Anemia In Chronic Heart Failure Research Articles

Clinical significance of anemia in chronic heart failure in patients infected with human immunodeficiency virus

Anemia, as the most common hematological complication of HIV infection, is one of the key indicators of its severity and a predictor of death from its complications. Within 3 years, 240 patients with HIV infection were examined in a multidisciplinary hospital. In the examined group, 160 (66.60 %) people had clinical, instrumental and laboratory signs of CHF. Among them, 94 patients (58.75 %) had anemia of varying severity. The presence of CHF 2.75 times increases the chances of developing anemia in HIV-infected people. The development of anemia is associated with the development of CKD stage 3A and above, an increase in the volume of the left atrium, the development of diastolic dysfunction of the left ventricle and severe CHF with a concentration of NT-proBNP ≥ 1500 pg/ml in blood plasma. In patients with CHF and HIV infection, determining the concentration of NT-proBNP ≥ 170 pg/ml is associated with the development of anemia, which gives this test additional clinical significance. Reduced transferrin less than 200 mg/dl 10.99 times increases the chances of developing severe CHF with NT-proBNP ≥ 1500 pg/ml, which makes it recommended to determine the level of serum transferrin in all patients with HIV infection and CHF in order to predict the development of severe CHF with NT-proBNP ≥ 1500 pg/ml.

New possibilities of pathogenetic correction of anemia in chronic heart failure

If chronic heart failure (CHF) is accompanied by anemic syndrome and iron defi ciency (ID) tolerance to treatment develops, the eff ectiveness of drugs that form the basis of CHF treatment decreases, and the prognosis worsens. Aim. To evaluate the possibilities of using iron preparations with hepcidin-independent absorption mechanism depending on the characteristics of iron metabolism, erythropoiesis and the level of infl ammation in patients with CHF and anemia. Material and methods. The study included 68 patients diagnosed with CHF to describe the characteristics of anemia (General group). Further, 56 patients who signed consent to the study were divided into two groups: 30 patients (Treatment Group) with standard CHF therapy and iron preparations, and 26 (Comparison Group) with standard CHF therapy only. Sucrosomial iron (SI) was used 60 mg per day orally for three months. Results. Variants of anemia in CHF: absolute ID (AID) — 43%, functional ID (FID) — 19%, anemia without ID — 38%. In the treatment group, an increase in hemoglobin (Hb, p < 0.002), hematocrit (Ht, p < 0.001), mean corpuscular volume (MCV, p < 0.002) and serum ferritin (SF, p < 0.05), in the Сomparison group only Ht, p < 0.01, and the greatest increase in Hb was detected in patients with SF < 30 μmol/l (p < 0.002). Conclusion. Anemia in CHF corresponds to the signs of anemia of chronic disease (ACD) with J, while J was detected in 62% of patients. The use of SI signifi cantly increases erythrocyte counts and SF/

The Risk Of Developing Anemia In Patients With Chronic Heart Failure And Its Prognostic Value

Analysis of modern views on the problem of anemia in chronic heart failure (CHF), on the main pathogenetic mechanisms of its formation and the possibility of drug correction. The CHF problem has a number of interdisciplinary aspects. One of the pathologies often encountered in CHF is anemia, which aggravates hemodynamic disturbances and worsens the prognosis in patients. Understanding the mechanisms of the development of anemia in CHF is of great importance for the choice of treatment tactics. The review discusses the views on the pathogenetic mechanisms of the formation of anemic syndrome in patients with CHF. The approaches to its treatment from the point of view of pathogenesis are considered. Anemia in CHF is associated with an increased risk of death, worsening of the course of concomitant diseases and an increase in the functional class of heart failure, but it is a potentially reversible condition.

Vitamin D deficiency and anemia is highly prevalent and dependent on the etiology of heart failure: A pilot study.

