The European Journal of Heart Failure 5 (2003) 3–4
Editorial
Anaemia in heart failure: its diagnosis and management
Chronic heart failure (CHF) is a common syndrome w1x
affecting more than 20 million people world-wide and
approximately 7 million people in the European com-
munity. The incidence and prevalence of CHF have been
shown to increase sharply with age w2x. Prognosis is
poor; 12 week mortality was 14% in the recently report-
ed Euroheart survey w3x.
Anaemia as a cofactor in CHF has not been well eval-
uated and its contribution is ill defined w4,5x.
The following factors have to be considered:
1. There may be reduced intestinal iron uptake associ-
ated with cardiac cachexia and malabsorption.
2. Tumour necrosis factor alpha, which is increased in
patients with CHF, can lead to depression of bone
marrow and interferes with the action and utilisation
of erythropoietin and iron.
3. CHF activates the renin–angiotensin–aldosterone-
system and vasopressin, resulting in sodium and
water retention and dilutional anaemia.
4. CHF can lead to renal dysfunction due to renal vaso-
constriction and ischemia resulting in an increase in
erythropoietin. Usually renal anaemia develops in
chronic renal dysfunction with serum creatinine over
3.5 mgydl or a creatinine clearance below 30 mly
min.
5. Diabetes as well as arterial hypertension can con-
tribute to heart failure and are frequent concomitant
diseases. Both can also cause further renal
dysfunction.
6. High doses of ACE-inhibitors can impair the
response to erythropoietin treatment in hemodialysis
patients w6x.
7. Chronic anaemia contributes to CHF because an
increased cardiac output is required to deliver oxy-
gen to the tissues. This leads to an increase in myo-
cardial oxygen demands and stimulates volume
overload hypertrophy w7x.
8. Treatment of the disease underlying CHF, principally
coronary artery disease, with agents such as aspirin
and warfarin can contribute to blood loss and anae-
mia due to gastrointestinal bleeding.
1388-9842/03/$30.00 䊚 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
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9. A rightward shift of the oxyhemoglobin dissociation
curve on exercise has been shown in patients with
CHF w8x. Erythropoietin treatment can further
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increase 2,3 DPG levels with a further increase in
oxygen extraction w9,10x.
10. Renal failure, hypercirculation due to therapeutic
arterio-venous shunts and anaemia, hypertension as
well as left ventricular hypertrophy interact in vari-
ous ways and contribute further to heart failure and
vice versa to renal failure.
Taking into consideration all of the above mentioned
factors, anaemia favours the progression of heart failure.
Anaemia has been recognised to exacerbate pre-exist-
ing heart failure w11x. Furthermore recent literature sug-
gests a far more important role of anaemia in the natural
course of CHF. In addition, a vicious cycle between
anaemia, chronic renal failure and exacerbation of heart
failure can be assumed.
Thus it seems logical, that Silverberg et al. w12,13x
suggested treatment with a combination of erythropoietin
and intravenous iron. This combination has been shown
to be safe and effective in patients with CHF before
starting dialysis as well as in patients on dialysis. Intra-
venous iron administration seems to be more effective
than oral administration, possibly because of iron
absorption disturbances in CHF patients. Intravenous
iron therapy can reduce the need for high erythropoietin
doses, which it might be preferable to avoid since this
can lead to an increase in arterial pressure, which may
not be desirable. Improvement of symptoms of CHF and
exercise capacity has also been observed w12–14x.
These benefits might be more pronounced in the early
stages of CHF, than in patients with end stage CHF
under dialysis and recombinant erythropoietin therapy
w15x.
If treatment with erythropoietin and iron is preceded
by exclusion of other causes of anaemia, for example
intestinal blood loss or fluid overload, it might be quite
effective for improvement of symptoms and reduction of
4 Editorial
left ventricular size w5x. Prognostic benefits are unprov-
en, but cannot be excluded.
Recent studies have investigated a novel erythropoi-
esis stimulating protein (NESP) which has a three-times
longer half-life due to addition of two extra carbohydrate
chains w16x. NESP is a hyperglycosylated analogue of
recombinant human erythropoietin that was used in 1500
patients for stimulation of erythropoiesis.
In conclusion, moderate and severe anaemia of any
origin can exacerbate CHF. Patients with heart failure
may benefit from therapy of anaemia. Favourable influ-
ences on the long-term course are possible but so far
unproven. Further studies are needed.
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Anne Parsi
Franz Xaver Kleber
Department of Internal Medicine, UKB, Warener Street 7,
D-12683 Berlin, Germany
E-mail: fxkleber@ukb.de