Anemia In Chronic Heart Failure Research Articles

Anaemia and heart failure

Abstract Anaemia is one of the most frequent co-morbidities in patients with heart failure. Its prevalence increases from 4% to7% in subjects with asymptomatic left ventricular dysfunction to >30% in patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in providing evidence that anaemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still not fully understood. Moreover a favourable effect of the correction of anaemia on prognosis has not yet been shown. Also In addition to this, controlled studies assessing its effects on exercise tolerance have yielded controversial results. Further research is needed to assess the effect of correcting anaemia in chronic heart failure (CHF) patients; ongoing reduction of events with RED-HF (Darbepoetin alpha in heart failure) trial will help define the role.

Therapy for Anemia in Chronic Heart Failure: Efficacy of Erythropoietin

Silverberg et al proposed the concept that heart failure, chronic kidney disease(CKD), and anemia reciprocally worsen each other, referred to as the Cardio Renal Anemia syndrome. Sixty percent of heart failure patients have CKD, which is complicated by anemia in a high proportion of them. Furthermore, anemia is not only a factor that worsens heart failure, but is also an independent risk factor determining prognosis. In therapy for anemia in heart failure how to maintain the Hb level is an important issue, and erythropoietin(EPO) administration appears promising.

Hepcidin Does Not Mediate Anemia in Chronic Heart Failure Patients and Is Suppressed in Chronic Heart Failure

Background: Hepcidin is an antimicrobial protein that is upregulated in chronic inflammation and regulates iron homeostasis. Very little is currently known about whether hepcidin affects the anemia in chronic heart failure. Furthermore, it is unknown if the inflammatory milieu in heart failure leads to upregulation of hepcidin. Hypothesis: We postulated that serum and urine hepcidin levels are upregulated in heart failure compared to control subjects. Methods: We prospectively enrolled 36 anemic and 61 non-anemic patients with heart failure (HF) and 38 control subjects without HF and measured their serum and urine hepcidin concentrations using mass spectrometry.

Mediators of Anemia in Chronic Heart Failure

Anemia is highly prevalent in patients with chronic heart failure (CHF) and is associated with poor clinical outcome. Increased prevalence of anemia in CHF has been linked to advanced age, female gender, renal function impairment, severity of symptoms, and clinical settings. Overall, the anemia of CHF shares many common features with the anemia of chronic disease. Both impaired iron metabolism and inflammatory stress appear to be the key mediators of the anemia of CHF.

Anemia in chronic heart failure: A review

Despite advances in chronic heart failure (CHF) medical and device therapy in recent years, CHF continues to be a syndrome associated with significant morbidity and mortality. Abundance of data suggests that anemia is prevalent in CHF. The pathophysiology of CHF-related anemia is complex and poorly understood. Earlier small trials demonstrated improvement in morbidity with use of erythropoietin stimulating agents (ESA) and parenteral iron but that was not supported by more recent large randomized trials. There is a concern regarding the safety of ESA. Small studies showed benefits from parenteral iron alone or combination with ESA. This was promising since parenteral iron is a relatively cheap therapeutic intervention to treat anemia in CHF patients. So far there are no clear recommendations regarding the treatment of CHF related anemia. The purpose of this article is to review the most recent epidemiology, pathophysiology, and therapeutic options for anemia in CHF.

108 Importance of haemodilution in haemoglobin concentrations in outpatients with chronic heart failure. Results of IMPACT-RECO Program III

