Brief review
Heart failure in patients with kidney disease and iron deficiency: The role of iron therapy
Insuficiencia cardíaca en la enfermedad renal y déficit de hierro: importancia de la ferroterapia
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"identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Raquel" "apellidos" => "Ojeda López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "José María" "apellidos" => "Portolés Pérez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 3 => array:2 [ "colaborador" => "en representación del Grupo de Anemia de la S.E.N." "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">◊</span>" "identificador" => "fn1" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Clínic, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universitat de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "IDIBAPS, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "REDINREN 016/009/009 ISCiii, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Insuficiencia cardíaca en la enfermedad renal y déficit de hierro: importancia de la ferroterapia" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Anaemia is a common complication in heart failure (HF) patients and is associated with more symptoms, worse functional class, a higher rate of hospitalisation and greater mortality.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">1,2</span></a> In addition, changes in anaemia status during follow-up in patients with HF modify the risk of mortality.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a> The presence of chronic kidney disease (CKD) is also very common in this population, and the prevalence of HF increases as the glomerular filtration rate decreases.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> In addition, anaemia is more prevalent in patients with HF and CKD.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> This complication is therefore emerging as a potentially modifiable and important factor in the treatment of chronic HF.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">1,6</span></a> The presence of CKD or anaemia are associated with increased morbidity and mortality in HF, and the interaction of a decreased glomerular filtration rate and low haemoglobin level on mortality are additional risk factors.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> The causes of anaemia in HF include: iron deficiency, renal dysfunction and neurohormonal activation and the presence of pro-inflammatory cytokines resulting in a deficient production of erythropoietin and impaired utilisation of iron, as well as malnutrition, which is common in these patients; haemodilution also contributes to anaemia.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Treatment of anaemia in patients with HF with erythropoiesis-stimulating agents (ESAs) presented promising results in pilot studies that have not been confirmed in controlled clinical trials. The large clinical trial specifically designed to analyse events and mortality, the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> has not demonstrated benefits in the primary composite outcome of mortality and hospital admission for HF in these patients. In addition, a recent meta-analysis of the treatment of anaemia with an ESA in patients with HF concluded that it improves the symptoms (dyspnoea and quality of life), but it has a neutral effect in terms of mortality or readmission rate, and an increased risk of thromboembolic events.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Therefore, recently the focus has been on iron therapy, as it is well known that iron deficiency has a negative effect that goes beyond the generation of anaemia in HF.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Iron deficiency in heart failure</span><p id="par0020" class="elsevierStylePara elsevierViewall">Clinical guidelines and consensus documents define iron deficiency in patients with HF based on ferritin levels <100<span class="elsevierStyleHsp" style=""></span>μg/l or between 100–300<span class="elsevierStyleHsp" style=""></span>μg/l with transferrin saturation <20%. It is estimated that between 30% and 50% of patients with HF have iron deficiency.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">10,11</span></a> Iron deficiency may cause anaemia, but it also has a direct harmful effect on myocytes.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">10,11</span></a> Both pathophysiological mechanisms explain the relationship between iron deficiency and the risk of morbidity and mortality in HF, which is independent of the haemoglobin level.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">11–13</span></a> These data have positioned iron deficiency as a new therapeutic target for these patients.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">10–13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In fact, in two randomised trials in patients with HF and iron deficiency, intravenous (IV) iron therapy had a beneficial effect.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">14–16</span></a> The study “Ferinject assessment in patients with iron deficiency and chronic heart failure” (FAIR-HF) showed that treatment with ferric carboxymaltose for six months improved quality of life, functional class according to the NYHA classification and exercise capacity, both in anaemic and non-anaemic patients.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">14,15</span></a> In the “Ferric CarboxymaltOse evaluatioN on per-Formance in patients with IRon deficiency in coMbination with chronic Heart Failure” (CONFIRM-HF) study, improved exercise capacity, symptoms and quality of life; reduced the risk of hospitalisation due to exacerbation of HF in patients with HF and reduced ejection fraction (HR: 0.39; 95% CI: 0.19–0.82; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009).