 | 35 |
| 2023 January | 10 | 12 | 22 |
| 2022 December | 23 | 25 | 48 |
| 2022 November | 25 | 19 | 44 |
| 2022 October | 14 | 15 | 29 |
| 2022 September | 20 | 26 | 46 |
| 2022 August | 23 | 34 | 57 |
| 2022 July | 19 | 23 | 42 |
| 2022 June | 14 | 19 | 33 |
| 2022 May | 16 | 31 | 47 |
| 2022 April | 14 | 22 | 36 |
| 2022 March | 21 | 25 | 46 |
| 2022 February | 14 | 21 | 35 |
| 2022 January | 14 | 17 | 31 |
| 2021 December | 14 | 32 | 46 |
| 2021 November | 20 | 43 | 63 |
| 2021 October | 23 | 49 | 72 |
| 2021 September | 16 | 27 | 43 |
| 2021 August | 27 | 32 | 59 |
| 2021 July | 17 | 19 | 36 |
| 2021 June | 9 | 16 | 25 |
| 2021 May | 26 | 38 | 64 |
| 2021 April | 21 | 19 | 40 |
| 2021 March | 50 | 12 | 62 |
| 2021 February | 37 | 13 | 50 |
| 2021 January | 19 | 18 | 37 |
| 2020 December | 31 | 5 | 36 |
| 2020 November | 22 | 10 | 32 |
| 2020 October | 14 | 7 | 21 |
| 2020 September | 41 | 15 | 56 |
| 2020 August | 10 | 5 | 15 |
| 2020 July | 34 | 9 | 43 |
| 2020 June | 17 | 10 | 27 |
| 2020 May | 25 | 3 | 28 |
| 2020 April | 26 | 9 | 35 |
| 2020 March | 22 | 8 | 30 |
| 2020 February | 60 | 42 | 102 |
| 2020 January | 16 | 4 | 20 |
| 2019 December | 26 | 7 | 33 |
| 2019 November | 30 | 5 | 35 |
| 2019 October | 13 | 7 | 20 |
| 2019 September | 23 | 11 | 34 |
| 2019 August | 26 | 5 | 31 |
| 2019 July | 28 | 7 | 35 |
| 2019 June | 25 | 9 | 34 |
| 2019 May | 27 | 12 | 39 |
| 2019 April | 19 | 17 | 36 |
| 2019 March | 43 | 13 | 56 |
| 2019 February | 40 | 10 | 50 |
| 2019 January | 31 | 5 | 36 |
| 2018 December | 32 | 9 | 41 |
| 2018 November | 65 | 11 | 76 |
| 2018 October | 176 | 18 | 194 |
| 2018 September | 58 | 13 | 71 |
| 2018 August | 24 | 6 | 30 |
| 2018 July | 22 | 2 | 24 |
| 2018 June | 40 | 5 | 45 |
| 2018 May | 54 | 3 | 57 |
| 2018 April | 54 | 3 | 57 |
| 2018 March | 51 | 6 | 57 |
| 2018 February | 14 | 4 | 18 |
| 2018 January | 14 | 1 | 15 |
| 2017 December | 33 | 12 | 45 |
| 2017 November | 11 | 13 | 24 |
| 2017 October | 26 | 11 | 37 |
| 2017 September | 21 | 9 | 30 |
| 2017 August | 15 | 9 | 24 |
| 2017 July | 16 | 7 | 23 |
| 2017 June | 23 | 7 | 30 |
| 2017 May | 17 | 10 | 27 |
| 2017 April | 22 | 4 | 26 |
| 2017 March | 22 | 7 | 29 |
| 2017 February | 22 | 2 | 24 |
| 2017 January | 19 | 6 | 25 |
| 2016 December | 24 | 8 | 32 |
| 2016 November | 25 | 4 | 29 |
| 2016 October | 22 | 3 | 25 |
| 2016 September | 21 | 3 | 24 |
| 2016 August | 9 | 1 | 10 |
| 2016 July | 19 | 2 | 21 |
| 2016 June | 15 | 4 | 19 |
| 2016 May | 16 | 6 | 22 |
| 2016 April | 11 | 5 | 16 |
| 2016 March | 14 | 9 | 23 |
| 2016 February | 21 | 16 | 37 |
| 2016 January | 17 | 17 | 34 |
| 2015 December | 12 | 9 | 21 |
| 2015 November | 26 | 11 | 37 |
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