European Journal of Heart Failure

European Journal of Heart Failure 2002 4(6):681-686; doi:10.1016/S1388-9842(02)00115-0

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© 2002 European Society of Cardiology

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

Donald S. Silverberg^a,*, Dov Wexler^b and Adrian Iaina^a

^a Department of Nephrology, Tel Aviv Medical Center Weizman 6, Tel Aviv 64239, Israel
^b Department of Cardiology and Congestive Heart Failure Out Patient Unit, Tel Aviv Medical Center Weizman 6, Tel Aviv 64239, Israel

^* Corresponding author. Tel.: +972-3-6973270; fax: +972-3-5469825. E-mail address: donald{at}netvision.net.il

	Abstract

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
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.

Key Words: Anemia • Renal failure • Congestive heart failure • Erythropoietin • Iron

Received August 17, 2001; Revised December 10, 2001; Accepted February 22, 2002

	1. Anemia and congestive heart failure (CHF)

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Anemia is known to cause CHF even in people with no underlying heart disease, and correction of the anemia with transfusions can correct the CHF [1]. What is less appreciated is that many CHF patients are frequently anemic [2,3], that the CHF itself may contribute to the production of the anemia [4] and that treatment of this anemia may greatly improve the status of these CHF patients [2]. Thus it is possible that in CHF a vicious circle is set in motion wherein CHF causes anemia and the anemia then worsens the CHF. Perhaps one reason for the high mortality, morbidity and high rate of re-hospitalization seen in CHF is that the associated anemia is not corrected.

	2. Why should CHF patients become anemic?

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
The anemia of CHF could be due to several factors [2]:

1. Iron deficiency caused by poor intake, malabsorption or chronic blood loss from, for example, use of prophylactic aspirin.
   
2. Anemia of chronic renal failure (CRF). CRF is frequently seen in CHF [5]. The anemia of CRF is due to a combination of many factors of which the most important is the reduced production of erythropoietin (EPO) in the kidney [5].
   
3. Loss of EPO and transferrin in the urine. Proteinuria is often seen in CHF [6] and it may cause the loss of EPO in the urine [7]. It may also cause loss of transferrin which can lead to iron deficiency anemia [7].
   
4. Use of angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors, especially in high doses, may interfere with both EPO production in the kidney and EPO activity in the bone marrow [8].
   
5. Increased activity of cytokines such as tumor necrosis factor (TNF) alpha. TNF alpha is very elevated in CHF [9] and has been shown to interfere with EPO production in the kidney, the erythropoietic response to EPO in the bone marrow [4,10], and with the release of iron from the reticulo-endothelial system for use in the production of red cells in the bone marrow [10]. The resistance to EPO in the bone marrow may explain why anemia can be present in CHF even when the levels of EPO in the serum are elevated, as they frequently are, in CHF [11].
   
6. Hemodilution. The increased plasma volume in CHF may cause a reduced Hb [1].
   

	3. How common is anemia in CHF?

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Many studies of CHF have shown that the mean hemoglobin (Hb) in patients is approximately 12 g% [2,3]. Since the lower limit of normal (the 95th percentile) for Hb for men is 13.5 g% and for women is 12 g% [12], this would suggest that at least one-half of the patients with CHF are anemic. In a study of 142 consecutive cases of CHF seen in our special CHF out-patient clinic [2] we found that the mean Hb was 11.9 g% and 55% of patients had a Hb less that 12 g% [2]. The prevalence and severity of the anemia increased with increased severity of the CHF. The mean Hb fell from 13.6 g% in New York Heart Association (NYHA) Class I to 10.9 g% in NYHA 4. The percentage of patients with anemia (Hb<12 g%) was 9.1%, 19.2%, 52.6% and 79.1% for NYHA class 1–4, respectively. Almost identical findings were recently found in CHF patients in the UK [13]. In our study, anemic, resistant CHF patients, who did not respond to maximally tolerated CHF medication, had an even lower mean Hb, 10.2 g% [2].

