Search

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.

Introduction: Iron Deficiency (ID) is common in heart failure (HF), and is an independent contributor to mortality and morbidity. We examined whether patients with previously known HF who were recently hospitalized, had previous treatment for ID, were investigated for it at the time of hospitalization, and, if ID was found, were prescribed iron on discharge., Methods: We examined the records of 76 consecutive patients admitted to our hospital medical wards with a primary diagnosis of HF., Results: Anemia (Hb<12 g/dl) was found in 42/76 patients (55.3%). In 55/76 patients (72.4%) there was no iron workup, in 6 (7.9%) an incomplete iron workup with serum iron, transferrin or ferritin lacking and in 15/76 (19.7%) a complete iron workup. If ID was defined as either a serum ferritin of <100 μg/l or a serum ferritin of 100-299 μg/l and a %Transferrin Saturation of <20% it was found in 12/15 (80%) of those with a complete workup; in 9 of 10 (90%) of the anemic patients and in 3 of 5 (60%) of those non-anemic patients. At discharge 11/15 (73.3%) of those with a complete iron workup were given iron, 10 orally and 1 IV. In those 6 with an incomplete workup 2 were started on oral iron (33.3%) and in those without any workup, 1 of 55 (1.8%) was given oral iron., In Conclusions: ID is common in hospitalized HF patients but is usually not sought after by physicians at the time of admission. However if detected the physicians usually treated it., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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.

Anaemia is common in congestive heart failure (CHF) and is associated with increased mortality, morbidity and progressive renal failure. The common causes of the anaemia are the associated renal failure and excessive cytokine production, both of which can cause depression of the erythropoietin (EPO) production in the kidney and depression of EPO response in 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. Attempts to control this anaemia will have to consider the use of both erythropoiesis stimulating agents (ESA) as well as oral and, probably more importantly, intravenous (IV) iron. Studies of anaemia in CHF with ESA and oral or IV iron and even with IV iron alone have shown a positive effect on hospitalisation, fatigue and shortness of breath, 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 therapy. Although some studies and meta-analyses have revealed improvement in these parameters others have not. Adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are needed and are currently being carried out.

It has recently been recognized that many patients with congestive heart failure (CHF) are anemic. The anemia is very often associated with chronic kidney disease (CKD). The more severe the anemia the more severe the CHF, with higher mortality, morbidity, and hospitalization rate. The only way to prove that the anemia is itself a causative factor in the progression of both the CKD and the CHF is to correct it. In this paper we review the results of published papers and some preliminary reports about correction of this anemia in CHF. These studies frequently showed that erythropoietic stimulating agents (ESA) with oral or IV iron often resulted in improvement in left ventricular systolic and diastolic function, dilation, and hypertrophy, stabilization or improvement in renal function, reduced hospitalizations, diuretic dose, mitral regurgitation, pulmonary artery pressure, plasma volume, heart rate, serum brain natriuretic peptide levels, and the inflammatory markers C reactive protein and Interleukin 6, and an improvement in New York Heart Association class, exercise capacity, oxygen utilization during exercise, sleep apnea, caloric intake, depression, and quality of life. The activity of endothelial progenitor cells was also increased. Iron deficiency may also play an important role in the anemia, because significant improvement of cardiac, renal, and functional status in these anemic CKD-CHF has been seen after treatment with IV iron alone. Clearly more work is needed to clarify the relationship between anemia, CKD and CHF.

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., (Copyright 2009 S. Karger AG, Basel.)

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.

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.

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.

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.

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.

