Is Correction of Iron Deficiency a New Addition to the Treatment of the Heart Failure?

Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF patients). Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure.

Anemia and iron deficiency in COPD patients: prevalence and the effects of correction of the anemia with erythropoiesis stimulating agents and intravenous iron.

BACKGROUND: Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD). The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease. METHODS: (i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks. One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS). RESULTS: (i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission. Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured. All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients. Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment. There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014. CONCLUSIONS: ID is common in COPD patients but is rarely looked for or treated. Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea.

The role of iron, omega-3 Fatty acids, and vitamins in heart failure.

OPINION STATEMENT: The high prevalence of iron deficiency in heart failure (HF), its easy detection, and its rapid treatment effects with intravenous compounds including, among other things, improved New York Heart Association class, quality of life, and exercise capacity, may offer a major new addition to the treatment of HF. Although more research is required in HF, iron deficiency has been recognized as a disease for over a century and there is no question that its correction is desirable for improving the health and the quality of life of the iron-deficient patient. Iron deficiency with or without an associated anemia should be routinely searched for and treated in HF patients. Controlled studies of omega-3 fish oils suggest that they are cardioprotective in HF. They also may have additional value as safe and highly effective analgesics and anti-inflammatory agents in HF patients who often cannot take traditional nonsteroidal agents. The American Heart Association has recently recommended use of fish and/or fish supplements for all patients with cardiovascular disease. However, practical questions remain. For example, it is not clear what the optimal ratio of the two major components of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), should be in supplements. The role of other vitamins, such as vitamin D, in HF remains unclear.

The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome.

Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, cardiac and renal function, quality of life, exercise capacity and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage related to the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.

Intravenous iron in heart failure: beyond targeting anemia.

Iron deficiency is commonly seen in congestive heart failure (CHF) in both anemic and nonanemic patients. In six studies in which these iron-deficient patients with CHF were treated with intravenous (IV) iron, five found an improvement in the hemoglobin. In uncontrolled and controlled studies, the New York Heart Association (NYHA) class, quality of life, and exercise capacity were improved consistently with IV iron. In some studies, cardiac function also was improved. In one large, double-blind, placebo-controlled study of IV iron, the patient global assessment, quality of life, and NYHA class improved rapidly in both those who were anemic or not anemic. In contrast to these studies, another controlled study of anemia in CHF showed no effect of oral iron on hemoglobin or on any cardiac parameters over 1 year. These studies suggest that CHF in both anemic and nonanemic iron-deficient patients may benefit from a course of IV iron, but not oral iron.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

The anemia of heart failure.

Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of erythropoiesis-stimulating agents (ESA), such as EPO, as well as oral and, probably more importantly, intravenous (IV) iron. The many studies on anemia in CHF patients treated with ESA and oral or IV iron, and even with IV iron without ESA have up to now shown a quite consistent positive effect on hospitalization, fatigue, shortness of breath, quality of life, exercise capacity, and beta-natriuretic peptide reduction, in the absence of increased cardiovascular damage related to the therapy. Adequately powered long-term placebo-controlled studies of ESA and/or IV iron are currently being carried out and their results are eagerly awaited.

The role of correction of anaemia in patients with congestive heart failure: a short review.

Many patients with Congestive Heart Failure (CHF) are anaemic. This anaemia is associated with more severe CHF and a higher incidence of mortality, hospitalisation and morbidity. The only way to prove that the anaemia is causing this worsening of CHF is to correct it. We review here some of the published papers about correction of anaemia. Many studies show a positive effect of Erythropoietin (EPO) or its' derivatives when administered in combination with oral or IV iron, with improvements in left and right ventricular systolic and diastolic function, dilation and hypertrophy and renal function. In addition, a reduction in hospitalisations, diuretic dose, pulmonary artery pressure, plasma volume, heart rate, serum Brain Natriuretic Peptide levels, the inflammatory marker Interleukin 6, soluble Fas ligand--a mediator of apoptosis, and improvements in New York Heart Association class, exercise capacity, oxygen utilization, caloric intake, Quality of Life and the activity of Endothelial Progenitor Cells, have been observed. Iron deficiency may also play an important role in this anaemia, since improvements in CHF have also been reported following treatment with IV iron alone. However, until the ongoing large placebo-controlled studies of the EPO derivative darbepoetin or IV iron are completed, we will not know whether these treatments really influence CHF outcome.

Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency.