<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">16</span></a> In addition, in a sub-analysis of the FAIR-HF study, an improvement in renal function was observed with this treatment.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a> More recently, in another small study on HF patients with, CKD and iron deficiency anaemia, IV iron therapy was associated with an improvement in myocardial function and heart dimensions.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a> Finally, a recent meta-analysis on the effect of IV iron therapy in patients with HF with reduced ejection fraction and iron deficiency demonstrated a reduction in the composite endpoint of all-cause mortality, cardiovascular death or hospitalisation for HF (OR 0.39; 95% CI: 0.24–0.63; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0001), improvement in functional class (−0.54 class, 95% CI: −0.87 to −0.21; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001), improvement in symptoms (patient global assessment +0.70 points; 95% CI: 0.31–1.09; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0004), exercise capacity (+31<span class="elsevierStyleHsp" style=""></span>m, 95% CI: 18–43; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001), in the six-minute walk test and quality of life measured by different scales.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Given the lack of evidence of benefits from oral iron therapy and the benefit observed with IV ferric carboxymaltose in patients with congestive HF and iron deficiency, it is recommended the administration of IV iron in these patients.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a> In fact, recent guidelines from the European Society of Cardiology (ESC) on HF indicate that treatment with IV ferric carboxymaltose should be considered in symptomatic patients with HF and reduced ejection fraction with iron deficiency in order to improve symptoms, exercise capacity and quality of life (class <span class="elsevierStyleSmallCaps">ii</span>a recommendation and level of evidence A).<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> However, the same guideline highlights that no clinical trial had sufficient statistical power to evaluate the effects on hard clinical events (mortality or cardiovascular events) or to analyse separately the effects on anaemic vs. non-anaemic patients. Finally, the effect of treating iron deficiency in patients with HF and preserved or slightly reduced ejection fraction, and long-term safety of IV iron in this population are unknown. There are currently a number of ongoing clinical trials analysing the effect of administering IV iron on clinically relevant events “Study to compare ferric carboxymaltose with placebo in patients with acute heart failure and iron deficiency” [Affirm-AHF] <a href="ctgov:NCT02937454">NCT02937454</a>, “Effectiveness of intravenous iron treatment vs. standard care in patients with heart failure and iron deficiency: A randomised, open-label multicentre trial” [IRONMAN] <a href="ctgov:NCT02642562">NCT02642562</a>, or the “Intravenous iron in patients with severe chronic heart failure and chronic kidney disease” <a href="ctgov:NCT00384567">NCT00384567</a> that will answer definitively if the benefit of iron therapy in patients with HF and iron deficiency also applies to hard events and improves prognosis in these patients.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathophysiology of iron deficiency in heart failure</span><p id="par0035" class="elsevierStylePara elsevierViewall">Is there a pathophysiological basis explaining this improvement in HF after administration of IV iron, regardless of the presence of anaemia? Iron is essential in the physiology of the myocardiocyte, such as oxygen transport and storage, and energy metabolism (it is a component of the mitochondrial electron transport chain).<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">22,23</span></a> The heart has the highest metabolic demands of the body, and the production of energy, determined to a large extent by mitochondrial function, should adapt to energy requirements.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a> At the tissue level, the iron content in the myocardium is reduced by 20–30% in patients with severe HF.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">25,26</span></a> Thus, small changes in the cardiac energy metabolism may have a significant effect on myocardial contractility. The availability of iron is regulated by two iron regulatory proteins: iron regulatory elements IRP1 and IRP2. In the presence of Iron deficiency, the IRPs interact with iron-responsive elements increasing the stability of the transferrin receptor mRNA and inhibiting the translation of ferroportin and ferritin H- and L-chains which promotes the increase in intracellular iron.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a> A recent study has shown that the activity of IRPs is reduced in HF, which is associated with reductions in transferrin receptor gene expression and tissue concentration of iron.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a> These findings have been confirmed in another study which also demonstrated an association with myocardial mitochondrial dysfunction in patients with HF.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> In the aforementioned publication, the effect of the selective deletion of IRP1 and IRP2 was analysed in the myocardium in an experimental model.