Anaemia is present in approximately 40% of cases of congestive heart failure (CHF) and is associated with a higher mortality, a lower left ventricular ejection fraction, a lower cardiac functional status, a higher rate of hospitalization, signs of malnutrition, a lower exercise capacity, a progressive fall in renal function, an increased need for high dose diuretics, hyponatraemia, an increased plasma volume, a reduced red cell volume and a lower quality of life. In both uncontrolled and controlled studies, correction of the anaemia with subcutaneous erythropoietin and, in some cases, with the addition of intravenous iron, has been shown to improve these parameters. A vicious circle is present between CHF, chronic kidney insufficiency (CKI) and anaemia, each capable of causing or being caused by the other, the so-called cardio renal syndrome. If larger randomized, controlled, double-blind studies confirm these observations, correction of the anaemia may prove to be a useful addition to the prevention and progression of both CHF and CKI. Cooperation between nephrologists, cardiologists and other internists to identify and treat these anaemic CHF patients early will help prevent progression of both the cardiac and renal disease.

Unlabelled: Anaemia is frequently found in patients with chronic heart failure (CHF) and has been associated with an increase in mortality and morbidity, impaired cardiac and renal function and a reduced quality of life (QoL) compared with non-anaemic CHF patients. Correction of anaemia with recombinant human erythropoietin (epoetin) has been associated with an improvement in CHF in both controlled and uncontrolled studies. The present study describes our findings in a series of 78 consecutive patients with symptomatic CHF and anaemia (haemoglobin (Hb) level <12.0 g/dl) treated with epoetin beta and, if necessary, intravenous iron sucrose. Over a mean observation period of 20.7 +/- 12.1 months, mean Hb levels increased from 10.2 +/- 1.1 to 13.5 +/- 1.2 g/dl, p < 0.01. New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) were significantly improved and the number of hospitalizations was significantly reduced with the period before treatment (all p < 0.01). Serum creatinine and creatinine clearance (CCr) were 2.2 +/- 0.9 mg/dl and 32.5 +/- 26.5 ml/min, respectively, at baseline, and remained stable over the observation period. Interestingly, >90% of the patients had concomitant mild-to-moderate chronic kidney disease at baseline and study end (CKD), as defined by the accepted diagnostic criterion of a CCr <60 ml/min., Conclusions: The correction of the anaemia with epoetin beta together with initial intravenous iron supplementation, resulted in significant improvements in NYHA class and cardiac function, and a reduction in hospitalization rate. Moreover, renal function was maintained stable in most patients.

Objectives: To find the prevalence of anemia in patients hospitalized with the primary diagnosis of congestive heart failure (CHF)., Background: There is growing evidence that anemia is common in CHF and may contribute to the high morbidity and mortality associated with this condition. However, there is considerable disagreement about the prevalence of anemia in this condition., Methods: In 338 consecutive patients who were admitted to the medical wards with a primary diagnosis of CHF we extracted from the charts the hemoglobin (Hb), serum creatinine, age, sex, New York Heart Association (NYHA) functional class, presence of smoking, diabetes, hypertension, hyperlipidemia and the primary cardiac etiology of the CHF. Anemia was considered to be present when the Hb on admission was <12 g/dl., Results: All the patients were NYHA functional class III-IV. One hundred seventy seven (52.4%) of the 338 patients had a Hb on admission that was <12 g/dl. The mean Hb for the entire group was 12.0+/-1.8 g/dl. One hundred three (51.0%) of the 202 males were anemic compared to 74 (54.4%) of the 136 women. The mean serum creatinine was 1.7+/-1.1 mg/dl. The prevalence of renal insufficiency (serum creatinine >1.5 mg%) was 47.6%. There was a negative correlation between the level of serum creatinine and Hb (r=-0.294) P<0.00001. Of the 177 patients who were anemic, most of 114 (64.4%) had a serum creatinine >1.5 mg/dl., Conclusions: Anemia is a common finding in patients hospitalized with CHF and most anemic CHF patients have some degree of renal insufficiency. In view of the negative effect of anemia on cardiac function, it may be a common and important contributor to the mortality and morbidity of CHF in these patients.

