Iron Deficiency in Patients with Heart Failure: New Advances in Translational and Clinical Research

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (15 August 2022) | Viewed by 16613

Special Issue Editor

Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
Interests: heart failure; health services and outcomes research; translational research; iron deficiency; eHealth; chronic cardiovascular conditions
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Special Issue Information

 Dear Colleagues,

Heart failure is a devastating syndrome with a very negative impact on mortality, morbidity, and health-related quality of life in patients with this diagnosis. Heart failure also represents a challenge to healthcare systems due to its growing prevalence and the rising medical resource use and expenditure associated with this syndrome. Comorbidities, and particularly iron deficiency, have been identified as a factor that may partially explain the occurrence of major adverse events and limitations in patient-reported outcomes in the setting of heart failure. Recent advances in research have settled the basis of the treatment of iron deficiency and helped to understand the pathophysiological pathways linking iron deficiency and heart failure. However, there are still many gaps of knowledge regarding the complex interplay between iron deficiency and heart failure. In summary, new advances in translational and clinical research will broaden the knowledge of iron deficiency in heart failure and will increase awareness of clinicians about this comorbidity. All these will finally translate into benefits for heart failure patients.

Dr. Josep Comín-Colet
Guest Editor

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Keywords

  • Iron deficiency
  • iron metabolism
  • heart failure
  • comorbidities
  • translational medicine
  • outcomes research
  • anemia

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Published Papers (4 papers)

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Research

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10 pages, 7569 KiB  
Article
Incidence, Treatment and Clinical Impact of Iron Deficiency in Chronic Heart Failure: A Longitudinal Analysis
by Gema Miñana, Miguel Lorenzo, Antonio Ramirez de Arellano, Sandra Wächter, Rafael de la Espriella, Clara Sastre, Anna Mollar, Eduardo Núñez, Vicent Bodí, Juan Sanchis, Antoni Bayés-Genís and Julio Núñez
J. Clin. Med. 2022, 11(9), 2559; https://doi.org/10.3390/jcm11092559 - 02 May 2022
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Abstract
In patients with heart failure (HF), iron deficiency (ID) is a well-recognized therapeutic target; information about its incidence, patterns of iron repletion, and clinical impact is scarce. This single-centre longitudinal cohort study assessed the rates of ID testing and diagnosis in patients with [...] Read more.
In patients with heart failure (HF), iron deficiency (ID) is a well-recognized therapeutic target; information about its incidence, patterns of iron repletion, and clinical impact is scarce. This single-centre longitudinal cohort study assessed the rates of ID testing and diagnosis in patients with stable HF, patterns of treatment with intravenous iron, and clinical impact of intravenous iron on HF rehospitalization risk. We included 711 consecutive outpatients (4400 visits) with stable chronic HF from 2014 to 2019 (median [interquartile range] visits per patient: 2 [2–7]. ID was defined as serum ferritin <100 µg/L, or 100–299 µg/L with transferrin saturation (TSAT) < 20%. During a median follow-up of 2.20 (1.11–3.78) years, ferritin and TSAT were measured at 2230 (50.7%) and 2183 visits (49.6%), respectively. ID was found at 846 (37.9%) visits, with ferritin and TSAT available (2230/4400), and intravenous iron was administered at 321/4400 (7.3%) visits; 233 (32.8%) patients received intravenous iron during follow-up. After multivariate analyses, iron repletion at any time during follow-up was associated with a lower risk of recurrent HF hospitalization (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.28–0.88; p = 0.016). Thus, ID was a frequent finding in patients with HF, and its repletion reduced the risk of recurrent HF hospitalizations. Full article
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17 pages, 1227 KiB  
Article
Expression of Iron Metabolism Proteins in Patients with Chronic Heart Failure
by Bogna Kozłowska, Barbara Sochanowicz, Leszek Kraj, Małgorzata Palusińska, Piotr Kołsut, Łukasz Szymański, Sławomir Lewicki, Witold Śmigielski, Marcin Kruszewski and Przemysław Leszek
J. Clin. Med. 2022, 11(3), 837; https://doi.org/10.3390/jcm11030837 - 05 Feb 2022
Cited by 7 | Viewed by 2218
Abstract
In heart failure, iron deficiency is a common comorbid disease that negatively influences exercise tolerance, number of hospitalizations and mortality rate, and this is why iron iv supplementation is recommended. Little is known about the changes in iron-related proteins in the human HF [...] Read more.
In heart failure, iron deficiency is a common comorbid disease that negatively influences exercise tolerance, number of hospitalizations and mortality rate, and this is why iron iv supplementation is recommended. Little is known about the changes in iron-related proteins in the human HF myocardium. The purpose of this study was to assess iron-related proteins in non-failing (NFH) vs. failing (FH) human myocardium. The study group consisted of 58 explanted FHs; control consisted of 31 NFHs unsuitable for transplantation. Myocardial proteins expressions: divalent metal transporter (DMT-1); L-type calcium channel (L-CH); transferrin receptors (TfR-1/TfR-2); ferritins: heavy (FT-H) or light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN), regulatory factors and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH, the expression in almost all proteins responsible for iron transport: DMT-1, TfR-1, L-CH, except TfR-2, and storage: FT-H/-L/-MT were reduced, with no changes in FPN. Moreover, 4-HNE expression (pg/mg; NFH 10.6 ± 8.4 vs. FH 55.7 ± 33.7; p < 0.0001) in FH was increased. HNE-4 significantly correlated with DMT-1 (r = −0.377, p = 0.036), L-CH (r = −0.571, p = 0.001), FT-H (r = −0.379, p = 0.036), also FPN (r = 0.422, p = 0.018). Reducing iron-gathering proteins and elevated oxidative stress in failing hearts is very unfavorable for myocardiocytes. It should be taken into consideration before treatment with drugs or supplements that elevate free oxygen radicals in the heart. Full article
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19 pages, 2181 KiB  
Article
Blood Differential Gene Expression in Patients with Chronic Heart Failure and Systemic Iron Deficiency: Pathways Involved in Pathophysiology and Impact on Clinical Outcomes
by Carles Díez-López, Marta Tajes Orduña, Cristina Enjuanes Grau, Pedro Moliner Borja, José González-Costello, Elena García-Romero, Josep Francesch Manzano, Sergi Yun Viladomat, Santiago Jiménez-Marrero, Raul Ramos-Polo, Maria del Mar Ras Jiménez and Josep Comín-Colet
J. Clin. Med. 2021, 10(21), 4937; https://doi.org/10.3390/jcm10214937 - 26 Oct 2021
Cited by 6 | Viewed by 2205
Abstract
Background: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in [...] Read more.
Background: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in this crosstalk are yet to be unfolded. Methods: The present research attempts to investigate the intrinsic biological mechanisms between heart failure and iron deficiency and to identify potential prognostic biomarkers by determining the gene expression pattern in the blood of heart failure patients, using whole transcriptome and targeted TaqMan® low-density array analyses. Results: We performed a stepwise cross-sectional longitudinal study in a cohort of chronic heart failure patients with and without systemic iron deficiency. First, the full transcriptome was performed in a nested case-control exploratory cohort of 7 paired patients and underscored 1128 differentially expressed transcripts according to iron status (cohort1#). Later, we analyzed the messenger RNA levels of 22 genes selected by their statistical significance and pathophysiological relevance, in a validation cohort of 71 patients (cohort 2#). Patients with systemic iron deficiency presented lower mRNA levels of mitochondrial ferritin, sirtuin-7, small integral membrane protein 20, adrenomedullin and endothelin converting enzyme-1. An intermediate mitochondrial ferritin gene expression and an intermediate or low sirtuin7 and small integral membrane protein 20 mRNA levels were associated with an increased risk of all-cause mortality and heart failure admission ((HR 2.40, 95% CI 1.04–5.50, p-value = 0.039), (HR 5.49, 95% CI 1.78–16.92, p-value = 0.003), (HR 9.51, 95% CI 2.69–33.53, p-value < 0.001), respectively). Conclusions: Patients with chronic heart failure present different patterns of blood gene expression depending on systemic iron status that affect pivotal genes involved in iron regulation, mitochondrial metabolism, endothelial function and cardiovascular physiology, and correlate with adverse clinical outcomes. Full article
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Review

