To access this material please log in or register

Register Authorize

Regression of structural and functional rearrangements in heart and kidneys of patients with chronic heart failure in combination with permanent atrial fibrillation during the treatment with omega-3 polyunsaturated fatty acids.

Nikonova Yu. N., Koziolova N. A., Shilova Ya. E., Agafonov A. V., Polyanskaya E. A.

Keywords: omega-3 fatty acids, atrial fibrillation, CHF

DOI: 10.18087/rhfj.2013.4.1832

Background. Cardio- and nephroprotective effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in the treatment of CHF patients, who have had ACS and presently have atrial fibrillation (AF), are a subject of intensive studying and implementing in clinical practice. Aim. Evaluating the time course of CHF and the regression of structural and functional remodeling of heart and kidneys in patients with CHF of ischemic etiology associated with permanent AF receiving ω-3 PUFAs. Materials and methods. 60 patients with CHF of ischemic etiology associated with permanent AF were examined and randomized to two equal groups for identification of ω-3 PUFA cardio- and nephroprotection as compared with the standard therapy for CHF. The treatment duration was 6 months. Structure and function of the heart and kidneys were evaluated using standard echoCG with tissue visualization of diastolic movement rates of mitral valve annulus and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), glomerular filtration rate, creatinine clearance, cystatin C, and tissue inhibitor of matrix proteinases-1 (ТIMP-1) were performed. Results. Addition of ω-3 PUFAs to the standard therapy of patients with CHF of ischemic etiology associated with permanent AF improves the clinical course of disease, enhances the exercise tolerance as shown by results of 6min walk test (p<0.001), reduces atrial and ventricular myocardial stress as evaluated by changes in NT-proBNP (p=0.036), alleviates diastolic dysfunction (p<0.001) and LV myocardial hypertrophy (p=0.034), increases LV EF (p<0.001), provides regression of kidney function disorders as shown by the evaluation of cystatin C changes (p=0.002), and restores favorable collagenolysis in myocardial and renal intracellular matrix as shown by TIMP-1 changes (p<0.001). Conclusion. Omega-3 PUFAs added to the therapy of patients with CHF and permanent AF display pronounced cardio- and nephroprotective properties by improving the clinical condition of patients and by favorable structure and function remodeling of the left-side heart and kidneys due to prevention of fibrosis and alleviation of myocardial stress.
  1. Lardizabal JA, Deedwania PC. Atrial fibrillation in heart failure. Med Clin North Am. 2012;96 (5):987–1000.
  2. Capucci A, Matassini MV. Atrial fibrillation and heart failure. Recenti Prog Med. 2010;101 (4):163–169.
  3. Piot O. Atrial fibrillation and heart failure: a dangerous criminal conspiracy. Ann Cardiol Angeiol (Paris). 2009;58 (Suppl 1):S14–16.
  4. Larned JM, Raja Laskar S. Atrial fibrillation and heart failure. Congest Heart Fail. 2009;15 (1):24–30.
  5. Wang TJ, Larson MG, Levy D et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003;107 (23):2920–2925.
  6. Rewiuk K, Wizner B, Fedyk-Lukasik M et al. Epidemiology and management of coexisting heart failure and atrial fibrillation in an outpatient setting. Arch Gerontol Geriatr. 2012;55 (1):91–95.
  7. Беленков Ю. Н., Мареев В. Ю., Агеев Ф. Т. и др. Современный образ пациента с ХСН в Европейской части Российской Феде­рации (госпитальный этап). Журнал Сердечная недостаточность. 2011;12 (5):255–259.
  8. Avitall B, Bi J, Mykytsey A, Chicos A. Atrial and ventricular fibrosis induced by atrial fibrillation: evidence to support early rhythm control. Heart Rhythm. 2008;5 (6):839–845.
  9. Stanojević D, Apostolović S, Janković-Tomasević R et al. Prevalence of renal dysfunction and its influence on functional capacity in elderly patients with stable chronic heart failure. Vojnosanit Pregl. 2012;69 (10):840–845.
  10. Witman MA, Fjeldstad AS, McDaniel J et al. Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond. Hypertension. 2012;60 (3):659–668.