Purpose of Review: Recent findings on the relationship between congestive heart failure and renal failure are summarized in this review., Recent Findings: Congestive heart failure is found in about one-quarter of cases of chronic kidney disease. The most common cause of congestive heart failure is ischemic heart disease. The prevalence of congestive heart failure increases greatly as the patient's renal function deteriorates, and, at end-stage renal disease, can reach 65-70%. There is mounting evidence that chronic kidney disease itself is a major contributor to severe cardiac damage and, conversely, that congestive heart failure is a major cause of progressive chronic kidney disease. Uncontrolled congestive heart failure is often associated with a rapid fall in renal function and adequate control of congestive heart failure can prevent this. The opposite is also true: treatment of chronic kidney disease can prevent congestive heart failure. There is new evidence showing the cardioprotective effect of carvedilol in patients on dialysis, and of simvastatin and eplerenone in patients with congestive heart failure. Use of non-steroidal anti-inflammatory drugs doubles the rate of hospitalization in patients with congestive heart failure. Anemia has been found in one-third to half the cases of congestive heart failure, and may be caused not only by chronic kidney disease but by the congestive heart failure itself. The anemia is associated with worsening cardiac and renal status and often with signs of malnutrition. Control of the anemia and aggressive use of the recommended medication for congestive heart failure may improve the cardiac function, patient function and exercise capacity, stabilize the renal function, reduce hospitalization and improve quality of life. Congestive heart failure, chronic kidney disease and anemia therefore appear to act together in a vicious circle in which each condition causes or exacerbates the other. Both congestive heart failure and anemia are often undertreated. Cooperation between nephrologists and other physicians in the treatment of patients with anemic congestive heart failure may improve the quality of care and the subsequent prognosis for both congestive heart failure and chronic kidney disease., Summary: Adequate and early detection and aggressive treatment of congestive heart failure and chronic kidney disease and the associated anemia may markedly slow the progression of both diseases.

Background: Many patients with congestive heart failure (CHF) have chronic kidney insufficiency (CKI) and anemia., Aims: The purpose of this review is to clarify the relationship between these three factors and to study the effect of correction of anemia in CHF and CKI., Findings: Anemia, CHF and CKI are each capable of causing or worsening each other. Thus they form a vicious circle which can result in progressive CHF, CKI and anemia. Aggressive therapy of CHF, CKI and control of the associated anemia with erythropoietin and i.v. iron can prevent the progression of CHF and CKI, reduce hospitalization, and improve quality of life., Conclusion: CHF patients are a major source of end-stage renal failure patients and deserve special attention. If treated well and early, progressive heart failure and renal failure can be prevented. Cooperation between nephrologists, cardiologists, and other internists will improve the care of all three conditions and prevent their progression., (Copyright 2004 S. Karger AG, Basel)

Background: Up to 64% of patients referred to nephrologists with chronic kidney insufficiency (CKI) have evidence of congestive heart failure (CHF), and most of these patients are also anemic. We have called this triad of anemia, CKI, and CHF the cardio renal anemia (CRA) syndrome. The 3 components of this syndrome form a vicious circle, with each one capable of causing or worsening the other 2. Anemia is found in one-third to one-half of CHF patients and can either cause or worsen the CHF, and can increase the mortality, hospitalization, and malnutrition in this condition. Anemia is also associated with a worsening of renal function in CHF and CKI, causing a more rapid progression to dialysis than is found in those without anemia. Uncontrolled CHF can cause rapid deterioration of renal function and may also cause anemia. Chronic kidney insufficiency can cause anemia and worsen the CHF., Methods: Aggressive therapy of CHF with all the accepted CHF medications in the accepted doses will often fail to improve the CHF if anemia is also present but is not corrected. However, when the anemia was corrected with subcutaneous erythropoietin and, in some cases, with intravenous iron, the cardiac and patient function and quality of life improved, the need for hospitalization and for high-dose oral and intravenous diuretics was strikingly reduced, and renal function, which had previously been deteriorating, stabilized., Results: Nephrologists should carefully assess the cardiac status of all CKI patients, including routinely getting an echocardiogram and possibly measuring B-type natriuretic peptide. Where CHF is present, the indicated CHF agents in the indicated doses should be used., Conclusion: Studies show that most cardiologists and internists do not recognize, investigate, or treat the anemia frequently seen in their CHF patients. In our experience cooperation between nephrologists and these specialists has increased their awareness about anemia, resulting in its earlier correction, and thus preventing the deterioration of the CHF, the CKI, and the anemia itself.