OBJECTIVES: Iron deficiency anemia is a frequent finding in many patients with congestive heart failure (CHF). The purpose of this study was to assess the effect of intravenous (i.v.) iron on the anemia of CHF patients and on cardiac remodeling, New York Heart Association (NYHA) classification and renal function. METHODS: Thirty-two patients with well-treated CHF which was NYHA class III-IV, and with hemoglobin (Hb) persistently <11 g/dL, were treated with i.v. iron over 26 weeks. Echocardiographic, hematological and renal parameters were measured at the beginning and end of the study. RESULTS: Hb increased significantly from 10.7 +/- 0.4 g/dL to 13.7 +/- 0.4 g/dL and from 9.4 +/- 0.6 g/dL to 12.7+/- 0.8 g/dL in the NYHA III and IV groups respectively. Posterior wall thickness, septal thickness (ST), left ventricular (LV) end diastolic volume and diameter, LV end systolic volume and diameter, LV mass index and LV ejection fraction (LVEF) were all abnormal initially. All of these parameters improved significantly in the NYHA III patients, and all but ST and LVEF improved significantly in the NYHA IV patients. NYHA classification improved from III to II in 9 of 19 NYHA III patients (47.4%) (p<0.01) but did not improve in any of the 13 NYHA IV patients. CONCLUSION: Intravenous iron causes a marked increase in hemoglobin in anemic CHF patients, and this is frequently associated with an improvement in cardiac remodeling and NYHA classification.

Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome.

BACKGROUND: Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its correction with erythropoietin (EPO) on cardiac structure and function. OBJECTIVES: The present study examines in patients with advanced CHF, chronic renal insufficiency, and anemia the effects of beta-EPO on left ventricular (LV) systolic diameter and volume (LVSD and LVSV), LV diastolic diameter and volume (LVDD and LVDV), LV mass, LV ejection fraction (LVEF), pulmonary artery pressure (PAP), and B-type natriuretic peptide (BNP) levels. METHODS: Fifty-one consecutive subjects affected with advanced CHF and anemia were studied. We performed a randomized double-blind controlled study of correction of anemia with subcutaneous EPO for 4 months (group A, 26 patients) using saline as the placebo in the control group (group B, 25 patients). We then maintained the EPO treatment in the treated group for another 8 months. Both groups received oral iron throughout the total 12-month period. Echocardiographic evaluation, BNP levels, and hematological parameters are reported at 4 and 12 months. RESULTS: The patients in group A during the double-blind phase (4 months) demonstrated an increase in LVEF and mild reduction in LVSD and LVSV with respect to baseline and to group B with no differences in PAP, LVDD, and LVDV. Over the 12-month period, the hemoglobin increased from 10.40.6 to 12.4 +/- 0.8 g/dL (P < .01) in group A but did not change in group B. Compared with group B, group A had lower LVDD, LVSD, LVDV, LVSV, LV mass, PAP, and BNP and higher LVEF. The serum creatinine and creatinine clearance remained unchanged in the 2 groups. CONCLUSIONS: In anemic patients with CHF, correction of anemia with EPO and oral iron over 1 year lead to an improvement in LV systolic function, LV remodeling, BNP levels, and PAP compared with a control group in which only oral iron was used.

Improvement of anemia with erythropoietin and intravenous iron reduces sleep-related breathing disorders and improves daytime sleepiness in anemic patients with congestive heart failure.

BACKGROUND: Central sleep apnea (CSA) (with or without Cheyne-Stokes breathing) or obstructive sleep apnea (OSA) are common in congestive heart failure (CHF). Correction of anemia may improve CHF. We hypothesized that correction of anemia might also improve sleep-related breathing disorders (SRBDs) in CHF. METHODS: Thirty-eight patients with CHF and anemia (hemoglobin level < 12 g/dL) were treated with erythropoietin and intravenous iron to a target hemoglobin level of 13 g/dL. Home sleep recordings were done before and after 3 months of treatment. RESULTS: Thirty-seven patients had SRBD (Apnea Hypopnea Index [AHI] of > or = 10). Hemoglobin level increased from 10.4 +/- 0.8 to 12.3 +/- 1.2 g/dL (P < .001). Total AHI values decreased from 35.9 +/- 12.2 to 24.9 +/- 12.2 (P < .001). The AHI of CSA, OSA and Cheyne-Stokes breathing decreased from 26.5 +/- 14.6 to 18.6 +/- 7.7, from 9.4 +/- 10.9 to 6.9 +/- 9.8, and from 13.1 +/- 16.4 to 9.0 +/- 12.2, respectively (all P < .05). Sleep minimal oxygen saturation (SaO2) increased from 62% +/- 12% to 71% +/- 11%; Epworth Sleepiness Scale score improved from 9.4 +/- 6.2 to 6.0 +/- 5.0 and New York Heart Association class improved from 2.9 +/- 0.4 to 1.7 +/- 0.7, all P < .001. Hemoglobin level improvement correlated with improvement in OSA+CSA, CSA, minimal SaO2, Epworth Sleepiness Scale score, and New York Heart Association class (all P < .001). CONCLUSION: Improvement of anemia in CHF is associated with a reduction in SRBD and an improvement in daytime sleepiness.