  11. Ananthapanyasut W, Napan S, Rudolph EH et al. Prevalence of atrial fibrillation and its predictors in nondialysis patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010;5 (2):173–181.
  12. Boldt LH, Schwenke C, Parwani AS et al. Determinants of morta­lity in patients with heart failure and atrial fibrillation during long-term follow-up. Acta Cardiol. 2011;66 (6):751–757.
  13. O'Meara E, Khairy P, Blanchet MC et al. Mineralocorticoid receptor antagonists and cardiovascular mortality in patients with atrial fibrillation and left ventricular dysfunction: insights from the Atrial Fibrillation and Congestive Heart Failure Trial.Circ Heart Fail. 2012;5 (5):586–593.
  14. Lechat P, Hulot JS, Escolano S et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001;103 (10):1428–1433.
  15. Van Veldhuisen DJ, Aass H, El Allaf D et al. Presence and development of atrial fibrillation in chronic heart failure. Experiences from the MERIT-HF Study. Eur J Heart Fail. 2006;8 (5):539–546.
  16. Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream thera­pies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention.Europace. 2011;13 (3):308–328.
  17. Stone NJ. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI) – Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors. Curr Cardiol Rep. 2000;2 (5):445–451.
  18. Marchioli R, Levantesi G, Silletta MG et al. Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial. Expert Rev Cardiovasc Ther. 2009;7 (7):735–748.
  19. Maaløe T, Schmidt EB, Svensson M et al. The effect of n-3 polyunsaturated fatty acids on leukotriene B4 and leukotriene B5 production from stimulated neutrophil granulocytes in patients with chronic kidney disease. Prostaglandins Leukot Essent Fatty Acids. 2011;85 (1):37–41.
  20. McMurray JJ, Adamopoulos S, Anker SD et al. Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14 (8):803–869.
  21. Гутор С. С. Молекулярные маркеры послеоперационного ремоделирования сердца у больных ишемической кардиомиопатией. Сборник статей по материалам Международной 69‑й научной итоговой студенческой конференции, посвященной 200‑летию со дня рождения Н. И. Пирогова под редакцией академика РАМН В. В. Новицкого, член. корр. РАМН Л. М. Огородовой. – Томск. 2010. – 293–295.
  22. Короленко Т. А., Черканова М. C., Филатова Т. Г., Бравве И. Ю. Возрастные изменения содержания цистатина С и С-реактивного белка у здоровых лиц. Terra Medica nova. 2007;1:21–22.
  23. Alboni P, Gianfranchi L, Pacchioni F. Upstream therapy of atrial fibrillation in patients with heart failure. G Ital Cardiol (Rome). 2009;10 (9):566–571.
  24. Pfeffer MA, Swedberg K, Granger CB et al. CHARM Investigators and Committees. Effects of candesartan on mortality and morbi­dity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362 (9386):759–766.
  25. Konstam MA, Neaton J D, Dickstein K et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374 (9704):1840–1848.
  26. Cleland JG, Tendera M, Adamus J et al. PEP – CHF Investigators The perindopril in elderly people with chronic heart failure (PEP–CHF) study. Eur Heart J. 2006;27 (19):2338–2345.
  27. Dickinson MG, Ip JH, Olshansky B et al. SCD-HeFT Investigators. Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implan­table defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Am Heart J. 2007;153 (4):573–578.
  28. Macchia A, Grancelli H, Varini S, et al. Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) Trial. J Am Coll Cardiol. 2013 Jan 29;61 (4):463–468.
  29. Mozaffarian D, Marchioli R, Macchia A et al. Fish oil and postope­rative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA. 2012;308 (19):2001–2011.
  30. Rix TA, Christensen JH, Schmidt EB. Omega-3 fatty acids and cardiac arrhythmias. Lancet. 2010;376 (9740):540–550.
  31. de Lorgeril M, Salen P. New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids. BMC Med. 2012;10:50.
  32. Khawaja O, Gaziano JM, Djoussé L. A meta-analysis of omega-3 fatty acids and incidence of atrial fibrillation. J Am Coll Nutr. 2012;31 (1):4–13.