Background: Congestive heart failure is extremely common in octogenarians and is associated with severe fatigue, shortness of breath, recurrent hospitalizations, and death. These patients, many of whom are anemic, are often resistant to standard CHF therapy including angiotensin-converting enzyme inhibitors, beta-blockers and diuretics., Objectives: To examine whether correction of the anemia (hemoglobin < 12 g/dl) in CHF patients can improve their clinical condition., Methods: Forty octogenarians with anemia and severe resistant CHF were administered a combination of subcutaneous erythropoietin and intravenous iron sucrose., Results: This combination therapy led to a marked improvement in cardiac function, shortness of breath and fatigue, a marked reduction in the rate of hospitalization and a stabilizing of renal function., Conclusion: Anemia appears to be an important but ignored contributor to the progression of CHF, and its correction may improve cardiac and renal status as well as the quality of life in elderly patients.

Objective: To describe neuroendocrine responses that develop in dogs subjected to prolonged periods of ventricular pacing., Animals: 14 adult male hound-type dogs., Procedure: Samples were obtained and neuroendocrine responses measured before (baseline) and after 3 periods of ventricular pacing. A pacemaker was used to induce heart rates of 180, 200, and 220 beats/min (BPM). Each heart rate was maintained for 3 weeks before increasing to the next rate. Atrial natriuretic peptide, antidiuretic hormone, aldosterone, norepinephrine, epinephrine, and dopamine concentrations and plasma renin activity were measured. Severity of left ventricular compromise was estimated., Results: Shortening fraction decreased significantly with increasing heart rates (mean +/- SE, 35.5 +/- 1.4, 25.0 +/- 1.4, 19.5 +/- 1.9, and 12.2 +/- 2.3 for baseline, 180 BPM, 200 BPM, and 220 BPM, respectively). Atrial natriuretic peptide concentrations increased significantly at 180 BPM (44.1 +/- 3.0 pg/mL) and 200 BPM (54.8 +/- 5.5 pg/mL), compared with baseline concentration (36.8 +/- 2.6 pg/mL). Dopamine concentration increased significantly at 200 BPM (70.4 +/- 10.4 pg/mL), compared with baseline concentration (44.2 73 pg/mL). Norepinephrine concentrations increased significantly from baseline concentration (451 +/- 46.2 pg/mL) to 678 +/- 69.8, 856 +/- 99.6, and 1,003 +/- 2676 pg/mL at 180, 200, and 220 BPM, respectively., Conclusions and Clinical Relevance: Dogs subjected to ventricular pacing for 9 weeks developed neuroendocrine responses similar to those that develop in humans with more chronic heart failure and, except for epinephrine concentrations, similar to those for dogs subjected to ventricular pacing for < 6 weeks.

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia.

Objectives: This is a randomized controlled study of anemic patients with severe congestive heart failure (CHF) to assess the effect of correction of the anemia on cardiac and renal function and hospitalization., Background: Although mild anemia occurs frequently in patients with CHF, there is very little information about the effect of correcting it with erythropoietin (EPO) and intravenous iron., Methods: Thirty-two patients with moderate to severe CHF (New York Heart Association [NYHA] class III to IV) who had a left ventricular ejection fraction (LVEF) of < or =40% despite maximally tolerated doses of CHF medications and whose hemoglobin (Hb) levels were persistently between 10.0 and 11.5 g% were randomized into two groups. Group A (16 patients) received subcutaneous EPO and IV iron to increase the level of Hb to at least 12.5 g%. In Group B (16 patients) the anemia was not treated. The doses of all the CHF medications were maintained at the maximally tolerated levels except for oral and intravenous (IV) furosemide, whose doses were increased or decreased according to the clinical need., Results: Over a mean of 8.2+/-2.6 months, four patients in Group B and none in Group A died of CHF-related illnesses. The mean NYHA class improved by 42.1% in A and worsened by 11.4% in B. The LVEF increased by 5.5% in A and decreased by 5.4% in B. The serum creatinine did not change in A and increased by 28.6% in B. The need for oral and IV furosemide decreased by 51.3% and 91.3% respectively in A and increased by 28.5% and 28.0% respectively in B. The number of days spent in hospital compared with the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B., Conclusions: When anemia in CHF is treated with EPO and IV iron, a marked improvement in cardiac and patient function is seen, associated with less hospitalization and renal impairment and less need for diuretics.