The prevalence of anaemia in chronic heart failure (CHF) ranges widely from 4 to 70% due to a lack of an established consistent definition of anaemia in CHF. Furthermore haemodilution impacts haemoglobin concentrations and could be an important cause of anaemia in CHF. The IMPACT-RECO program III analysed the impact of NYHA class of CHF and of comorbidities on therapeutic management of French outpatients with stable CHF and left ventricular systolic dysfunction. This survey was carried out from March 2007 to December 2007 among randomly selected French private cardiologists. 1574 patients with CHF and left ventricular ejection fraction (LVEF) < 40% were included. Mean age was 71 ± 11 years, 75% of the patients were men, 34% were in NYHA class III-IV, 54% had coronary artery diseases, 30% had atrial fibrillation and the mean LVEF was 34 ± 7%. Haemoglobin concentration was recorded in 953 patients. Anemia was defined as a haemoglobin concentration < 12 g/L in women and < 13 g/L in men. The impact of NYHA class and congestive status in haemoglobin concentrations are summarized in the table. Congestive status impacts haemoglobin concentrations more than the severity of CHF estimated by NYHA class. Haemodilution is an important aetiology of anaemia in CHF, thus haemoglobin concentration should be evaluated if possible in patients without congestive signs. Haemoglobin (g/L) NYHA I NYHA II without congestive signs NYHA II with congestive signs NYHA III NYHA IV n 107 448 62 295 37 Men 13.3 ± 1.6 13.4 ± 1.7 12.1 ± 1.9 12.7 ± 1.8 13.4 ± 1.6 Women 12.7 ± 1.2 12.6 ± 1.3 11.8 ± 2.5 12.1 ± 1.6 12.2 ± 2.1 Anaemia N (%) 33 (30.8) 150 (33.5) 42 (67.7) ** 149 (50.5) * 15 (40.5) * p < 0.05: NYHA III vs NYHA I,II / ** p < 0.05 : NYHA II with congestive signs vs NYHA I,II without congestive signs III,IV.

Iron Regulatory Hormone Hepcidin Decreases in Chronic Heart Failure Patients With Anemia

The etiology of anemia is still unclear in patients with chronic heart failure (CHF). Hepcidin is an iron regulatory peptide that is synthesized in the liver to suppress iron absorption and utilization. Hepcidin synthesis is suppressed by anemia, hypoxia and erythropoiesis, and induced by inflammation. Inflammatory cytokines, such as interleukin-6 (IL-6), increase the synthesis of hepcidin, resulting in anemia of inflammation (AI). The serum hepcidin concentration in CHF patients with anemia was measured in order to better understand anemia in CHF. Serum hepcidin-25, erythropoietin (EPO), ferritin and IL-6 concentrations were measured in 61 CHF patients. Among these patients, 36 patients had anemia. A group of 16 patients without cardiac disease or anemia were recruited as controls. Serum IL-6 and EPO were higher and hepcidin-25 was lower in CHF patients with anemia than in controls. Hepcidin-25 correlated with EPO and ferritin but not with IL-6. Results of multivariable regression analysis showed that independent predictors of serum hepcidin-25 included EPO and ferritin but not IL-6. Serum hepcidin-25 concentrations were regulated by iron storage and erythropoiesis but not by IL-6 in CHF patients with anemia. These findings might indicate that AI is a minor cause of anemia in CHF.

Prevalence and Clinical Characteristics Associated with Anemia in Chronic Heart Failure in Argentina. A Report from Hospical II Registry

Prevalence and Clinical Characteristics Associated with Anemia in Chronic Heart Failure in Argentina. A Report from Hospical II Registry

Managing anaemia in chronic heart failure

Anaemia is common in chronic heart failure (CHF) and when present the individual is more debilitated and at an increased risk of death. The causes are complex and result in complicated pathophysiological processes which are difficult to manage. The development of anaemia in heart failure leads to a process of terminal decline. Therefore it is important that health care professionals dealing with these patients have an understanding of the aetiology and possible treatments. The purpose of this article is to provide an explanation of the causes of anaemia, and discuss treatment and management options based on clinical trials related to anaemia in chronic heart failure

Comorbidities in heart failure: a key issue

Comorbidities in heart failure: a key issue

Anemia in Chronic Heart Failure

Anemia is frequently observed in patients with chronic heart failure and is increasingly recognized as an important and treatable condition. The present review will summarize the current knowledge of the prevalence, causative factors, and pathophysiologic correlates of anemia in chronic heart failure. Despite increasing knowledge of anemia there are very few evidence-based recommendations for treatment. Potential benefits of therapy with supplemental hematinics such as iron, subcutaneous erythropoiesis-stimulating agents, or both will also be discussed.