  33. Kwak SM, Myung SK, Lee YJ et al. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analy­sis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172 (9):686–694.
  34. Hu FB, Manson JE. Omega-3 fatty acids and secondary prevention of cardiovascular disease-is it just a fish tale?: comment on «Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease». Arch Intern Med. 2012;172 (9):694–696.
  35. Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr. 2012;142 (3):614S-625S.
  36. Sakabe M, Shiroshita-Takeshita A, Maguy A et al. Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling. Circulation. 2007;116 (19):2101–2109.
  37. Lau DH, Psaltis PJ, Carbone A et al. Atrial protective effects of n-3 polyunsaturated fatty acids: a long-term study in ovine chronic heart failure. Heart Rhythm. 2011;8 (4):575–582.
  38. Krum H, Jelinek NV, Stewart S et al. 2011 Update to National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines for the prevention, detection and management of chronic heart failure in Australia, 2006. Med J Aust. 2011;194 (8):405–409.
  39. Беленков Ю. Н., Мареев В. Ю., Арутюнов Г. П. и др. Согла­сованное мнение экспертов о роли этиловых эфиров омега-3 полиненасыщенных жирных кислот 90 % для лечения и профилактики хронической сердечной недостаточности (заключение совещания экспертов, июнь 2011 г.). Кардиология. 2011;51 (9):89–91.
  40. Billman GE. Effect of dietary omega-3 polyunsaturated Fatty acids on heart rate and heart rate variability in animals susceptible or resistant to ventricular fibrillation. Front Physiol. 2012;3:71.
  41. Zhao YT, Shao L, Teng LL et al. Effects of n-3 polyunsaturated fatty acid therapy on plasma inflammatory markers and N-terminal pro-brain natriuretic peptide in elderly patients with chronic heart failure..J Int Med Res. 2009;37 (6):1831–1841.
  42. McLennan PL, Abeywardena MY, Dallimore JA, Raederstorff D. Dietary fish oil preserves cardiac function in the hypertrophied rat heart. Br J Nutr. 2012;108 (4):645–654.
  43. Duda MK, O'Shea KM, Stanley WC. omega-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mecha­nisms and clinical potential. Cardiovasc Res. 2009;84 (1):33–41.
  44. Fang Y, Favre J, Vercauteren M,Fundam et al. Reduced cardiac remodelling and prevention of glutathione deficiency after omega-3 supplementation in chronic heart failure. Clin Pharmacol. 2011;25 (3):323–332.
  45. Laurent G, Moe G, Hu X et al. Long chain n-3 polyunsaturated fatty acids reduce atrial vulnerability in a novel canine pacing model. Cardiovasc Res. 2008;77 (1):89–97.
  46. Chen J, Shearer GC, Chen Q et al. Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP / protein kinase G signaling in cardiac fibroblasts. Circulation. 2011;123 (6):584–593.
  47. Mozaffarian D. Fish, n-3 fatty acids, and cardiovascular haemodynamics. J Cardiovasc Med (Hagerstown). 2007;8 (Suppl 1):S23–26.
  48. Gopinath B, Harris DC, Flood VM et al. Consumption of long-chain n-3 PUFA, α-linolenic acid and fish is associated with the prevalence of chronic kidney disease. Br J Nutr. 2011;105 (9):1361–1368.
  49. Priante G, Musacchio E, Valvason C et al. Further insights about the beneficial effects of n-3 fatty acids in the early molecular events of renal fibrosis in vitro. J Nephrol. 2013;26 (4):652–659.
  50. Garman JH, Mulroney S, Manigrasso M et al. Omega-3 fatty acid rich diet prevents diabetic renal disease. Am J Physiol Renal Physiol. 2009;296 (2):F306–316.
  51. Takase O, Hishikawa K, Kamiura N et al. Eicosapentaenoic acid regulates IκBα and prevents tubulointerstitial injury in kidney. Eur J Pharmacol. 2011;669 (1-3):128–135.
  52. Cicero AF, Reggi A, Parini A, Borghi C. Application of polyunsaturated fatty acids in internal medicine: beyond the established cardiovascular effects. Arch Med Sci. 2012;8 (5):784–793.
Nikonova Yu.N., Koziolova N.A., Shilova Ya.E. et al. Regression of structural and functional rearrangements in heart and kidneys of patients with chronic heart failure in combination with permanent atrial fibrillation during the treatment with omega-3 polyunsaturated fatty acids. Russian Heart Failure Journal. 2013;14 (4):181-190

To access this material please log in or register

Register Authorize
Ru En