Anemia and vitamin D deficiency are common factors in chronic heart failure (CHF). The aim of this study was to assess vitamin D levels as well as its binding protein and anemia in relation to a cause of CHF: coronary heart disease, valvular disease and cardiomyopathy. One hundred and sixteen consecutive patients (36 females and 80 males) with CHF were admitted for percutaneous coronary interventions (PCI). Hemoglobin concentration, serum creatinine, B-type natriuretic peptide (BNP), 25-hydroxyvitamin D [25(OH)D] and its binding protein-VDBP were measured. The prevalence of anemia was 22%. BNP was the highest in the group with coronary artery disease. Ejection fraction was the lowest in cardiomyopathy group. 25(OH)D was lowest in valvular disease group, significantly lower than in the coronary artery group. A similar pattern of change showed vitamin D binding protein. The prevalence of vitamin D deficiency (level below 20 ng/mL) in the whole group was 95%, in 49% of the patients 25(OH)D was below 10 ng/mL. In univariate analysis 25(OH)D correlated with hemoglobin, red blood cell count, hematocrit, mean corpuscular volume and BNP in patients with CHF in the whole group. In multiple regression analysis, predictors of 25(OH)D were estimated, glomerular filtration rate, BNP and valvular disease. 25(OH)D deficiency is common in CHF patients. Valvular disease is associated the most severe vitamin D deficiency and worsened kidney function. A higher prevalence of anemia in CHF due to coronary heart disease may be associated with wider use of angiotensin converting enzyme inhibitors and acetylsalicylic acid. Heart and kidney function are predictors of 25(OH)D level in the patients of this study.

Cytokine-induced inflammation in anemia in patients with chronic heart failure

Introduction.Anemic syndrome (AS) is a common pathological condition in patients with chronic heart failure (CHF) and is recognized as an independent predictor of poor prognosis. A particular role is played by pathogenetically associated with CHF anemia. Mechanisms of its occurrence are being studied. An important role belongs to systemic inflammation, which is involved in the pathogenesis of anemia of chronic diseases (ACD). However, the contribution of cytokine-induced inflammation in patients with heart failure has not yet been fully investigated.Material and methods.A total of 873 cases of patients with CHF were prospectively analyzed on the basis of the cardiology department of the SBHCI NNR «Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko». The main group consisted of patients with anemia pathogenetically associated with heart failure (n = 96), the control group (CG) (n = 35) patients with heart failure without anemia. The indicators of ferrokinetics were assessed and the systemic inflammation was compared by indicators of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and serum hepсidin.Results.Patients of the main group had signs of functional iron deficiency (ID) and significantly higher values of cytokines and hepsidin compared with the CG. The relationship between the level of cytokines and hepsidin with the severity of CHF, hemogobin and chronic kidney disease was revealed.Conclusion.An increase in the concentration of pro-inflammatory cytokines and hepcidin in patients with AS with decompensation of CHF is interrelated with functional ID and a decrease in hemoglobin level. This shows the role of cytokine-induced inflammation in the genesis of anemia in heart failure. The functional state of the kidneys makes a special contribution to these mechanisms. As CKD increases, the levels of inflammatory cytokines and hepcidin in these patients and their relationship with markers (CKD) increase.

IRON DEFICIENCY AND ANEMIA IN PATIENTS WITH CHRONIC HEART FAILURE

Problems of iron deficiency and anemia in chronic heart failure (CHF) are discussed in the article. A review of the literature on the epidemiology, etiology and pathogenesis of anemia in this category of patients is presented. Various published data on the effect of anemia on the prognosis of CHF are given. The role of iron deficiency in the development of anemia, the features of its diagnosis and influence on the course of CHF are discussed. The author explains the role of various iron deficiency syndromes in the development of anemia in CHF, suggests a significant predominance of mixed forms of iron deficiency, such as iron deficiency anemia in combination with anemia of chronic disease, which are associated not so much with absolute iron deficiency as with systemic inflammatory response. All the existing approaches to the treatment of iron deficiency and anemia in patients with CHF are presented. The positive and negative results of the use of classical oral iron preparations, intravenous forms, isolated and combined use of recombinant human erythropoietin are presented. The author discusses the reasons for the failure in the treatment of anemia and the absence of a pronounced effect on the clinical manifestations of CHF in the application of standard approaches in treatment. As a possibility of more effective correction of iron deficiency and anemia in patients with CHF, new preparations of liposomial (sucrosomial) iron for oral administration are offered. The last extremely encouraging clinical results of the use of a new iron formulation in the treatment of iron deficiency and anemia in this group of patients are given.