	4. How can anemia cause CHF?

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Anemia of any cause may produce CHF in the following manner [1]. Vasodilatation caused by the accompanying tissue hypoxia lowers the blood pressure thus activating the sympathetic nervous system (SNS). This causes peripheral vasoconstriction and tachycardia which are needed to maintain the blood pressure. The associated renal vasoconstriction activates the renin angiotensin aldosterone system (RAAS). The high angiotensin II levels further increase renal and peripheral vasoconstriction and increase aldosterone production. The resultant reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) can cause renal ischemia and fluid retention. The renal insufficiency thus produced may also cause anemia through reduced EPO production and bone marrow activity. The increased aldosterone further increases the fluid retention. Thus there is a marked increase in plasma and extracellular volume which can manifest itself as ventricular dilation and central and peripheral edema. The long-term effects of all these factors on the heart can be disastrous. The heart is faced on the one hand with an increased workload with increased heart rate and stroke volume, and on the other hand, the oxygen carrying capacity of the blood is reduced by the anemia itself. The heart undergoes ‘remodeling’ with ventricular dilation and left ventricular hypertrophy (LVH). Both the SNS and RAAS contribute to this remodeling. Eventually the LV dilation and hypertrophy lead to myocardial cell death (apoptosis and necrosis), cardiac fibrosis, myocardiopathy and further CHF [14,15]. The CHF, by way of increased secretion of cytokines such as TNF alpha, can also cause anemia which completes the vicious circle.

	5. Increased susceptibility of the damaged heart to anemia

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
In patients with coronary artery disease the effects of anemia on the heart may be even more severe than in normal people. In the damaged heart, ischemia can occur at a higher Hb level than in those with a normal heart [16–19]. While patients with normal hearts undergoing surgery can tolerate low hemoglobin levels without increasing cardiovascular (CV) risk, those with coronary heart disease are more likely to have CV complications at these low Hb levels [16–19]. Elderly patients who have had a myocardial infarction and who have a hematocrit (Hct) of less than 30% are less likely to die if they are transfused [19]. Animal studies have confirmed these clinical findings [16,17]. They have demonstrated that reducing the diameter of coronary arteries in healthy animals can cause CHF, that CHF occurs at a higher Hb level in animals with coronary stenosis than it does in those animals with normal coronaries and that in the animals with stenosed coronary arteries who developed CHF when anemia was produced, the CHF disappeared when the anemia was corrected.

	6. Is anemia important in CHF?

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
All the above argue for a role of anemia in the production or worsening of CHF. But how relevant is this clinically in CHF? Judging from the medical literature anemia in CHF is not considered an important contributor to this condition. In the recent US guidelines on diagnosis and treatment of CHF, anemia is not even mentioned [20]. In studies looking at exacerbating causes of CHF, anemia is not considered to be a common or important contributor [21]. But is this really the case?

It could be argued that anemia is a positive factor because it is associated with reduced viscosity of the blood and therefore might allow the blood to flow more easily through the heart. However, a recent study analyzed the effect of anemia in CHF on mortality in the SOLVD study, a prospective controlled study of treatment of CHF patients with ACE inhibitors [22]. The mortality rate was found to increase with increasing severity of anemia and the anemia was found to be an independent risk factor for this increased CHF mortality. These results of increasing mortality related to anemia in CHF have recently been confirmed by another large CHF study [23] which also found that the anemia was associated with worse symptoms and decreased functional capacity.