Abstract 2361: Bone Marrow Dysfunction In Chronic Heart Failure Patients Contributes To Impaired Erythropoiesis

Background: We hypothesised that anemia in chronic heart failure (CHF) patients is caused by bone marrow dysfunction. Methods: Bone marrow was harvested during cardiac surgery from 17 patients with CHF (LVEF 32 ± 1.8 %) and 17 age matched control patients with normal cardiac function (LVEF ≥ 55%). Early hematopoietic progenitor cells (CD34 + ) and committed erythroid cells (CD71 bright ), apoptosis (Annexin-V + /DAPI + ) and EPO-receptor (EPO-R) density were quantified by FACS. Erythroid and myeloid colony formation of isolated CD34 + cells was assessed in methylcellulose containing incrementing doses of erythropoietin (EPO) or myeloid cytokines. After 14 days Burst Forming Units Erythroid (BFU-E) or granulocyte and monocyte colonies were quantified. Results: Patients with CHF had lower hemoglobin levels and 35% of CHF patients had anemia. The numbers of CD34 + and CD71 bright cells were 2 fold lower in CHF patients (P &lt; 0.05). Throughout the EPO dose-response range, CD34+ cells of CHF patients produced a 3-fold lower number of BFU-E colonies than controls (figure 1 , P &lt; 0.02). Concomittantly, myeloid colony formation was 2 fold lower in CHF patients as well (P &lt; 0.05). This was associated with markedly increased apoptosis (P &lt; 0.01), but equivalent EPO-receptor expression. Lower BFU-E numbers were independently associated with higher NTproBNP levels (R = − 0.5, P = 0.03). However, BFU-E formation was comparable in anemic and non-anemic CHF patients (P = 0.8). Conclusions : General bone marrow dysfunction in CHF patients contributes to impaired erythropoiesis. Although this might render patients more susceptible to anemia, it does not exclusively explain its occurrence. Impaired erythropoiesis in heart failure patients

Loop Diuretic as Bedside Tool for Detecting Dilutional Anemia in Patients with Chronic Heart Failure

Background: Anemia has been reported to be a frequent condition among patients (pts) with chronic heart failure (CHF). The pathogenesis of anemia in CHF is multifactorial. We evaluated the prevalence of hemodilution and its contribution to pathogenesis of anemia in hospitalized pts with advanced and mild-to-moderate CHF. Methods: We examined the 345 consecutive pts with CHF. The age of the study population was 70±11 years. Study pts were divided into two groups in relation to presence or absence of peripheral edema and hepatomegaly.

Anemia in chronic heart failure: etiology and treatment options

Anemia is common in patients with chronic heart failure, and is related to increased morbidity and mortality. The etiology of anemia in heart failure is complex and still not fully resolved. The review will describe current advances in the understanding of the pathophysiology of anemia and the potential therapeutic effects of recombinant human erythropoietin. Recent attempts to resolve the preponderant etiology of anemia in chronic heart failure have further defined its multifactorial nature. Impaired renal perfusion and function resulting in blunted erythropoietin production as well as impaired erythropoiesis in the bone marrow account for a vulnerable erythropoietic system. Moreover, fluid retention causes hemodilutional anemia. Correction of anemia with recombinant human erythropoietin seems feasible and is currently being evaluated in a phase 3 clinical trial. In addition, recombinant human erythropoietin improves cardiac function in chronic heart failure through the recruitment of endothelial progenitor cells and exerts cytoprotective effects during acute myocardial infarction. Although recombinant human erythropoietin shows great promise, we should not neglect other treatable causes of anemia. Although the etiology of anemia in chronic heart failure is clearly multifactorial, correction of anemia with recombinant human erythropoietin seems promising. In addition to correction of anemia, recombinant human erythropoietin might exert important protective and regenerative effects on the myocardium.