O5-1 - Gender and Prognostic Significance of Anemia in Chronic Heart Failure

O5-1 - Gender and Prognostic Significance of Anemia in Chronic Heart Failure

The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials

BackgroundAlthough anemia is common in chronic heart failure (CHF), the use of erythropoiesis stimulating agents (ESAs) in CHF patients remains controversial. In this meta-analysis, we sought to clarify the efficacy and safety of ESAs in anemic patients with CHF. MethodsWe searched PubMed, Embase, Cochrane Central Register of Controlled Trials, the U.S. National Institutes of Health registry of clinical trials. We included 13 randomized clinical trials (RCTs) in the meta-analysis. The co-primary outcome was all-cause mortality and rehospitalization. The safety analysis outcome was thromboembolic events. ResultsPreliminary analysis showed that ESA-treatment did not have any effect for all-cause mortality and rehospitalization. However, we revealed a significant small-study bias, and used the trim-and-fill method to reduce this bias. The summary effect of ESA-treatment was insignificant for all-cause mortality (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.59–1.42, p=0.69) and for rehospitalization (RR 0.91, 95% CI 0.67–1.23, p=0.53). Regarding symptoms, ESA-treatment improved dyspnea (NYHA grade improvement: 1.63, 95% CI 0.65–2.62, p<0.001) and quality-of-life measured by subjective questionnaires. However, in safety analysis, ESAs increased the over-all risk for thromboembolic events (RR 1.28, 95% CI 1.03–1.58, p=0.026), however, no specific increase was observed in severe thromboembolic events. Subgroup analysis showed no difference in ESA-treatment according to the type of ESAs (darbepoetin vs. erythropoietin) and between studies of different follow-up durations (<6months or ≥6months). ConclusionAmong CHF patients with anemia, ESA-treatment has a neutral effect on all-cause mortality and rehospitalization and improves symptoms, but has harmful effects on thromboembolic events.

