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
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Universidade Federal de Minas Gerais, Escola de Medicina, UFMG, Belo Horizonte, MG.Brazil
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=> 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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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 7 | 5 | 12 |
| 2024 Outubro | 33 | 27 | 60 |
| 2024 Setembro | 53 | 23 | 76 |
| 2024 Agosto | 46 | 26 | 72 |
| 2024 Julho | 41 | 31 | 72 |
| 2024 Junho | 37 | 21 | 58 |
| 2024 Maio | 29 | 28 | 57 |
| 2024 Abril | 34 | 24 | 58 |
| 2024 Maro | 42 | 25 | 67 |
| 2024 Fevereiro | 39 | 28 | 67 |
| 2024 Janeiro | 18 | 31 | 49 |
| 2023 Dezembro | 23 | 20 | 43 |
| 2023 Novembro | 33 | 15 | 48 |
| 2023 Outubro | 24 | 16 | 40 |
| 2023 Setembro | 23 | 19 | 42 |
| 2023 Agosto | 23 | 30 | 53 |
| 2023 Julho | 20 | 15 | 35 |
| 2023 Junho | 33 | 13 | 46 |
| 2023 Maio | 32 | 28 | 60 |
| 2023 Abril | 13 | 7 | 20 |
| 2023 Maro | 36 | 26 | 62 |
| 2023 Fevereiro | 26 | 18 | 44 |
| 2023 Janeiro | 11 | 17 | 28 |
| 2022 Dezembro | 28 | 22 | 50 |
| 2022 Novembro | 40 | 25 | 65 |
| 2022 Outubro | 21 | 16 | 37 |
| 2022 Setembro | 19 | 27 | 46 |
| 2022 Agosto | 28 | 30 | 58 |
| 2022 Julho | 28 | 26 | 54 |
| 2022 Junho | 25 | 20 | 45 |
| 2022 Maio | 22 | 25 | 47 |
| 2022 Abril | 29 | 25 | 54 |
| 2022 Maro | 20 | 22 | 42 |
| 2022 Fevereiro | 17 | 17 | 34 |
| 2022 Janeiro | 23 | 22 | 45 |
| 2021 Dezembro | 14 | 30 | 44 |
| 2021 Novembro | 34 | 32 | 66 |
| 2021 Outubro | 24 | 52 | 76 |
| 2021 Setembro | 30 | 30 | 60 |
| 2021 Agosto | 35 | 24 | 59 |
| 2021 Julho | 40 | 29 | 69 |
| 2021 Junho | 27 | 29 | 56 |
| 2021 Maio | 34 | 25 | 59 |
| 2021 Abril | 44 | 44 | 88 |
| 2021 Maro | 61 | 14 | 75 |
| 2021 Fevereiro | 54 | 13 | 67 |
| 2021 Janeiro | 37 | 7 | 44 |
| 2020 Dezembro | 30 | 11 | 41 |
| 2020 Novembro | 27 | 18 | 45 |
| 2020 Outubro | 18 | 5 | 23 |
| 2020 Setembro | 34 | 10 | 44 |
| 2020 Agosto | 18 | 8 | 26 |
| 2020 Julho | 67 | 14 | 81 |
| 2020 Junho | 30 | 7 | 37 |
| 2020 Maio | 27 | 4 | 31 |
| 2020 Abril | 34 | 9 | 43 |
| 2020 Maro | 23 | 7 | 30 |
| 2020 Fevereiro | 42 | 9 | 51 |
| 2020 Janeiro | 28 | 10 | 38 |
| 2019 Dezembro | 22 | 11 | 33 |
| 2019 Novembro | 31 | 8 | 39 |
| 2019 Outubro | 29 | 7 | 36 |
| 2019 Setembro | 22 | 8 | 30 |
| 2019 Agosto | 20 | 9 | 29 |
| 2019 Julho | 38 | 10 | 48 |
| 2019 Junho | 25 | 10 | 35 |
| 2019 Maio | 25 | 9 | 34 |
| 2019 Abril | 15 | 8 | 23 |
| 2019 Maro | 23 | 10 | 33 |
| 2019 Fevereiro | 36 | 15 | 51 |
| 2019 Janeiro | 16 | 4 | 20 |
| 2018 Dezembro | 17 | 8 | 25 |
| 2018 Novembro | 48 | 8 | 56 |
| 2018 Outubro | 78 | 14 | 92 |
| 2018 Setembro | 31 | 9 | 40 |
| 2018 Agosto | 24 | 15 | 39 |
| 2018 Julho | 14 | 5 | 19 |
| 2018 Junho | 31 | 4 | 35 |
| 2018 Maio | 41 | 7 | 48 |
| 2018 Abril | 45 | 4 | 49 |
| 2018 Maro | 35 | 12 | 47 |
| 2018 Fevereiro | 17 | 1 | 18 |
| 2018 Janeiro | 20 | 5 | 25 |
| 2017 Dezembro | 27 | 11 | 38 |
| 2017 Novembro | 23 | 4 | 27 |
| 2017 Outubro | 16 | 11 | 27 |
| 2017 Setembro | 26 | 6 | 32 |
| 2017 Agosto | 23 | 19 | 42 |
| 2017 Julho | 21 | 10 | 31 |
| 2017 Junho | 31 | 10 | 41 |
| 2017 Maio | 22 | 8 | 30 |
| 2017 Abril | 10 | 4 | 14 |
| 2017 Maro | 20 | 1 | 21 |
| 2017 Fevereiro | 19 | 7 | 26 |
| 2017 Janeiro | 16 | 4 | 20 |
| 2016 Dezembro | 17 | 4 | 21 |
| 2016 Novembro | 13 | 3 | 16 |
| 2016 Outubro | 14 | 10 | 24 |
| 2016 Setembro | 14 | 4 | 18 |
| 2016 Agosto | 16 | 2 | 18 |
| 2016 Julho | 9 | 6 | 15 |
| 2016 Junho | 9 | 9 | 18 |
| 2016 Maio | 1 | 0 | 1 |
| 2016 Abril | 5 | 1 | 6 |
| 2016 Maro | 17 | 9 | 26 |
| 2016 Fevereiro | 17 | 18 | 35 |
| 2016 Janeiro | 29 | 12 | 41 |
| 2015 Dezembro | 29 | 12 | 41 |
| 2015 Novembro | 52 | 26 | 78 |
| 2015 Outubro | 73 | 53 | 126 |
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