The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.

Objectives: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization., Background: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown., Methods: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period., Results: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment., Conclusions: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

This study assessed the usefulness of the oral captopril test in the prediction of renal impairment among elderly patients with congestive heart failure (CHF). Forty-seven patients aged > or = 65 years with CHF (EF < 40%) participated in a prospective nonrandomized series. Blood samples for plasma renin activity (PRA) were drawn before and 60 minutes after 50 mg of oral captopril. Twenty-four hours later, captopril was administered (up to 75 mg/day over a 4 day period), and renal laboratory and clinical assessment were performed at baseline and for a 9 day period. In 7 of 47 patients (14.9%), deterioration of renal function was observed. During the captopril test, the PRA increased significantly after 1 hour in almost all patients and the mean blood pressure decreased from 99.2 +/- 14.6 mmHg to 92.2 +/- 13.7 mmHg (p < 0.001). All patients whose baseline PRA level was < 1.9 ng/ml/hr and whose stimulated PRA was < 3.2 ng/ml/hr maintained a stable renal function throughout the study period. Significant statistical correlation (p < 0.05) was found between the initial PRA, the changes in PRA or mean blood pressure during the captopril test, and the change in plasma creatinine and creatinine clearance in the entire group, and was even more evident in a subgroup of patients with an ejection fraction > or = 30%. All these correlations were not statistically significant in the patients with an ejection fraction < 30%. It is thus concluded that measurement of pretreatment PRA levels might be a useful laboratory tool for predicting the renal safety of captopril use in patients with CHF whose EF > or = 30%.

The purpose of this study was to examine the impact of intensive home-care surveillance on morbidity rates of elderly patients with severe congestive heart failure. Forty-two patients aged 78 +/- 8 years who had severe congestive heart failure (New York Heart Association functional classes III through IV, mean ejection fraction 27% +/- 6%), were examined at least once a week at home by internists from the district hospital and by a trained paramedical team. The year before entry to the home-care program was compared to the first year of home surveillance. The mean total hospitalization (hosp) rate was reduced from 3.2 +/- 1.5 hosp/yr to 1.2 +/- 1.6 hosp/yr and duration from 26 +/- 14 days/yr to 6 +/- 7 days/yr (p < 0.001 for both). Cardiovascular admissions decreased from 2.9 +/- 1.5 hosp/yr to 0.8 +/- 1.1 hosp/yr and duration from 23 +/- 13 days/yr to 4 +/- 4 days/yr (p < 0.001). The vital status (ability to perform daily activities, expressed in a 1 to 4 scale) was improved from 1.4 +/- 0.9 to 2.3 +/- 0.7 (p < 0.001). In conclusion, an intensive home-care program was associated with a marked decrease in the need for hospitalization and improved the functional status of elderly patients with severe congestive heart failure. Such a service might also have a cost-effective advantage and a major impact on health expenditure.