24 Anaemia in heart failure unit St. Michaels hospital dun laoghaire

Background Iron deficiency anaemia is a frequent finding in adults with heart failure (HF). The prevalence varying depending upon the population studied. 1,2 The recent FAIR-HF trial, demonstrates the importance of iron metabolism in patients with HF. 3 Moreover, that a work-up evaluation for absolute or functional iron deficiency should be considered, and implementation of IV iron replacement for symptomatic improvement. In this audit we wish to evaluate the prevalence of anaemia and iron deficiency in our unit Method This was a prospective single centre audit between 21 October and 18 November 2014. The cycle was repeated between 26 March and 26 April 2015. The audit standard was the WHO definition of anaemia. Results Part 1: Demographics During cycle 1 Population: 86 patients were worked up for anaemia and iron deficiency. The average follow up time in Heart Failure Unit was 19.6 months There were more males than females in our population. Only one female patient is still menstruating. 74% of our population are HfREF (n = 64) versus 26% HfPEF (n = 22). During cycle 2 Population: 56 patients were worked up for anaemia and iron deficiency. The average follow up time in Heart Failure Unit was 20.4 months. There were more males than females in our population. 57% of our population are HfREF (n = 31) versus 43% HfPEF (n = 23). Part 2: Prevalence and incidence The prevalence of anaemia in our cohort was 48% during cycle 1 and 64.8% during cycle 2. Previous studies have found that the incidence of anaemia appears to increase with worsening functional class (from 9% for NYHA class I to 79% for class IV in one report). 4,5 We found no association between the incidence of anaemia for NYHA, BNP or EF in our cohort. Part 3: Haematinic Screen Haematinic screens were not routinely ordered on all anaemic patients during cycle 1. No haematinic screen was found for 15 anaemic patients, an incomplete screen was carried out on 9 anaemic patients and a complete anaemic screen on 17 patient. A complete haematinic screen was carried out on 8 patients with normal Hb levels. Iron deficency was detected in 17 patients. Five patient with iron deficency were noted to have a normal Hb level. During cycle 2 and implementation of a routine strategy of a haematinic screening at initial programme visit or at annual review, if no such screen were on record, all patients had a haematinic screen. Summary Iron deficiency management is not incorporated in the current ESC HF guidelines. 6 However, recent studies have raised interest in the importance in symptomatic and QUAL in of HfREF patients, and experts anticipate it’s inclusion in future guidelines. Further given that there are few treatment strategies for HfPEF patients, management of iron deficiency in this cohort would be an area of interest to access any symptomatic and other clinical benefit. In this audit we successfully implemented a strategy of routine screening for iron deficiency, to capture all patients in both HfREF and HfPEF patients. Importantly, at present our cohort our stable from a heart failure perspective. In future direction and management of these patients we aim to implement a strategy of IV iron replacement based on recent FAIR-HF and CONFIRM-HF studies. 3,7 References De Silva R, Rigby AS, Witte KK, et al . Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol. 2006; 98 :391–398 Westenbrink BD, Visser FW, Voors AA, et al . Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J. 2007; 28 :166–171 Anker SD, Comin Colet J, Filippatos G, et al . Rationale and design of Ferinject assessment in patients with iron deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail . 2009; 11 :1084–1091 Silverberg DS, Wexler D, Sheps D, et al . The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol . 2001; 37 :1775–1780 Van der Meer P, Groenveld HF, Januzzi JL Jr, et al . Erythropoietin treatment in patients with chronic heart failure: a meta-analysis. Heart 2009; 95 :1309–1314 McMurray J, Adamopoulos S, Anker S, et al . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur Heart J . 2012; 33 :1787–1847 Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al . Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J . 2015; 36 (11):657–68

Prevalence of anaemia in chronic heart failure and contribution of Iron deficiency and renal dysfunction as underlying cause

Prevalence of anaemia in chronic heart failure and contribution of Iron deficiency and renal dysfunction as underlying cause

