Abstract

The Research Objective: The purpose of this study is, given the impact of anemia on the clinic and the course of chronic heart failure (CHF), based on optimal diagnostic methods, the development of new differentiated methods for treating patients with CHF and anemia, including erythropoietin preparations methoxypolyethylene glycol epoetin beta (MPEB) and intravenous (IV) iron in combination with basic therapy.

The Research Methods: 127 patients with CHF of ishemic aethology were included in the study, surveyed. The mean age of patients was 60,6 ± 1,4 years. Of these, 93 patients were diagnosed with anemia. As a control group, 34 patients with CHF without anemia were examined. According to the therapeutic tactics with the use of combination MPEB at dose of 0,60 mсg/kg (50 units) and IV iron III hydroxide sucrose complex at a dose of 200 mg (Venofer), all patients, depending on therapeutic tactics, 2 groups. In all patients, the levels of Hb, ferrithin, of transferrin saturation (TS), erythropoietin (EPO), NTproBNP, IL-1,IL-6, TNF-α in blood plazma, parameters of systolic and diastolic function of left ventricular (LV) of methods doppler echocardiography before and after treatment..

The Research Analysis: The study showed that as a result of the negative effect of anemia on the CHF clinic, there is a decrease or absence of the effect of drugs of the baseline: positive dynamics of LVEF, LVMM, parameters of LV diastolic function and test with 6-MWT absent. There is no positive dynamics of Hb, Ht, ferritin, TS, EPO, NTproBNP, IL-1, IL-6 and TNF-α levels in blood plasma in patients with I-IV NYHA class CHF with anemia against baseline therapy.

The Research Results: The results of the parameters of the systolic function of the LV in patients with CHF I-II NYHA class with anemia of group II on the background of the therapy. There is an increase in LVEF by 12.2% (p < 0.001) on the background of combined MPEB therapy with IV [III] hydroxide sucrose complex. In patients in CHF with anemia and hypoerithropoietinemia with ID, use combined therapy with of the MPEB and IV iron Venofer. The levels of Hb increase 8,4% (p < 0,01), Ht, ferritin, TS, EPO, NTproBNP, IL-6 are positive. The indicator of 6-MWT was significantly increased by 21,6% (p < 0,001) and 64,9% (p < 0,001), respectively. There is an increase in LVEF by 12.2%. The 6-MWT significantly increased to 64,9 %

The Research Conclusion: The patients in CHF with anemia, combined therapy with the appointment of the MPEB and IV iron contributes to reliable positive dynamics of Hb, ferritin, TS and EPO, LV myocardium. In the treatment of patients in CHF with anemia, ia, there is a need for differentiation depending on the levels of such important parameters as plasma ferritin, TS and EPO.

Keywords: Heart Failure; Anemia; Erythropoietin; Ferritin; Methoxypolyethyleneglycolepoetin Beta; Iron (III) Sucrose

