Cardiology department of First affiliated Hospital to Xi’an Jiaotong University P.R Shaanxi

Authors:

MD EpiphanieVerlineTonleu Cardiology resident ;

Liu XiaohuaPhd Physiology and Pathophysiology department of Xi’an Jiaotong University

Recurrent anemia in a congestive heart failure patient and sudden death

Abstract

Sudden cardiac death is a public health issue affecting more than 23 million of people worldwide[1]While anemia affects about 1.62 billion people (95% CI: 1.50–1.74 billion) [2] In Heart failure patients, anemia is a consequence of the illness and represents a high risk to patient survival due to the lack of sufficient blood perfusion in these patients suffering from the inability to pump blood for the rest of the body. Throughout this observed case we expose an anemia case management for congestive heart disease patient.

A 68 years old woman comes in the hospital with a chief complaint of anemia relapse one month and half after the same complaint. She has been suffering from congestive left heart failure for the past 5 years which has progressed to type 3 heart failure and type 4 chronic renal failure these past months.

History of the disease

6 years ago, our patient suffered from endometrial cancer which was discovered in a local hospital after reporting postmenopausal bleeding. Transvaginal ultrasonography followed by endometrial biopsy examination revealed that the disease was only in stage type I a but the doctors requested total hysterectomy and lymph nodes resection to avoid the disease progression. She was later infused with combined Taxol andCarboplatin injections during 3 weeks,2 hoursand 30 minutes each times combined to radiotherapy. However although she was out of danger , one year later she suffered of a sudden heart arrest during an hospital stay for pulmonary infection and was quickly diagnosed of left heart failure. She was recommended FurosemideFroop® 1 pill of 40mg per day and Captopril ® 6,25 mg day and night 25 mg two or three times per day, with regular checkups.

One month ago, the patient came in the hospital due to extreme fatigue and was diagnosed of pernicious anemiathe first time due to a CBC of 6g/dL Hemoglobin .To improve her health she was perfused with A positive blood .while her state was slowly improved Heart echography suggested that the left heart failure was now a biventricular failure also called type 3 heart failure. Decreasedcardiac activity and damagewas also observed following the positively increase of Troponin test. The patient also was no longer able to pass urine with a decreased GFR < 60 ml/min/1.73 m2.Dialysis was suggested due to alleged type 4 chronic kidney diseases but the patient was sent home after 2 packs of blood transfusion,polysaccharideiron Niferex and recommendation and iron enriched diet before starting the dialysis therapy.

Digitalis was also administrated during the night and the patient was advice to follow up with the therapy until then. 1 pill every two days due to renal excretion of digitalis

[3]But blood transfusion may be associated with other adverse effects including immunosuppression with increased risk of infection, sensitization to HLA antigens, and iron overload.

3 weeks later our patient was admitted again for recurrent anemia and a hemoglobin level of 5 g/dL this time.

Another pack of blood was supplied again but 24 hours before further treatment could be supplied,the heart could apparently not propel the blood to the rest of the body and the patient was still complaining of weakness more than 2 hours after the therapy had started and had clammy extremities later on passed out.

Differential diagnosis

Aplastic anemia could not be considered but could be feared after a cancer therapy due to combined cytotoxic cells destruction and bone marrow destruction following chemotherapy and radiotherapy. However the patient was out of the cancer threat but congestive heart failure and leukemia was not found during this treatment.

Pernicious anemia was our diagnosis and theassociated treatment was iron and vitamin B12 supply however, the treatment did not bring the expectation we had. Cancer metastasis

No relapse of cancer was observed after abdominal X-ray

Type 3 heart failure and type 4 chronic renal failure was diagnosed.

We could not help the patient before the ultimate heart arrest.