RED CELL DISTRIBUTION WIDTH IN HEART FAILURE: A MULTIMARKER OF DIFFERENT PATHOPHYSIOLOGICAL PATHWAYS

BackgroundRed Cell Distribution Width (RDW), a measure of the variation in volume of the red blood cells, has gained popularity in recent years as a strong prognostic marker for multiple clinical outcomes in heart failure (HF). Although many hypotheses to explain this correlation exist, the exact pathophysiological explanations remain unclear.ObjectiveWe aimed to study the relationship between RDW and multiple biomarkers in anemic and non-anemic patients with HF and reduced ejection fraction (HFrEF) using history, physical examination and echocardiographic data as well as a number of serum biomarkers in order to elucidate the pathophysiological links between RDW and HF.Methods and resultsThis report is part of the Anemia in Chronic Heart Failure: Etiology, Comparisons with Renal Disease, and Relationships with Biomarkers and Left Ventricular Remodeling (ANCHOR) study, which recruited 102 patients with HFrEF, with or without anemia in seven Canadian centers. A large number of laboratory, clinical and echocardiographic data were collected and correlations between RDW and biomarkers of interest were studied using linear and multivariate regressions. As expected, RDW was significantly higher in anemic patients compared to non-anemic patients. We identified relationships between RDW and markers of cardiac remodelling (PIIINP, osteopontin, TIMP 1, NT-proBNP, MMP-2 and troponin) renal dysfunction (creatinine, urea, potassium, EPO level, cystatin C and NGAL) markers of inflammation (sedimentation rate, HS-CRP, TGF-beta 1, IL-6 and fibrinogen) as well as markers of erythropoieitic activity (EPO level, soluble transferrin receptor and STfR-F index).Conclusion BackgroundRed Cell Distribution Width (RDW), a measure of the variation in volume of the red blood cells, has gained popularity in recent years as a strong prognostic marker for multiple clinical outcomes in heart failure (HF). Although many hypotheses to explain this correlation exist, the exact pathophysiological explanations remain unclear. Red Cell Distribution Width (RDW), a measure of the variation in volume of the red blood cells, has gained popularity in recent years as a strong prognostic marker for multiple clinical outcomes in heart failure (HF). Although many hypotheses to explain this correlation exist, the exact pathophysiological explanations remain unclear. ObjectiveWe aimed to study the relationship between RDW and multiple biomarkers in anemic and non-anemic patients with HF and reduced ejection fraction (HFrEF) using history, physical examination and echocardiographic data as well as a number of serum biomarkers in order to elucidate the pathophysiological links between RDW and HF. We aimed to study the relationship between RDW and multiple biomarkers in anemic and non-anemic patients with HF and reduced ejection fraction (HFrEF) using history, physical examination and echocardiographic data as well as a number of serum biomarkers in order to elucidate the pathophysiological links between RDW and HF. Methods and resultsThis report is part of the Anemia in Chronic Heart Failure: Etiology, Comparisons with Renal Disease, and Relationships with Biomarkers and Left Ventricular Remodeling (ANCHOR) study, which recruited 102 patients with HFrEF, with or without anemia in seven Canadian centers. A large number of laboratory, clinical and echocardiographic data were collected and correlations between RDW and biomarkers of interest were studied using linear and multivariate regressions. As expected, RDW was significantly higher in anemic patients compared to non-anemic patients. We identified relationships between RDW and markers of cardiac remodelling (PIIINP, osteopontin, TIMP 1, NT-proBNP, MMP-2 and troponin) renal dysfunction (creatinine, urea, potassium, EPO level, cystatin C and NGAL) markers of inflammation (sedimentation rate, HS-CRP, TGF-beta 1, IL-6 and fibrinogen) as well as markers of erythropoieitic activity (EPO level, soluble transferrin receptor and STfR-F index). This report is part of the Anemia in Chronic Heart Failure: Etiology, Comparisons with Renal Disease, and Relationships with Biomarkers and Left Ventricular Remodeling (ANCHOR) study, which recruited 102 patients with HFrEF, with or without anemia in seven Canadian centers. A large number of laboratory, clinical and echocardiographic data were collected and correlations between RDW and biomarkers of interest were studied using linear and multivariate regressions. As expected, RDW was significantly higher in anemic patients compared to non-anemic patients. We identified relationships between RDW and markers of cardiac remodelling (PIIINP, osteopontin, TIMP 1, NT-proBNP, MMP-2 and troponin) renal dysfunction (creatinine, urea, potassium, EPO level, cystatin C and NGAL) markers of inflammation (sedimentation rate, HS-CRP, TGF-beta 1, IL-6 and fibrinogen) as well as markers of erythropoieitic activity (EPO level, soluble transferrin receptor and STfR-F index). Conclusion

Different Impact of Anemia in Chronic Heart Failure with Preserved vs. Reduced Ejection Fraction -A Report from the CHART-2 Study-

Different Impact of Anemia in Chronic Heart Failure with Preserved vs. Reduced Ejection Fraction -A Report from the CHART-2 Study-