	7. Lessons learned from the use of erythropoietin in the correction of anemia for the prevention and treatment of CHF in CRF patients before and while on dialysis

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
The last l5 years have seen a revolution in the treatment of anemia with the advent of EPO. This agent, produced in the kidney, stimulates bone marrow production of red blood cells (RBCs). Originally it was used primarily in hemodialysis and CRF predialysis patients where it was shown to have great benefits [5,24–26]. The improvement of the anemia in these patients has been associated with a reduction in ventricular dilation and a reduction in left ventricular mass and hypertrophy. Anemia was also found to be an independent risk factor for LVH, de novo and recurrent CHF, and cardiac mortality in dialysis patients. In addition many studies in dialysis patients have shown that the greater the level of Hb, the lower the risk of hospitalization and death. But the benefits of correction of anemia do not stop there. With the improvement in the Hb with EPO treatment quality of life improved dramatically, with improved cognitive function, an improvement in exercise capacity, depression, social relationships, sexual function, sleep, appetite and nutritional status [5,24,25]. Is it possible that what is called cardiac cachexia is, in many instances, nothing more than untreated anemia?

In addition, correction of anemia with erythropoietin is associated with several other benefits [5,24,25] including an increase in aerobic metabolism and less anaerobic metabolism and lactate production, improved peak oxygen utilization, improved skeletal muscle function, an improvement in angina pectoris, improved cerebral blood flow, improved amino acid metabolism, improved glucose metabolism, improved endothelial cell function and improved blood rheology. The high levels of 2,3, DPG in the young RBCs produced by EPO, improves the uptake of oxygen from the lungs and its release into the tissues. The RBC has many systems for handling oxidation radicals, so that the effects of these damaging substances are reduced with correction of the anemia. EPO treatment increases the antoxidant powers of the blood. This reduces lipid peroxidation, a key step in the production of atherosclerosis.

However, there is still some uncertainty about how much to increase the Hb level in hemodialysis patients. In a study of 1233 patients with clinical evidence of CHF or ischemic heart disease who were undergoing hemodialysis [27], half were assigned to receive enough EPO to maintain a Hct of 42% and the other half a Hct of 30%. The mortality rates decreased with increasing Hct values in both groups but there was no difference in the event-free survival in the two groups. The results in this selected group of patients, however, may not be applicable to non dialyzed CHF patients, and further studies are needed in this group to evaluate the optimum Hct level.

	8. Side effects of erythropoietin

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
EPO has a very low incidence of side effects and is easily administered subcutaneously once every 1–2 weeks in doses of 4000–10 000 International Units (IU). In these relatively low doses, hypertension is rarely caused or worsened. However, if the BP does become elevated it is almost always easily controlled with slight changes in antihypertensive medications.

All of this experience in renal failure patients suggests that EPO may be an ideal agent for the correction of anemia in CHF patients.

	9. Is correction of anemia useful in CHF patients?

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
We recently reported our experiences in the treatment of anemia in patients seen in our out patient CHF clinic, who were resistant to maximally-tolerated levels of CHF medications including ACE inhibitors, one of three beta-blockers carvedilol, bisoprolol or metoprolol, aldospirone, nitrates, digoxin, oral furosemide and intravenous (IV) furosemide [2,28]

We conducted a prospective trial wherein we administered subcutaneous erythropoietin (EPO) and IV iron (Venofer-iron sucrose) to 26 patients who had severe CHF and anemia (Hb<12 g%) and were resistant to the maximally tolerated therapy for CHF [2]. Mean duration of the treatment was 7.2±5.5 months. We found that Hb levels increased from 10.16±0.95 to 12.10±1.21 g%, and this increase was associated with an improvement in cardiac function [an increase in the mean left ventricular ejection fraction (LVEF) from 27.7±4.8 to 35.4±7.6%] and a decrease in the mean New York Heart Association (NYHA) functional class from 3.66±0.47 to 2.66±0.70). Furthermore, prior to the intervention, the GFR had been deteriorating at a mean rate of 0.95±1.31 ml min^–1. During treatment, the mean GFR increased by 0.85±2.77 ml min^–1 month^–1. In addition, the number of hospitalizations fell from a mean of 2.72±1.21 in the months before the trial to 0.22±0.65 for the same period of time after the anemia was corrected, an improvement of 91.9%. Particularly striking was the fact that this improvement took place despite a marked reduction in the dose of oral and intravenous furosemide. The doses of other CHF agents were kept constant [2].