The interaction between heart failure and other heart diseases, renal failure, and anemia.

Anemia, defined as a hemoglobin level of less than 12 g/dL, often is seen in congestive heart failure (CHF). It is associated with an increased mortality and morbidity and increased hospitalizations. Compared with nonanemic patients the presence of anemia also is associated with worse cardiac clinical status, more severe systolic and diastolic dysfunction, a higher beta natriuretic peptide level, increased extracellular and plasma volume, a more rapid deterioration of renal function, a lower quality of life, and increased medical costs. The only way to determine if anemia is merely a marker for more severe CHF or actually is contributing to the worsening of the CHF is to correct the anemia and see if this favorably influences the CHF. In several controlled and uncontrolled studies, correction of the anemia with subcutaneous erythropoietin (EPO) or darbepoetin in conjunction with oral and intravenous iron has been associated with an improvement in clinical status, number of hospitalizations, cardiac and renal function, and quality of life. However, larger, randomized, double-blind, controlled studies still are needed to verify these initial observations. The effect of EPO may be related partly to its nonhematologic functions including neovascularization; prevention of apoptosis of endothelial, myocardial, cerebral, and renal cells; increase in endothelial progenitor cells; and anti-inflammatory and antioxidant effects. Anemia also may play a role in increasing cardiovascular morbidity in chronic kidney insufficiency, diabetes, renal transplantation, asymptomatic left ventricular dysfunction, left ventricular hypertrophy, acute coronary syndromes including myocardial infarction and chronic coronary heart disease, and in cardiac surgery. Again, controlled studies of correction of anemia are needed to assess its importance in these conditions. The anemia in CHF mainly is caused by a combination of renal failure and CHF-induced increased cytokine production, and these can both lead to reduced production of EPO, resistance of the bone marrow to EPO stimulation, and to cytokine-induced iron-deficiency anemia caused by reduced intestinal absorption of iron and reduced release of iron from iron stores. The use of angiotensin-converting enzyme inhibitor and angiotensin receptor blockers also may inhibit the bone marrow response to EPO. Hemodilution caused by CHF also may cause a low hemoglobin level. Renal failure, cardiac failure, and anemia therefore all interact to cause or worsen each other--the so-called cardio-renal-anemia syndrome. Adequate treatment of all 3 conditions will slow down the progression of both the CHF and the chronic kidney insufficiency.

Anemia, chronic renal disease and congestive heart failure--the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists.

Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, poor quality of life (QoL), progressive chronic kidney disease (CKD) which can lead to end stage kidney disease (ESKD), or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these people is the fact that they are often anemic. The anemia in CHF is due mainly to the frequently-associated CKD but also to the inhibitory effects of cytokines on erythropoietin production and on bone marrow activity, as well as to their interference with iron absorption from the gut and their inhibiting effect on the release of iron from iron stores. Anemia itself may further worsen cardiac and renal function and make the patients resistant to standard CHF therapy. Indeed anemia in CHF has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, the need for higher doses of diuretics, progressive worsening of renal function and reduced QoL. In both controlled and uncontrolled studies of CHF, the correction of the anemia with erythropoietin (EPO) and oral or intravenous (IV) iron has been associated with improvement in many cardiac and renal parameters and an increased QoL. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia--by reducing apoptosis of cardiac and endothelial cells, increasing the number of endothelial progenitor cells, and improving endothelial cell function and neovascularization of the heart. Anemia may also play a role in the worsening of acute myocardial infarction and chronic coronary heart disease (CHD) and in the cardiovascular complications of renal transplantation. Anemia, CHF and CKD interact as a vicious circle so as to cause or worsen each other- the so-called cardio renal anemia syndrome. Only adequate treatment of all three conditions can prevent the CHF and CKD from progressing.

Erythropoietin in heart failure.