Anaemia in chronic heart failure: more awareness is required

To determine the characteristics of anaemic patients, how well anaemia is investigated and its contributing factors in patients with chronic heart failure (CHF). Retrospective analysis of longitudinal data collected during routine management of patients admitted with CHF at an Australian tertiary hospital. One thousand and twenty-one patients admitted with CHF between 1997 and 2005 were included. Anaemia was defined as a haemoglobin concentration <110 g/L. Data were compared between anaemic and non-anaemic patients. The prevalence of anaemia among patients with CHF was 20.3% in our study. These patients were more likely to be older, female, and have a higher prevalence of chronic renal failure and peripheral vascular disease. Despite previous studies reporting a higher mortality rate among CHF patients with anaemia, only 60% of patients had basic investigations for anaemia (i.e. iron studies, vitamin B12, folate and thyroid function testing). The cause of anaemia is usually multifactorial with 63.8% of patients having at least two factors contributing to their anaemia. Chronic renal failure, iron deficiency and anaemia of chronic disease were the most common contributors. These factors were not predicted based on abnormalities in mean corpuscular volume. Patients with anaemia had a longer length of stay in hospital. Anaemia in patients with CHF is common but not well investigated. The aetiology of anaemia is usually multifactorial and not easily predicted. Patients with anaemia and CHF have poorer outcomes. There needs to be more awareness among clinicians about the importance of investigating and treating anaemia in patients with CHF.

Herzinsuffizienz und Anämie

Chronic heart failure has an age-dependent prevalence of 2% and is therefore one of the most frequent diseases in western societies. A reduced hemoglobin concentration according to the definition of the World Health Organization is a common comorbidity affecting more than half of all heart failure patients. Elderly patients, patients suffering from renal impairment and women are more likely to develop anemia but a definitive etiology of anemia is only identified in the minority of cases. Anemia is associated with a poor clinical status and a greater risk of hospitalization and is a predictive factor for increased mortality. The incidence of anemia appears to increase with a poorer functional class. Intravenous iron therapy improves the exercise capacity in patients with systolic heart failure and iron deficiency and is currently being recommended for patients with persistent symptoms despite optimal medical and device therapy. However, erythropoietin-stimulating agents as a treatment for anemia in chronic heart failure have failed to improve clinical outcome in a large randomized trial. In patients with heart failure but with maintained ejection fraction, anemia is also associated with a poor prognosis. Specific therapeutic recommendations for these patients are still not available.

PC-FACS

PC-FACS

Methoxy polyethylene glycol epoetin beta and the treatment of anaemia in chronic heart failure

Aim. To study erythropoietic activity and safety of methoxy polyethylene glycol epoetin beta (MEB) and its effects on haemoglobin (Hb), erythropoietin, ferritin, NT-proBNP, cytokines, and chronic heart failure (CHF) symptoms and signs. Material and methods . In total, 84 patients with Functional Class (FC) II–IV (NYHA) CHF and anaemia were examined (mean age 59,7±1,6 years; 54 men and 30 women). Anaemia criteria were Hb levels &lt;120 g/l in men and &lt;110 g/l in women. CHF was due to coronary heart disease, CHD (post-infarction cardiosclerosis; n=40); to CHD in combination with Type 2 diabetes mellitus, DM-2 (n=10), and arterial hypertension, AH (n=14); and to the combination of CHD, AH, and DM-2 (n=10). Left ventricular ejection fraction (LVEF) in CHF patients with FC II, III, and IV was

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

AimsAnaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subsequent to diminished erythropoiesis as a result of an immune-mediated suppression of erythroid colony formation. MethodsWe studied 61 CHF patients and 20 healthy control subjects. Circulating primitive haematopoietic (CD34+) and erythroid precursor cells were quantified by flow cytometry. Circulating erythroid progenitors (BFU-E) were cultured in methylcellulose in the presence and absence of monocytes and sera, and with anti-TNFα neutralising antibodies. ResultsDespite higher erythropoietin levels, anaemic patients exhibited lower absolute reticulocyte counts and reticulocyte production indices (P<0.001) than non-anaemic patients and healthy controls. Diminished erythropoiesis was paralleled by attenuated circulating CD34+, erythroid progenitor and precursor cells in anaemic patients (all P<0.01). Depletion of monocytes from cultures derived only from anaemic patients enhanced BFU-E growth (P=0.03). Only the addition of monocytes and sera from anaemic patients suppressed autologous or allogeneic BFU-E colony formation (P=0.02). Serum TNFα levels were highest in anaemic patients and anti-TNFα neutralising antibodies partly abrogated the inhibitory effects of anaemic sera on erythroid colony growth (P=0.03). ConclusionUnexplained anaemia in patients with CHF results partly from suppressed erythropoiesis and monocytes, via a direct effect of TNFα on erythroid cells, orchestrate a degree of this suppression.