In a subsequent controlled study [28] we treated anemia in the same manner as above in 16 severe resistant CHF patients (Group A) but not in 16 patients of a control group (Group B) over a mean of 8.2±2.6 months. In Group A we raised the Hb from a mean of 10.3±1.2 to 12.9±1.1 g%. Four patients in Group B died of CHF-related illnesses while none died in Group A. 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 to the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B. The results of these two studies suggest that the treatment of even mild anemia can have a profound effect on cardiac and renal status in CHF patients.

Of a total of 126 patients referred to our nephrology department with resistant CHF and anemia [29], 114 (90.5%) had a serum creatinine of at least 1.5 mg% and 69.8% were men. The mean age of the men was 73.0±10.9 and for the women 74.3±9.1. A history of diabetes, hypertension and hypercholesterolemia was found in 47.6%, 53.2% and 50% of patients, respectively. A LVEF of less than 45 was found in 81%. The main causes of CHF were considered to be ischemic heart disease in 78.6%, hypertension alone in 10.3%, valvular heart disease in 7.1% and idiopathic myocardiopathy in 4.0%. Patients were all treated in the same manner as in the previous two studies described above. The mean duration of treatment was 12.4±8.2 months (range 5–27 months). The effect of treatment on blood and clinical parameters is seen in Table 1. There was a significant increase in the Hb, Hct, serum ferritin, % Fe saturation and serum Fe. The mean serum creatinine did not change but the calculated GFR, which was falling before correction of the anemia, stabilized with the anemia treatment

View this table: [in this window] [in a new window]   Table 1 Values before and after treatment in the 126 congestive heart failure patients

 
There was a significant improvement in the NYHA functional class and in the LVEF. The fatigue/SOB visual analogue scale, which is a self assessment scale of the degree of fatigue and shortness of breath-SOB (with 0 being normal and 10 being extremely severe) showed that the treatment of anemia was associated with a marked and significant improvement in the patients’ assessment of their own level of fatigue/SOB. On a scale of 10 (10 being very severe fatigue and/or SOB), the patients noted a fall in the mean score from 8.9±1.4 to 2.7±1.9 over the treatment period.

There was a marked and significant fall in the number of hospitalizations after correcting the anemia. The mean systolic and diastolic blood pressures were similar before and after treatment.

Six patients (4.8%) eventually required dialysis and nine others (7.1%) died. The causes of death are seen in Table 2. None of the patients died from progressive CHF. Considering the age and condition of these patients the mortality rate is relatively low compared to what is usually seen in these patients [30].

View this table: [in this window] [in a new window]   Table 2 Causes of death in the nine CHF cases who died [29]

 
A recent double blind study of the use of EPO in severe CHF has confirmed some of our findings [31]. Over a 3-month period 86% of EPO-treated patients had an improvement in exercise capacity compared to none in the placebo group.

	10. Use of IV iron as a supplement to EPO for anemia in CHF

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
We have used IV iron in addition to EPO in the treatment of the anemia. This regimen is based on studies indicating that the effect of EPO is markedly reduced if IV iron is not added [32]. EPO stimulates the rapid production of erythrocytes in the marrow. If the iron supply is inadequate, the RBCs produced are extruded from the marrow with low levels of hemoglobin. Intravenous iron prevents or overcomes this functional iron deficiency. The oral route of iron administration usually does not supply enough iron to the EPO-stimulated bone marrow to produce the increased amount of Hb needed for the increased number of red blood cells produced. The new IV iron preparations such as iron sucrose and iron gluconate are very safe and have been approved for use all over the world. In contrast iron dextran, which was for years the main IV preparation used, not infrequently causes serious adverse side effects.