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a> These mice were unable to increase the left ventricular function in response to a dobutamine stress test. After a myocardial infarction, they developed a more severe left ventricular dysfunction and had a higher mortality rate due to HF. In addition, the activity of the mitochondrial electron transport chain was decreased in these mice. In another animal model, the specific deletion of the transferrin receptor in the myocardium was associated with myocardial iron deficiency and severe cardiomyopathy.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> In both models, these changes were reversed with the systemic administration of iron.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">28,30</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">A recent pilot study on patients with HF and iron deficiency reported that the administration of IV ferric carboxymaltose was associated with myocardial iron repletion measured by cardiac magnetic resonance imaging, which was associated with left ventricular remodelling.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> Thus, there is evidence of decreased myocardial iron content in HF, and that cellular iron plays a role in the energy generation processes through the mitochondrial respiratory chain. Therefore, a decrease in myocardial iron content could contribute to the pathophysiology of HF. Systemic administration of iron may reverse this situation and improve clinical symptoms in patients with HF.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In summary, HF is highly prevalent in patients with CKD, and vice versa. Iron deficiency is common in this population, and it is associated with a worse prognosis, regardless of the presence of anaemia. The studies completed to date show a beneficial effect of treatment with IV iron therapy in patients with HF with reduced ejection fraction and iron deficiency, regardless of the presence or absence of anaemia. Therefore, in these patients, assessment of iron status and considering the treatment of the iron deficiency is recommended. This represents a conceptual change in patients with HF and CKD compared to what is stated in the treatment guidelines for anaemia in CKD, where iron therapy is only indicated in the presence of anaemia and iron deficiency.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Nephrologists are responsible for the treatment of anaemia in patients with CKD, and act are experts in the management of parenteral iron therapy in CKD and, by extension, in related fields. We should be prepared to join cardiologists in these cases, which are on the borderline between the two specialities. The knowledge and experience accumulated in the management of anaemic patients with CKD may be useful in paving the way for our cardiologist or internal medicine colleagues in the new indications for iron therapy.<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres950353" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec922203" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres950354" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec922202" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Iron deficiency in heart failure" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Pathophysiology of iron deficiency in heart failure" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-11-14" "fechaAceptado" => "2017-03-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec922203" "palabras" => array:4 [ 0 => "Iron deficiency" 1 => "Heart failure" 2 => "Chronic kidney disease" 3 => "IV iron therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec922202" "palabras" => array:4 [ 0 => "Déficit de hierro" 1 => "Insuficiencia cardíaca" 2 => "Enfermedad renal crónica" 3 => "Ferroterapia intravenoso" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a <span class="elsevierStyleItalic">post hoc</span> analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad renal crónica y la anemia son frecuentes en la insuficiencia cardíaca (IC) y su presencia se asocia con un peor pronóstico en estos pacientes. La ferropenia es frecuente en pacientes con IC y aumenta el riesgo de morbimortalidad, independientemente de la presencia o no de anemia. Mientras el tratamiento de la anemia con agentes estimuladores de la eritropoyesis en pacientes con IC no ha demostrado un beneficio sobre la morbimortalidad, el tratamiento con hierro intravenoso (iv) en pacientes con IC y fracción de eyección disminuida y déficit de hierro se asocia con una mejoría clínica. Además, en un análisis <span class="elsevierStyleItalic">post hoc</span> de un ensayo clínico, la ferroterapia mejoró la función renal en pacientes con IC y ferropenia. De hecho, las recientes guías clínicas sobre IC de la Sociedad Europea de Cardiología señalan que se debe considerar el tratamiento con hierro carboximaltosa iv en pacientes sintomáticos con fracción de eyección disminuida y déficit de hierro a fin de mejorar los síntomas, la capacidad de ejercicio y la calidad de vida. El hierro juega un papel importante en el almacenamiento de oxígeno (mioglobina) y en el metabolismo energético, y existen bases fisiopatológicas que explican el efecto beneficioso de la ferroterapia iv en pacientes con IC. Todo ello es revisado en el presente artículo.</p></span>" ] ] "NotaPie" => array:2 [ 0 => array:3 [ "etiqueta" => "◊" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">A list of the members of the group can be found in <a class="elsevierStyleCrossRef" href="#sec0030">Appendix A</a>.</p>" "identificador" => "fn1" ] 1 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Cases Amenós A, Ojeda López R, Portolés Pérez JM, en representación del Grupo de Anemia de la S.E.N. Insuficiencia cardíaca en la enfermedad renal y déficit de hierro: importancia de la ferroterapia. Nefrologia. 2017;37:587–591.