Discussion

It resorts from this case that anemia diagnosis in immune depressed patients should be followed to extensive investigations to avoid worsening the patient case. Transfusion and oral iron supplements do not significantly replenish the iron stores in the body and further studies that analyzed hemoglobin as a continuous variable, showed that a 1-g/dL decrease in hemoglobin was associated with significant increased mortality risk. Although erythropoietin levels are modestly elevated in patients with CHF, the increase is less than that observed in other anemic populations. Accordingly, anemia in CHF may be responsive to exogenous erythropoietin supplementation. [4]The primary mechanism by which erythropoietin stimulates red blood cell production is inhibition of apoptosis of bone marrow erythrocyte progenitors.

There are 3 currently available erythropoietic agents for treatment of anemia: epoetin-α, epoetin-β (both of which are recombinant human erythropoietin [rHuEpo]), and darbepoetin-α.31 . RHuEpo was first synthesized in 1985, 2 years after the erythropoietin gene was cloned, and was approved by the US Food and Drug Administration for clinical use for treatment of anemia in end-stage chronic kidney disease in 1988. Early studies in dialysis-dependent patients with chronic kidney disease showed that intravenous or subcutaneous administration of 150 to 200 IU/kg per week (in 1 to 3 divided doses) increased hemoglobin concentrations to 10 to 12 g/dL in 83% to 90% of anemic patients with chronic kidney disease. Approximately 25% of the administered dose is absorbed after subcutaneous dosing, but the plasma half-life is increased to >24 hours. The amount of subcutaneous rHuEpo needed to achieve hemoglobin targets in patients with chronic kidney disease is approximately 25% less than that needed for intravenous dosing. [5] Darbepoetin-α is a long-acting, N-linked supersialylated analog of human erythropoietin approved by the US Food and Drug Administration for the treatment of anemia in patients with chronic kidney disease in 2001.

Compared with both native and recombinant erythropoietin, it has stronger affinity for erythropoietin receptor and longer plasma half-life of approximately 48 hours, with consequent longer dosing intervals of 1 to 2 weeks during maintenance therapy. Although intravenous iron sucrose and iron gluconate preparations are not associated with anaphylaxis and are generally well tolerated in chronic kidney disease populations, there are concerns that excess iron stores may be associated with increased risk of infection and cardiovascular events.

Additional work is needed to determine the safety and efficacy of intravenous iron supplementation in anemic patients with CHF with functional iron deficiency.

On the basis of available data, we recommend serial measurement of hemoglobin in patients with CHF at 6-month intervals in order to identify the subset of patients with anemia who may benefit from further assessment and treatment. In patients with anemia (defined by World Health Organization criteria), further assessment including evaluation for iron or other nutritional deficiencies and estimation of glomerular filtration rate should be performed. [6]For the subpopulation of patients with CHF with moderate-to-severe anemia (hemoglobin <11 g/dL) and concomitant moderate to severe chronic kidney disease (estimated glomerular filtration rate ≤60 mL/min),[7] current guidelines of the National Kidney Foundation recommend treatment with erythropoietic agents and supplemental iron to a target hemoglobin of 12 g/dL.

Conclusion

Although in developing countries these treatments are not available they should be sought and the guidelines of the WHO for anemia management in chronic heart failure be respected.

Preliminary studies suggest potential beneficial effects of treatment of anemia with erythropoietic agents on exercise capacity and quality of life.

References

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[2]. de Benoist B et al.,eds.Worldwide prevalence of anaemia 1993-2005.WHO Global Database on Anaemia Geneva, World Health Organization, 2008

[3]. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation.

[4]. Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R, Schwartz D, Yachnin T, Steinbruch S, Shapira I, Laniado S, Iaina A. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am CollCardiol. 2001; 37: 1775–1780.

[5]. Cleland JG, Sullivan JT, Ball S, Horowitz JD, Agoram B, Rosser D,

Yates W, Tin L, Fuentealba P, Burton PB. Once-monthly administration of darbepoetinalfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation. J CardiovascPharmacol.2005; 46: 155–161.

[6]. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005

[7]. Contemporary Reviews in Cardiovascular Medicine Anemia in Chronic Heart Failure

Prevalence, Etiology, Clinical Correlates, and Treatment Options

Yi-Da Tang, MD, PhD;

Stuart D. Katz, MD