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30 pages, 3534 KiB  
Review
Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology
by Ridha I. S. Alnuwaysir, Martijn F. Hoes, Dirk J. van Veldhuisen, Peter van der Meer and Niels Grote Beverborg
J. Clin. Med. 2022, 11(1), 125; https://doi.org/10.3390/jcm11010125 - 27 Dec 2021
Cited by 43 | Viewed by 12951
Abstract
Iron is an essential micronutrient for a myriad of physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF), with a prevalence reaching up to 59% even in non-anaemic patients. ID impairs exercise [...] Read more.
Iron is an essential micronutrient for a myriad of physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF), with a prevalence reaching up to 59% even in non-anaemic patients. ID impairs exercise capacity, reduces the quality of life, increases hospitalisation rate and mortality risk regardless of anaemia. Intravenously correcting ID has emerged as a promising treatment in HF as it has been shown to alleviate symptoms, improve quality of life and exercise capacity and reduce hospitalisations. However, the pathophysiology of ID in HF remains poorly characterised. Recognition of ID in HF triggered more research with the aim to explain how correcting ID improves HF status as well as the underlying causes of ID in the first place. In the past few years, significant progress has been made in understanding iron homeostasis by characterising the role of the iron-regulating hormone hepcidin, the effects of ID on skeletal and cardiac myocytes, kidneys and the immune system. In this review, we summarise the current knowledge and recent advances in the pathophysiology of ID in heart failure, the deleterious systemic and cellular consequences of ID. Full article
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