The incidence of both congestive heart failure (CHF) and end-stage renal disease both are increasing. Anemia is common in both conditions and is associated with a marked increase in mortality and morbidity in both CHF and chronic kidney insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2. In other words, a vicious circle frequently is present in which CHF can cause or worsen both anemia and CKI, in which CKI can cause or worsen both anemia and CHF, and in which anemia can cause or worsen both CHF and CKI. We have called this vicious circle the cardio renal anemia syndrome. Optimal treatment of CHF with all the recommended CHF medications at their recommended doses will, in our experience, frequently fail to improve the CHF and CKI if anemia is present and is not corrected. On the other hand, correction of the anemia with subcutaneous erythropoietin and intravenous iron has caused a great improvement in the CHF including a marked improvement in patient and cardiac function and a marked reduction in the need for hospitalization and for high-dose diuretics. It also frequently has caused renal function to improve or at least stabilize. In addition, patients' quality of life and exercise capacity also have improved with the correction of the anemia. In CKI patients, anemia also may play an important role in increasing the risk for death, coronary heart disease, stroke, and progression to end-stage renal disease. Erythropoietin may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell apoptosis and by increasing neovascularization, both of which could prevent tissue damage. This could have profound therapeutic implications not only in CHF but in the future treatment of myocardial infarction, coronary heart disease, strokes, and renal failure.

Therapy insight: congestive heart failure, chronic kidney disease and anemia, the cardio-renal-anemia syndrome.

Congestive heart failure (CHF) and chronic kidney disease (CKD) often progress to end stage even with optimum medical therapy. One factor that is common to both conditions is anemia, which is present in about a third of CHF patients. CHF can cause or worsen both anemia and CKD, and CKD can cause or worsen both anemia and CHF. Thus, a vicious circle exists between these three conditions, with each causing or worsening the other. We have called this condition the cardio-renal-anemia syndrome. Anemia in CHF is associated with increased mortality and hospitalization, reduced cardiac function and evidence of more severe CHF and CKD than in nonanemic patients. Intervention studies in anemic CHF patients have shown that optimum medical treatment of CHF and the correction of the associated anemia with subcutaneous erythropoietin and oral iron or intravenous iron sucrose can improve cardiac function, patients' functional status, renal function and quality of life, and reduce the frequency of hospitalization and the dose of diuretics required.

Target Hemoglobin May Be Achieved with Intravenous Iron Alone in Anemic Patients with Cardiorenal Syndrome: An Observational Study.

BACKGROUND: The treatment of anemia in patients with cardiorenal syndrome (CRS) is based mainly on intravenous (IV) iron therapy and/or erythropoiesis-stimulating agents (ESAs). There are concerns about the safety of ESAs due to a potentially higher risk for stroke and malignancy. OBJECTIVE: We aimed to explore whether IV iron alone is sufficient to improve anemia in CRS patients and to define the predictors of treatment response. METHODS: We retrospectively analyzed data of 81 CRS patient treated for anemia at our clinic. All patients received IV iron for 6 weeks. A subset of patients was additionally given subcutaneous ESAs. The end point was the improvement from baseline in hemoglobin (Hb) and ferritin levels at week 7. RESULTS: We retrieved the files of 81 patients; 34 received IV iron alone and 47 were given IV iron and ESAs (the combination group). The Hb levels significantly increased in both groups (in the IV iron alone group: 10.6 ± 1.1 to 11.9 ±1.1 g/dl, p < 0.001; in the combination group: 10.2 ± 0.9 to 12.4 ± 1.3 g/dl, p < 0.001), but more pronouncedly in the combination group (2.17 vs. 1.24 g/dl; p = 0.001). The platelet count decreased significantly in the IV iron alone group but was unchanged in the combination group. Eighty percent of patients attained a Hb target of 11 g/dl, with no significant difference between the two groups (73.5 vs. 85.1%; p = 0.197). Low baseline Hb was the only predictor of a favorable outcome to treatment. CONCLUSION: Our observational study suggests that IV iron treatment without ESAs may substantially raise the Hb level to ≥11 g/dl in CRS patients. This treatment strategy may reduce the use of ESAs and hence its potential adverse effects.

The importance of anemia and its correction in the management of severe congestive heart failure.

About half of all the patients with CHF are anemic (they have a hemoglobin of < 12 g%). The prevalence and severity of this anemia increase with increasing severity of the CHF. The anemia is caused by a combination of poor nutrition, associated renal insufficiency causing inappropriately low Erythropoietin (EPO) levels, bone marrow depression and EPO resistance caused by excessive TNF alpha and other factors, gastrointestinal blood loss caused by aspirin, ACE inhibitors, EPO loss in the urine with proteinuria, and hemodilution caused by the excessive plasma volume. Studies have shown that the anemia is an independent risk factor for death in CHF, almost doubling the mortality rate. Correction of the anemia with subcutaneous EPO and IV iron improves cardiac function and functional capacity, helps prevent the progression of renal failure, markedly reduces hospitalization and diuretic doses, and improves self assessed quality of life. This so-called Cardio Renal Anemia Syndrome is very common in CHF. Its successful treatment demands close cooperation between cardiologists and nephrologists.