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:3 [ "apendice" => "<p id="par0095" class="elsevierStylePara elsevierViewall">Anaemia Group of the Spanish Society of Nephrology (SEN): José María Portolés, coordinator; Ángel Luis Martín de Francisco, Manuel Arias, Pedro Aljama, Juan Manuel López Gómez, José Luis Górriz, Alberto Martínez-Castelao, Aleix Cases, Patricia de Sequera, Borja Quiroga, Raquel Ojeda and Sagrario Soriano.</p>" "etiqueta" => "Appendix A" "identificador" => "sec0030" ] ] ] ] "multimedia" => array:1 [ 0 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Key concepts</span><p id="par0055" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0060" class="elsevierStylePara elsevierViewall">Iron deficiency with and without anaemia is common in patients with HF, and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0065" class="elsevierStylePara elsevierViewall">Iron deficiency in HF is defined by ferritin levels <100<span class="elsevierStyleHsp" style=""></span>μg/l or 100–300<span class="elsevierStyleHsp" style=""></span>μg/l if it is associated with a transferrin saturation level <20%.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0070" class="elsevierStylePara elsevierViewall">There are pathophysiological bases that explain why the correction of iron deficiency in patients with HF and reduced ejection fraction improves the actual clinical situation and the overall prognosis.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0075" class="elsevierStylePara elsevierViewall">The use of parenteral iron therapy, but not ESA, in iron deficient HF patients with reduced ejection fraction improves symptoms, exercise tolerance, quality of life and reduces readmissions. The effects of IV iron therapy on mortality and morbidity are being evaluated in ongoing randomised clinical trials.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0080" class="elsevierStylePara elsevierViewall">In patients with symptomatic HF with reduced ejection fraction and iron deficiency, the administration of IV iron as ferric carboxymaltose should be considered regardless of the presence of anaemia, as presented in the recent HF guidelines from the ESC<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> and the consensus document from the Spanish Society of Cardiology (SEC) and the Spanish Society of Internal Medicine (SEMI).<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> This assumption would be extended to patients with HF and iron deficiency who also have CKD.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0085" class="elsevierStylePara elsevierViewall">After the correction of iron deficiency in these patients, the maintenance doses will depend on the blood count values and the iron kinetics prior to the new dose, in order to avoid an iron overload.</p></li></ul></p></span></span>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0165" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anemia and mortality in heart failure patients a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 77 | 45 | 122 |
| 2024 September | 148 | 40 | 188 |
| 2024 August | 181 | 79 | 260 |
| 2024 July | 134 | 35 | 169 |
| 2024 June | 129 | 50 | 179 |
| 2024 May | 138 | 34 | 172 |
| 2024 April | 103 | 36 | 139 |
| 2024 March | 76 | 29 | 105 |
| 2024 February | 99 | 44 | 143 |
| 2024 January | 81 | 28 | 109 |
| 2023 December | 62 | 40 | 102 |
| 2023 November | 97 | 38 | 135 |
| 2023 October | 95 | 48 | 143 |
| 2023 September | 116 | 47 | 163 |
| 2023 August | 123 | 30 | 153 |
| 2023 July | 101 | 26 | 127 |
| 2023 June | 73 | 16 | 89 |
| 2023 May | 79 | 37 | 116 |
| 2023 April | 56 | 15 | 71 |
| 2023 March | 120 | 31 | 151 |
| 2023 February | 81 | 25 | 106 |
| 2023 January | 82 | 33 | 115 |
| 2022 December | 123 | 44 | 167 |
| 2022 November | 128 | 47 | 175 |
| 2022 October | 169 | 56 | 225 |
| 2022 September | 130 | 63 | 193 |
| 2022 August | 125 | 41 | 166 |
| 2022 July | 131 | 77 | 208 |
| 2022 June | 125 | 49 | 174 |
| 2022 May | 122 | 34 | 156 |
| 2022 April | 203 | 59 | 262 |
| 2022 March | 144 | 56 | 200 |
| 2022 February | 149 | 56 | 205 |
| 2022 January | 118 | 49 | 167 |
| 2021 December | 118 | 54 | 172 |
| 2021 November | 129 | 46 | 175 |
| 2021 October | 128 | 55 | 183 |
| 2021 September | 82 | 51 | 133 |
| 2021 August | 76 | 48 | 124 |
| 2021 July | 78 | 39 | 117 |
| 2021 June | 68 | 33 | 101 |
| 2021 May | 77 | 61 | 138 |
| 2021 April | 180 | 103 | 283 |
| 2021 March | 91 | 54 | 145 |
| 2021 February | 93 | 45 | 138 |
| 2021 January | 63 | 23 | 86 |
| 2020 December | 91 | 23 | 114 |
| 2020 November | 49 | 32 | 81 |
| 2020 October | 52 | 22 | 74 |
| 2020 September | 52 | 35 | 87 |
| 2020 August | 67 | 24 | 91 |
| 2020 July | 66 | 31 | 97 |
| 2020 June | 48 | 23 | 71 |
| 2020 May | 88 | 23 | 111 |
| 2020 April | 71 | 29 | 100 |
| 2020 March | 73 | 25 | 98 |
| 2020 February | 66 | 23 | 89 |
| 2020 January | 97 | 30 | 127 |
| 2019 December | 74 | 28 | 102 |
| 2019 November | 78 | 29 | 107 |
| 2019 October | 77 | 23 | 100 |
| 2019 September | 58 | 19 | 77 |
| 2019 August | 60 | 32 | 92 |
| 2019 July | 57 | 34 | 91 |
| 2019 June | 59 | 28 | 87 |
| 2019 May | 52 | 25 | 77 |
| 2019 April | 99 | 49 | 148 |
| 2019 March | 66 | 29 | 95 |
| 2019 February | 57 | 28 | 85 |
| 2019 January | 32 | 32 | 64 |
| 2018 December | 230 | 42 | 272 |
| 2018 November | 410 | 31 | 441 |
| 2018 October | 306 | 19 | 325 |
| 2018 September | 110 | 13 | 123 |
| 2018 August | 48 | 7 | 55 |
| 2018 July | 48 | 12 | 60 |
| 2018 June | 69 | 13 | 82 |
| 2018 May | 87 | 10 | 97 |
| 2018 April | 116 | 14 | 130 |
| 2018 March | 71 | 15 | 86 |
| 2018 February | 29 | 6 | 35 |
| 2018 January | 25 | 10 | 35 |
| 2017 December | 45 | 10 | 55 |
| 2017 November | 4 | 1 | 5 |
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