The prevalence of anemia in chronic heart failure and its impact on the clinical outcomes

This review article summarizes the current medical literature reporting on the prevalence and prognostic significance of anemia in patients with heart failure. Almost all currently available data indicate that anemia is common in heart failure populations, with the majority of studies indicating prevalence >20%. Anemia appears to be more highly prevalent in patients with advanced age, with more severe limitations in functional capacity, and with greater severity of co-morbid chronic kidney disease. In most reported studies anemia is an independent predictor of increased mortality risk and increased risk of hospitalization for heart failure. These data provide the rationale for interventional treatment trials to determine if anemia is in the causal pathway for disease progression and increased mortality risk in HF patients.

Negative impact of cardio-renal anaemia syndrome on beta-blocker tolerance and subsequent major adverse cardiac event in chronic heart failure

Background: Recent evidence has shown that comorbid renal insufficiency and anaemia in chronic heart failure were associated with poor prognosis. Although beta-blocker therapy has been widely accepted for the treatment of heart failure, effect of cardio-renal anaemia syndrome (CRAS) on beta-blocker tolerance has not been well documented.

Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure

Pro-inflammatory cytokine over-expression may be implicated to the pathogenesis of anemia in chronic heart failure (CHF) through the suppression of bone marrow erythropoiesis. Erythropoietin administration has anti-inflammatory and anti-apoptotic properties in experimental CHF models and improves exercise capacity in anemic CHF patients. The present study investigates the effects of recombinant human erythropoietin analogue darbepoetin-α on circulating pro-inflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with CHF and anemia. Forty-one CHF patients (NYHA class: II–III; left ventricular (LV) ejection fraction (EF) <40%; hemoglobin <12.5 g/dl; serum creatinine <2.5 mg/dl) were randomized to receive either 3-month darbepoietin-α at 1.5 μg/kg every 20 days plus iron orally ( n = 21) or placebo plus iron orally ( n = 20). LV systolic function, plasma B-type natriuretic peptide (BNP), inflammatory markers (TNF-α, IL-6, CRP), anti-inflammatory cytokine IL-10, endothelial adhesion molecules (soluble ICAM-1 and VCAM-1) and soluble apoptosis mediators (soluble Fas, soluble Fas ligand), and 6-min walking distance were assessed at baseline and 3 months post-treatment. In darbepoetin-α treated patients, plasma BNP (451 (62-2770) from 802 (476-4440) pg/ml, p = 0.002), IL-6 (6.5 ± 4.7 from 10.5 ± 7.8 pg/ml, p = 0.013) and soluble Fas ligand (53.2 ± 16.6 from 59.2 ± 17.9 pg/ml, p = 0.023) decreased significantly, while LVEF (32 ± 6 from 26 ± 6%, p < 0.001), hemoglobin (12.8 ± 1.4 from 10.9 ± 1.0 g/dl, p < 0.001) and 6-min walked distance (274 ± 97 from 201 ± 113 m, p < 0.01) increased significantly. No significant changes were observed in the placebo arm, except for a worsening in 6-min walked distance ( p = 0.044). In conclusion, darbepoetin-α reduces circulating pro-inflammatory cytokine IL-6 and apoptotic mediator soluble Fas ligand in CHF patients with anemia, with a parallel improvement of cardiac performance and exercise capacity.

Prognostic value of reduced kidney function and anemia in patients with chronic heart failure