References

1. Mozaffarian D., et al. “Heart disease stroke statistics -2015 update: a report from the American Heart Association”. Circulation 131 (2015): e29-e322.
2. Van Deursen VM., et al. “Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey”. European Journal of Heart Failure1 (2014): 103-111.
3. O'Meara E., et al. “Clinical correlates and consequences of anaemia in broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Mobility (CHARM) Program”. Circulation7 (2006): 986-994.
4. Lindenfeld J. “Prevalence of anemia and effects on mortality in patients with heart failure”. American Heart Journal3 (2005): 391-401.
5. Valeur N., et al. “Anaemia is an independent predictor of mortality in patients with left ventricular systolic dysfunction following acute myocardial infarction”. European Journal of Heart Failure 8 (2006): 577-584.
6. Maggioni AP., et al. “Prevalence and prognostic role of anemia in patients with heart failure in the IN-CHA Registry and the Val-He FT trial”. European Heart Journal 23 (2002): 272.
7. Jhund PS., et al. “Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people”. Circulation 119 (2009): 515-523.
8. Larina VN., et al. “Anemic syndrome of patients in chronic heart failure”. Russian Cardiology Journal 3 (2010): 34-40.
9. Silverberg D., et al. “The interaction between heart failure, renal failure and anemia - the cardio-renal anemia syndrome”. Blood Purify 22 (2004): 277-284.
10. Kleijn L., et al. “Should erythropoietin treatment in chronic heart failure be haemoglobin targeted?”. European Journal of Heart Failure 12 (2010): 215-216.
11. Mancini DM., et al. “Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure”. Circulation 107 (2003): 294-299.
12. Palazuolli A., et al. “Erythropoietin improves anaemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization n in patients with chronic heart failure and anaemia”. American Heart Journal 152 (2006): 1096.e9-1096.e15.
13. Palazuolli A., et al. “Effect of beta erythropoietin treatment of left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anaemia syndrome”. American Heart Journal 154 (2007): 645.e9-645.e15.
14. Ponikowski P., et al. “Effect of darbepoetinalfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial”. Journal of the American College of Cardiology7 (2007): 753-762.
15. van Veldhuisen DJ., et al. “Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbopoietinalfa in patients with heart failure and anemia”. European Heart Journal 28 (2007): 2208-2216.
16. Parissis JT., et al. “Effect of Darbepoetin alpha on right and left ventricular systolic and diastolic function in anaemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy”. American Heart Journal 155 (2008): 751e751-e757.
17. Kourea K., et al. “Effects of darbepoetin-alpha on quality of life and emotional stress in anemic patients with chronic heart failure”. European Association for Cardiovascular Prevention and Rehabilitation 3 (2008): 365-369.
18. Parissis JT., et al. “Effects of Darbepoetin Alfa on plasma mediators of oxidative and nitrative stress in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy”. American Journal of Cardiology 103 (2009): 1134-1138.
19. Silverberg D., et al. “The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations”. Journal of the American College of Cardiology 35 (2000): 1737-1744.
20. Silverberg DS., et al. “The effect оf correction mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study”. Journal of the American College of Cardiology 37 (2001): 1775-1780.
21. Silverberg DS., et al. “The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization”. Clinical Nephrology 58 (2002): S37-S45.
22. Comin-Colet J., et al. “A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin for the in elderly patients with advanced chronic heart failure and cardiorenal anemia syndrome: influence on neurohormonal activation and clinical outcomes”. Journal of Cardiac Failure 15 (2009): 727-735.
23. Drakos SG., et al. “Anemia in chronic heart failure”. Congest Heart Failure2 (2009): 87-92.
24. Okonko DO., et al. “Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial”. Journal of the American College of Cardiology 2 (2008): 103-112.
25. Anker SD., et al. “Ferric carboxy-maltose in patients with heart failure and iron deficiency”. The New England Journal of Medicine25 (2009): 2436-2448.
26. Pagourelias E., et al. “Cardiorenal Anemia Syndrome: Do Erythropoietin and Iron Therapy Have a Place in the Treatment of Heart Failure?” Angiology 60 (2009): 74-81.
27. Klip IT., et al. “Iron deficiency in chronic heart failure: an international pooled analysis”. American Heart Journal4 (2013): 575-582.e3.
28. Natasha P Arora., et al. “Anemia and Iron Deficiency in Heart Failure”. Heart Failure Clinics2 (2014): 281-294.
29. Arora NP and Ghali JK. “Iron deficiency anemia in heart failure”. Heart Failure Review4 (2013): 485-501.
30. Caira C., et al. “Heart failure and iron deficiency anemia in Italy: results from CARMES-1 registry”. Future Cardiology3 (2013): 437-444.
31. Bergmann MW. “Chronic, low-dose epoietin treatment following PCI significantly improves left ventricular ejection fraction in ischemic heart failure”. Presented at: ESC Congress 2009; Barcelona, Spain (2009).
32. Parissis JT., et al. “Effect of Darbepoetin alpha on right and left ventricular systolic and diastolic function in anaemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy”. American Heart Journal 155 (2008): 751e751-e757.
33. Cosyns B., et al. “Effects of erythropoietin administration on mitral regurgitation and left ventricular remodeling in heart failure patients”. International Journal of Cardiology 138.3 (2010): 306-307.
34. Von Haehling S., et al. “Anemia in heart failure: an overview of current concepts”. Future Cardiology1 (2011): 119-129.
35. Jankowska EA., et al. “Iron status in patients with chronic heart failure”. European Heart Journal11 (2013): 827-834.
36. Attanasio PH., et al. “Role of Iron Deficiency and Anemia in Cardio-Renal Syndromes”. Seminars in Nephrology1 (2012): 57-62.
37. Kapoor M., et al. “Outcomes of patients with chronic heart failure and iron deficiency treated with intravenous iron: a meta-analysis”. Cardiovascular and Hematological Disorders-Drug Targets 1 (2013): 35-446.
38. RED-HF trial - reduction of Events with Darbopoietin Alfa in Heart Failure Trial (Clinical Trials.govidentifier: NCT00358215). An ongoing phase 3 study that will have major importance in determining and defining the use of erythropoietin therapy in anemic patients with heart failure (2008).
39. McMurray JJ., et al. “Design of the Reduction of Events with Darbepoetinalfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial”. European Journal of Heart Failure8 (2009): 795-801.
40. Swedberg K., et al. “Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure (TREAT)”. The New England Journal of Medicine 368 (2013): 1210-1219.
41. Pfeffer MA., et al. “A trial of darbepoetinalfa in Type 2 diabetes and chronic kidney disease”. The New England Journal of Medicine 361 (2009): 2019-2032.
42. Desai A., et al. “Impact of erythropoiesis-stimulating agents on morbidity and mortality in patients with heart failure: an updated, post-TREAT meta-analysis”. European Journal of Heart Failure 12 (2010): 936-942.
43. Streja E., et al. “Erythropoietin, iron depletion, and relative thrombocytosis: a possible explanation for hemoglobin-survival paradox in hemodialysis”. American Journal of Kidney Diseases 4 (2008): 727-736.
44. Szczech LA., et al. “Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes”. Kidney International6 (2008): 791-798.
45. Bohlius J., et al. “Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials”. The Lancet9674 (2009): 1532-1542.
46. Klapholz M., et al. “The safety and tolerability of darbepoetin alfa in patients with anaemia and symptomatic heart failure”. European Journal of Heart Failure 11 (2009): 1071-1077.
47. Macdouga llIC and Eckardt KU. “Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia”. Lancet 368 (2006): 947-953.
48. Domling A., et al. “Towards erythropoietin mimicking small molecules”. Bioorganic and Medicinal Chemistry Letters 17 (2007): 379-384.
49. Sulowicz W., et al. “On behalf of the PROTOS Study Investigators. Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dyalysis converted directly from epoetin one to three times weekly”. Clinical Journal of the American Society of Nephrology 2 (2007): 637-646.
50. Locatelli F., et al. “Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)”. Nephrology Dialysis Transplantation 19 (2004): 121-132.

Citation

Citation: Kamala Zahidova and Faik Guliyev. “New Opportunities in the Treatment of Anemic Syndrome in Chronic Heart Failure". Acta Scientific Cardiovascular System 1.6 (2022): 14-26.

Copyright

Copyright: © 2022 Kamala Zahidova and Faik Guliyev. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.