Background: Extranodal malignant lymphomas (ML) are known to occur with increased frequency in patients with human immunodeficiency virus infection. The authors report a 30-year-old man with acquired immune deficiency syndrome (AIDS) with ML primarily involving the heart and compare the clinical and pathologic features to those of previously reported patients., Methods: The patient's hospital record was reviewed and pertinent clinical data were abstracted. Tissue obtained at autopsy was processed for routine light microscopic study and immunohistochemistry. A computer-assisted search of the medical literature for patients with malignant cardiac lymphoma was performed., Results: The patient's initial signs and symptoms were nonspecific, and an abnormal gallium scan suggested pericarditis. Clinically, the course was characterized by progressive heart failure. Autopsy disclosed a diffuse large cell non-Hodgkin lymphoma of B-cell phenotype with massive involvement of the pericardium and extension into the myocardium. A literature search revealed 22 patients with cardiac lymphoma associated with AIDS. Clinical findings were nonspecific, but rapid progression of cardiac dysfunction was common after symptoms appeared. Pathologically, most lymphomas were of diffuse aggressive subtypes., Conclusions: ML of the heart is extremely rare but is being encountered with increasing frequency in patients with AIDS. The diagnosis should be considered in such patients in whom cardiovascular symptoms develop suddenly and progress rapidly.

Captopril and aspirin have been claimed to adversely affect renal function. This study was designed to evaluate the safety of concomitant administration of both drugs in patients with moderate to severe congestive heart failure (CHF). The study group consisted of 10 patients with a mean age of 77.6 +/- 4.4 years and a mean New York Heart Association functional class of 2.6 +/- 0.5. Captopril was administered in a rapidly escalating dose regimen over a 4-day period to a maximum dose of 75 mg/day. Aspirin 0.25 g/day was added from day 5 on. Renal plasma flow (RPF) was measured by iodohippurate scan and the creatinine clearance test (Ccr) was used as an index of glomerular filtration rate (GFR). Both Ccr and RPF remained unchanged throughout the study period; 48.9 +/- 16; 48.2 +/- 16.5; 49.4 +/- 16, and 222 +/- 67, 241 +/- 97, 237 +/- 88 ml/min, for days 0, 4, 9, respectively. Only 1 patient developed a significant decrease in Ccr following the administration of captopril. This patient had a further decrease when aspirin was added. The decrease in Ccr was accompanied by a marked reduction in filtration fraction and in mean arterial pressure. Our data suggest that the administration of aspirin to elderly patients with moderate CHF treated with captopril is relatively safe and is not associated with further deterioration in renal function.

We evaluated the safety of enalapril administration in 20 very old (76 +/- 7 years) patients with rapidly progressive congestive heart failure (deteriorating from New York Heart Association class 2 to class 4 on admission). They were all given increasing doses of enalapril regardless of concomitant diuretic therapy and state of hydration. Renal function deteriorated in four patients (group A) and remained unchanged in 16 (group B). The mean pretreatment serum creatinine level in group A was significantly higher than that in group B (2.4 vs 1.3 mg/dl, p less than 0.001). No patient with a serum creatinine level less than 1.9 mg/dl on admission had further impairment of renal function. Groups A and B did not differ by age, concomitant diseases (including hypertension and diabetes mellitus), or medications (including diuretics) or by in-hospital serum electrolyte concentrations and blood pressure. Renal damage was noted during the initial four days of the study and was reversible following discontinuation of enalapril. Our data suggest that enalapril can be safely administered to very old patients with rapidly progressive congestive heart failure provided that the initial serum creatinine level is below 1.9 mg/dl. In patients with a higher serum creatinine level, careful monitoring and prompt discontinuation of enalapril administration can prevent irreversible renal damage.

The effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect (VSD) is controversial. Nineteen infants with symptoms of congestive heart failure due to a VSD were studied with load-independent indexes during 4 study periods: (1) before any medication; (2) while on chronic diuretics; (3) while on both diuretics and digoxin; and (4) while on diuretics alone, to determine if digoxin: (a) increases "contractility" when added to diuretic therapy; and (b) improves symptoms. Symptoms, signs (heart and respiratory rates, and weight gain), shortening fraction, preload (left ventricular end-diastolic dimension), afterload (left ventricular end-systolic wall stress) and contractility were measured at each period. The difference between the measured and predicted velocities of circumferential fiber shortening for the measured left ventricular end-systolic wall stress served as an index of contractility. Eighteen infants also underwent catheterization. Mean pulmonary-to-systemic blood flow ratio was 3:1. When digoxin was added to diuretics, contractility index was significantly greater than in control subjects (0.13 +/- 0.15 vs 0.0 +/- 0.12 circ/s, p = 0.04). When patients were again on diuretics alone (after discontinuation of digoxin), contractility index was no longer different. Symptoms and signs were not significantly improved by either diuretics or digoxin. It is concluded that in infants with a large left-to-right VSD shunt and receiving digoxin and diuretics, contractility index was significantly greater than in control subjects. However, neither diuretics alone nor in combination with digoxin improved symptoms significantly.

To characterize the sympathetic nervous system response to congestive heart failure (CHF) in infants and children, plasma catecholamine levels were measured in 102 subjects undergoing routine cardiac catheterization (mean age 3.3 years, range 0.1 to 14.7), including 61 with left-to-right shunts. Plasma norepinephrine levels were significantly higher (p less than 0.0001) in children with CHF than in those without CHF. A highly significant association (p less than 0.0001) was found between the level of plasma norepinephrine and severity of CHF symptoms. This relation was found for CHF secondary to lesions producing a left-to-right shunt and CHF resulting from primary myocardial dysfunction. In congenital lesions with a left-to-right shunt, plasma norepinephrine levels correlated well with size of the shunt (Qp/Qs) (r = 0.75, p less than 0.001) and degree of pulmonary arterial hypertension (r = 0.70, p less than 0.001). Elevation of plasma norepinephrine concentrations in infants and children are seen with severe CHF regardless of its origin.

The maximal exercise capacity of patients with chronic heart failure is frequently reduced. To investigate whether this exercise intolerance is caused by inadequate nutritive flow to skeletal muscle, we compared cardiac outputs, leg blood flow, and leg metabolism during maximal bicycle exercise in seven patients with normal maximal oxygen uptake (VO2) (greater than 20 ml/min/kg; group A), eight patients with heart failure and moderately reduced maximal VO2 (15 to 18 ml/min/kg; group B), and eight patients with heart failure and markedly reduced maximal VO2 (less than 14 ml/min/kg; group C). As the severity of exercise intolerance increased from group A to group C there was a progressive decline in cardiac output and leg blood flow at any given workload accompanied by a progressive decline in maximal cardiac output (liters/min) (A, 12.4 +/- 1.0; B, 8.7 +/- 0.9; C, 5.5 +/- 0.7), maximal leg flow (liters/min) (A, 4.0 +/- 0.3; B, 2.6 +/- 0.4; C, 1.4 +/- 0.2), and maximal leg VO2 (ml/min) (A, 564 +/- 49; B, 403 +/- 41; C, 213 +/- 35 ml/min). All patients terminated exercise because of severe leg fatigue. At termination of exercise, all three groups exhibited similar marked levels of leg O2 extraction (%) (A, 80 +/- 2; B, 83 +/- 3; C, 89 +/- 1) and high femoral-arterial lactate gradients (mg/dl) (A, 15.4 +/- 2.6; B, 18.3 +/- 3.5; C, 19.2 +/- 3.6), suggesting that exercise was limited when a critical level of muscle underperfusion was reached. These data suggest that the reduced maximal exercise capacity of patients with chronic heart failure is primarily due to impaired nutritive flow to skeletal muscle and resultant muscular fatigue.