Anemia in chronic heart failure: Can we treat? What to treat?

Even though anemia is a significant comorbidity regularly observed in patients with chronic heart failure (HF), only in recent years systematic therapeutic research has been started. This article aims to review the aspects of anemia in chronic HF that are relevant for making treatment decisions, beginning with the definition of anemia and its incidence and prevalence of anemia in patients with chronic HF. Considering the etiology and prognostic impact of anemia in chronic HF, several treatment options will be considered. The latter are the application of erythropoiesis-stimulating agents (erythropoietin or darbepoetin alfa) or in the application of intravenous iron (e.g., iron carboxymaltose). According to the results seen in the FAIR-HF trial, iron supplementation should be particularly considered to improve symptoms and quality of life. Intravenous iron application may result in higher compliance and much faster treatment response than oral iron. The RED-HF study will show whether use of darbepoetin alfa in anemic patients with chronic HF will reduce the combined endpoint of death for any reason or hospitalization for heart failure.

Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK–STAT signal transduction

BackgroundChronic heart failure (CHF) patients are frequently anaemic despite elevated endogenous erythropoietin (Epo) levels. We tested the hypothesis that this might be due to Epo resistance and investigated whether any defects apparent were due to Epo receptor (EpoR) downregulation and/or impaired Epo-induced signal transduction. MethodsWe studied 28 CHF patients (age 64±10yrs, LVEF 29±9%, 89% male) and 12 healthy controls (65±11yrs, 75% male). Circulating erythroid progenitors (BFU-E) were cultured with 0, 1, 3 and 9U/mL Epo. Circulating erythroblast surface EpoR and intracellular phosphorylated Signal Transducer and Activator of Transcription (phosphoSTAT)-5 expression were determined by flow cytometry. ResultsWhilst BFU-E from control and non-anaemic subjects required only 3U/mL Epo to significantly increase their numbers from baseline (1U/mL), those from anaemic patients required 9U/mL Epo. Lower Epo sensitivities related to higher interleukin-6 (r=−0.41, P=0.01) and soluble tumour necrosis factor receptor 2 (r=−0.38, P=0.02) levels. EpoR-positive cells were more abundant in anaemic patients (P<0.001). Although erythroblasts from anaemic patients exhibited higher baseline EpoR and phosphoSTAT5 expression (all P<0.05), Epo stimulation triggered significant increases in phosphoSTAT5 levels only in erythroblasts from control subjects and not in those from anaemic patients. ConclusionThe responsiveness of erythroid cells to Epo is diminished in anaemic CHF patients. This is not due to EpoR downregulation but relates to a profound blunting of Epo-induced JAK–STAT signalling. Whilst residual Epo sensitivity can be exploited clinically with erythropoietic agents, targeting the mechanisms underlying Epo resistance in CHF may provide greater efficacy.

Anemia in Heart Failure: an Overview of Current Concepts

Chronic heart failure is a substantial public health problem. Anemia is an important comorbidity frequently observed in patients with the disease and, in heart failure, anemia has only recently started to attract systematic epidemiological and therapeutical research endeavor. This article describes the many aspects of anemia in chronic heart failure, starting with the ongoing discussion of how to define anemia, which has important consequences for the estimation of its prevalence and incidence. Further, we discuss prognostic implications of anemia in patients with chronic or acute heart failure, the etiology of anemia in heart failure and treatment possibilities. Such therapeutic avenues embrace intravenous iron preparations and subcutaneous administration of erythropoietin and its derivatives, all of which have been extensively studied over the last several years. Finally, this article describes the potential costs incurred by treating anemic patients with heart failure.