	11. The interactions of CHF and CRF

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Our studies also indicate that the correction of the anemia and the subsequent improvement in CHF are often associated with a slowing or stopping of the progression of the CRF. There is a dose–response relationship between the severity of CHF and the frequency and severity of CRF. In the study of the 142 patients attending our special outpatient CHF unit mentioned previously [2] the mean serum creatinine level was within normal range (1.18±0.38 mg%) in those with the mildest form of CHF (NYHA class 1), but increased steadily as CHF class rose, reaching 2.00±1.89 mg% in the patients with the most severe disease (NYHA 4). The percentage of patients with serum creatinine 1.5 mg% increased from 18.2% in the NYHA class 1 group to 58.2% in the NYHA class 4 group. The slowing of deterioration in renal function that we observed in our intervention studies [2,28,29] may be due to the improved cardiac function causing increased RBF and GFR. The stabilization of renal function is important for two reasons. An elevated serum creatinine is a major independent risk factor for death [22,23,33] in CHF. In addition, in some patients with CHF, renal function may progressively deteriorate to the point that the patient may require dialysis. In the 126 anemic CHF patients that we have treated [29], 6 (4.8%), as mentioned previously, eventually needed dialysis. All these patients had markedly elevated serum creatinine levels and severe CHF when first seen and it is possible that if they had been seen earlier and aggressively treated, the progression to dialysis could have been avoided or slowed.

	12. The cardio renal anemia syndrome

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
It would seem that a vicious circle is created in CHF, wherein CHF can cause CRF and both can then cause anemia due to either a reduction in EPO production, EPO utilization or both. The anemia further worsens the CHF which in turn further worsens the CRF which causes more disturbances with EPO, more anemia and so on. We have termed this lethal interaction of CHF, CRF and anemia the cardio-renal anemia (CRA) syndrome (Fig. 1). The good news is that the cycle can be disrupted at multiple sites by the combined approach of using CHF medications in the recommended doses and by correcting the anemia with subcutaneous EPO and IV iron administration.

View larger version (11K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 The cardio-renal anemia syndrome.

 

	13. Importance of multidisciplinary collaboration in the detection and treatment of CRA syndrome

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Over the last 2 years nephrologists at our center have been working in close cooperation with cardiologists, internists and family physicians in the hospital and in the community to correct the anemia associated with CHF. The increase in the awareness of these clinicians of the role of anemia in CHF has resulted in an eightfold increase in early referrals of patients with a combination of mild to severe CHF, mild CRF, and mild to moderate anemia—that is, the CRA syndrome, for treatment of their anemia. In this manner, these patients are being seen early, when therapy can still control all aspects of CHF and CRF and can slow or stop their progression.

As part of this multidisciplinary cooperation, our nephrologists are particularly involved in the control of the anemia, hypertension, nutritional status and secondary hyperparathyroidism of these CHF–CRF patients. The cardiologists for their part use an aggressive approach to the CHF, prescribing maximally tolerated doses of CHF medication and treating the many other complications encountered. As a result of this combined effort we have observed a marked improvement in outcome in these patients described above. We trust that the knowledge, interest and cooperation of nephrologists, cardiologist, internists and family physicians in the early detection and treatment of the CRA syndrome will open a new phase in the control of both cardiac and renal insufficiency and help avoid or slow the progression of both of these diseases.

	14. Summary

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 
Anemia is frequently seen in CHF and, without its correction, a large number of these patients will not benefit from standard CHF therapy. The administration of subcutaneous erythropoietin with IV iron supplementation is very efficient in the correction of this anemia and is associated with a remarkable improvement in clinical status. Clearly more controlled studies, and ones that are randomized and double blinded, should be carried out to confirm the findings summarized above.

	References

Top Abstract 1. Anemia and congestive... 2. Why should CHF... 3. How common is... 4. How can anemia... 5. Increased susceptibility of... 6. Is anemia important... 7. Lessons learned from... 8. Side effects of... 9. Is correction of... 10. Use of IV... 11. The interactions of... 12. The cardio renal... 13. Importance of... 14. Summary References

 

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