The present study aimed to evaluate the prognostic value of B-type natriuretic peptide (N-proBNP), renal dysfunction and anemia in chronic heart failure (CHF) patients. We analyzed data from a prospective cohort of 153 patients (mean age 64 years) with CHF referred to our hospital center. Clinical, echocardiographic and laboratory data were drawn during hospital recovery in all patients. Kidney dysfunction was defined as a glomerular filtration rate (GFR) < 60 ml/min and anemia as a hematocrit < 35%. After discharge, patients attended the outpatient clinic of our institution. Kidney dysfunction was diagnosed in 37% of cases, whereas anemia was present in 25% of patients. During follow-up (median time 456 days), 32 patients died. Multivariate Cox proportional hazard model revealed that N-proBNP [hazard ratio (HR) = 1.002; P < 0.001] and GFR (HR = 0.972; P < 0.005) were significant predictors for mortality after adjustment for confounding variables. Kaplan-Maier analysis demonstrated a progressive decrease in survival from lowest to highest tertiles of N-proBNP values (log rank = 28.7; P < 0.001) and from higher to lower GFR values (log rank = 5.63; P < 0.01). Moreover, parametric survival analysis by the Weibull model demonstrated that the estimated probability of survival adjusted for N-proBNP values was higher in patients with GFR > or = 60 ml/min than in those with GFR < 60 ml/min (P < 0.001). Increased N-proBNP and decreased kidney function, but not anemia, are independent risk factors for mortality in patients with CHF.

Therapeutic potential of erythropoietin in cardiovascular disease: Erythropoiesis and beyond

Erythropoietin (EPO) is a glycoprotein hormone implicated in the regulation of red blood cell production. Anemia is common in chronic heart failure (CHF) patients and associated with an inappropriately low EPO-production, suggesting a role for its recombinant human form (rhEPO) in treatment. Although safety concerns have been raised regarding treatment with rhEPO in patients with chronic kidney disease, treatment with rhEPO in patients with CHF has so far been safe and well tolerated. The effect of rhEPO on outcome in anemic CHF patients is under investigation in a phase III clinical trial. In addition to its erythropoietic effects, EPO has been detected in the cardiovascular system, fueling intense research into possible non-hematopoietic effects. EPO has been shown to exert protective effects on the heart during acute myocardial ischemia and improve cardiac function in experimental CHF. Acute protection is mediated through reduction of apoptotic cell death. Improvement of cardiac function in CHF is related to myocardial neovascularization. EPO exhibits a vast array of beneficial effects in cardiovascular disease. In addition to the correction of anemia in CHF, rhEPO might benefit patients with cardiovascular disease.

Treatment of anaemia in chronic heart failure optimal approach still unclear

Anaemia, most commonly defined using the WHO definition as a haemoglobin < 13 g/dL in men and < 12.0 g/dL in women, has variable prevalence in heart failure. Rates vary between 4 and 55% dependent on the population studied and the definition of anaemia used.1,2 Anaemia is more common in patients with NHYA functional class III or IV symptoms and in those with renal dysfunction.1 The increasing interest in this subject reflects the observations that have been made regarding the independent clinical impact of low haemoglobin in heart failure. The presence of anaemia is associated with worse symptoms, reduced exercise capacity, and an increased risk of hospital admission. In addition, anaemia also portends a worse prognosis, with a 2–3% increased risk of death per 1% reduction in haematocrit.3 A number of factors contribute to the pathogenesis of anaemia in heart failure. Expansion of blood volume can result in haemodilution, producing ‘anaemia’ without a reduction in actual red cell volume. Other causes include renal dysfunction, and iron and other haematinic deficiencies. Angiotensin-converting enzyme inhibitors, commonly prescribed in heart failure patients, are also associated with a low haemoglobin possibly by suppressing erythropoietin production. In addition, proinflammatory cytokines such as interleukin-1 and -6 and tumour necrosis factor-α, significantly elevated in more severe forms of heart failure, can result in decreased erythropoietin production or, alternatively, resistance to the actions of erythropoietin. Finally, chronic gastrointestinal blood loss, made more likely as a result of antiplatelet and antithrombotic agents, can also contribute to anaemia in these patients. The association between anaemia and poorer outcome has led to the hypothesis that treating anaemia of no definable cause in heart failure may improve outlook. Two specific therapies have been considered, supplementing haematinics such as iron, and using subcutaneous erythropoiesis-stimulating agents … *Corresponding author. Tel: + 353 1 2845735; fax: + 353 1 2304639. E-mail address: kenneth.mcdonald{at}ucd.ie