Vasodilators with different sites of action are used for long-term therapy of congestive heart failure, and selection of agents based on acute hemodynamic effects has been recommended. We compared the acute hemodynamic effects (by Swan-Ganz catheterization) and long-term responses (maximal oxygen uptake during exercise) associated with isosorbide dinitrate, a predominant venodilator, captopril, an arterial and venous dilator, and minoxidil, an arterial dilator, in 22 patients with congestive heart failure. In eight patients isosorbide dinitrate reduced pulmonary wedge pressure by 29% +/- 8% acutely (p less than .001) without significantly changing cardiac index or systemic vascular resistance. In eight patients captopril acutely reduced pulmonary wedge pressure by 42% +/- 22% (p less than .001) and systemic vascular resistance by 27% +/- 12% (p less than .01), while raising cardiac index by 19% +/- 18% (p less than .02). In six patients minoxidil raised cardiac index acutely by 38% +/- 30% (p less than .05) and reduced systemic vascular resistance by 35% +/- 12% (p less than .05) without changing pulmonary wedge pressure. After 2-5 months vasodilator administration maximal exercise oxygen uptake was increased by 7 +/- 3 ml/min/kg on isosorbide dinitrate (p less than .01), by 3 +/- 2 ml/min/kg on captopril (p less than .01), and by only 1 +/- 2 ml/min/kg on minoxidil (ns). Thus exercise capacity improved only during administration of drugs with venodilating action, failing to change during treatment with the arterial dilator despite a reduction in systemic vascular resistance. Predominantly arterial dilators alone may not be suitable for long-term vasodilator therapy for heart failure, and the regimens used should include venodilating agents.

The pathophysiologic role of high levels of circulating catecholamines in patients with congestive heart failure remains unclear. To assess the hemodynamic contribution of circulating catecholamines, metyrosine (alpha-methyl-p-tyrosine), an inhibitor of catecholamine synthesis, was administered to nine patients with acutely decompensated chronic congestive heart failure. Baseline left ventricular ejection fraction averaged 23.3 +/- 9.9%, whereas cardiac output averaged 3.69 +/- 1.03 liters/min, with a pulmonary wedge pressure of 27.4 +/- 8.5 mm Hg. After 48 h of metyrosine administration, plasma norepinephrine concentration decreased from 919.4 +/- 810.6 to 335.4 +/- 143.1 pg/ml (p less than 0.05). Plasma epinephrine concentration averaged 176.4 +/- 166.0 pg/ml at baseline, and was unchanged during metyrosine administration. Despite the significant decrease in circulating norepinephrine, no significant hemodynamic changes were observed during metyrosine administration. These results suggest that high levels of circulating norepinephrine may be more a marker of severe congestive heart failure than an important contributor to the underlying pathophysiology at this advanced stage of the disease process.

The cause of exercise intolerance in congestive heart failure is unclear. Hemodynamic and ventilatory responses were measured during symptomatic maximal upright bicycle exercise in 28 patients with chronic severe left ventricular failure who achieved a maximal oxygen uptake of only 12 +/- 4 ml/min/kg (+/- standard deviation). All patients reached anaerobic metabolism as the respiratory exchange ratio rose and arterial pH fell significantly. Pulmonary capillary wedge pressure increased from 20 +/- 10 mm Hg at rest to 38 +/- 9 mm Hg at peak exercise and cardiac index increased from 2.51 +/- 0.73 to 4.54 +/- 1.65 liters/min/m2 (both p less than 0.001). Systemic vascular resistance decreased, but pulmonary vascular resistance did not change during exercise. Despite the marked pulmonary venous hypertension at peak exercise, blood gases were unchanged (PaO2, 96 +/- 15 mm Hg; PaCO2, 35 +/- 7 mm Hg). Systemic arterial oxygen content increased from 16 +/- 2 to 17 +/- 2 vol% (p less than 0.01). Changes in pulmonary capillary wedge pressure did not correlate with changes in arterial oxygen content. Results were similar whether patients were limited by dyspnea or fatigue. Thus, exercise intolerance in patients with severe left ventricular failure is associated with marked elevation of pulmonary capillary wedge pressure and anaerobic metabolism without hypoxemia or altered carbon dioxide tension. These findings suggest that exercise ability in congestive heart failure is more dependent on cardiac output than on ventilatory consequences of pulmonary congestion.