EFFECTS OF TRIMETAZIDINE ON THE TRANSMITRAL BLOOD FLOW IN PATIENTS WITH DIASTOLIC HEART FAILURE

Aim. To study effects of trimetazidine on the left ventricular diastolic dysfunction in patients with combination of ischemic heart disease (IHD) and arterial hypertension (HT). Material and methods. Patients with IHD and HT (n=154) were divided into two treatment groups. Patients of the main groups (n=72) received standard therapy and trimetazi- dine 35 mg twice a day. The patients of the control group (n=82) received only standard therapy. Echocardiographic parameters, including mitral Doppler flow indices were as- sessed at baseline and after 2 months.
Subgroups of patients were identified by type of left ventricle diastolic function according to echocardiographic data. Changes in echocardiographic indicators were evaluated in these subgroups separately and compared in the main and control groups.
Results. The subgroups of patients with impaired relaxation (n=54), pseudonormalization (n=48) and restriction (n=52) were identified in the main and control groups according to echocardiographic data. A significant increase in the period of early left ventricle filling (27.6%, p<0.05) and the ratio of the two phases of left ventricle filling (37.8%, p<0.001) were found in patients with impaired relaxation treated with trimetazidine. Other studied parameters of mitral flow in the other patient subgroups were not significantly changed. Conclusion. Trimetazidine 70 mg daily in the 2 month treatment of diastolic heart failure in patients with IHD and HT resulted in significant improvement of some indicators of mitral blood flow only in patients with type I diastolic dysfunction (impaired relaxation).

1. Amosova EN. Metabolic therapy myocardial damage caused by ischemia. A new approach to the treatment of coronary artery disease and heart failure. Ukrainian Journal of Cardiology 2000; (4): 86-92. Russian (Амосова Е.Н. Метаболическая терапия повреждений миокарда, обусловленных ишемией. Новый подход к лечению ишемической болезни сердца и сердечной недостаточности. Укра- инский Кардиологический Журнал 2000; (4): 8692).

2. Golikov A.P., Bojcov S.A., Mihin V.P. Free radical oxidation and cardiovascular disease: correction of antioxidants. Physician 2003; (4): 70-4. Russian (Голиков А.П., Бойцов С.А., Михин В.П. Свободнорадикальное окисление и сердечно-сосудистая патология: коррекция антиоксидантами. Лечащий Врач 2003; (4): 70-4).

3. Kalvinsh IJ. Mildronat and trimetazidin: similarities and differences in their action. Terra Medica Nova 2002, (3): 3-15. Russian (Калвиньш И.Я. Милдронат и триметазидин: сходство и различие в их действии. Terra Medica Nova 2002; (3): 3-15).

4. The EMIP-FR Group. Effect of 48-h trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial. Eur Heart J 2000; 21:1537-46.

5. Fedulaev JN, Korochkin IM, Fedoseyeva OS. The dynamics of the variance interval QT, heart rate variability, circadian index and duration of silent myocardial ischemia during therapy trimetazidom. Abstracts of the XIII Russian National Congress "Man and medicine." Moscow, April 5-8, 2006: 631. Russian (Федулаев Ю.Н., Корочкин И.М., Федосеева О.С. Динамика дисперсии интервала QT, вариабельности сердечного ритма, циркадного индекса и продолжительности безболевой ишемии миокарда на фоне терапии триметазидом. Тезисы докладов XIII Российского национального конгресса «Человек и лекарство». Москва, 5-8 апреля 2006: 631).

6. Shchukin YuV, Ryabov AE. Chronic ischemic heart disease in elderly and senile age. Manual for physicians. Samara: Volga-Business; 2008. Russian (Щукин Ю.В., Рябов А.Е. Хроническая ишемическая болезнь сердца в пожилом и старческом возрасте. Пособие для врачей. Самара: Волга-Бизнес; 2008).

7. Zharova EA, Lepakhin VK, Fitilev SB. Trimetazidine and others in the combination therapy of angina (TACT- Effect of Trimetazidine in patients with stable effort Angina in Combination with existing Therapy). Heart 2002, 1 (2): 6-11. Russian (Жарова Е.А., Лепахин В.К., Фитилев С.Б. и др. Триметазидин в комбинированной терапии стенокардии напряжения (TACT – Effect of Trimetazidine in patients with stable effort Angina in Combination with existing Therapy). Сердце 2002; 1 (2): 6-11).

8. Kosarev VV, Babanov SA Clinical pharmacology of drugs used in cardiovascular diseases. Samara: Ofort; 2010. Russian (Косарев В.В., Бабанов С.А. Клиническая фармакология лекарственных средств, применяемых при сердечно-сосудистых заболеваниях. Самара: Офорт; 2010).

9. Kantor P.F., Lucien A., Kozak R. et al. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. J Circ Res 2000; 86 (5): 580-8.

10. Vasyuk JA, Kulikov KG, Kudryakov ON, Krikunova OV. Mitochondrial dysfunction in the pathogenesis of acute myocardial infarction: the principles of diagnosis and treatment of myocardial cytopro- tector. Russian Medical News 2008; 13 (2): 36-41. Russian (Васюк Ю.А., Куликов К.Г., Кудряков О.Н., Крикунова О.В. Митохондриальная дисфункция в патогенезе острого инфаркта миокарда: принципы диагностики и терапии миокардиальными цитопротекторами. Российские Медицинские Вести 2008;13(2): 36-41).

11. Rysev AV Zagashvili IV, Sheipak BL, Litvinenko VA. Experience with the cytoprotective agents in acute coronary syndrome and myocardial infarction. Terra Medica Nova 2003; (1): 12-14. Russian (Рысев А.В., Загашвили И.В., Шейпак Б.Л., Литвиненко В.А. Опыт применения цитопротекторов при остром коронарном синдроме и инфаркте миокарда. Terra Medica Nova 2003; (1): 12-14).

12. Gordeev, IG, Luchinkina EE, Lyusov VA. Antioxidant effect cardioprotector Mildronate in patients un- dergoing coronary revascularization. Russian Journal of Cardiology 2009; (1): 31-7. Russian (Гордеев И.Г., Лучинкина Е.Е., Люсов В.А. Антиоксидантный эффект кардиопротектора Милдроната у пациентов, подвергшихся коронарной реваскуляризации. Российский Кардиологический Журнал 2009; (1): 31-7).

13. Sirkin AL, Doletsky AA. Trimetazidine in the treatment of coronary heart disease. Clinical Pharmacology and Therapy 2001; 10 (1): 1-4. Russian (Сыркин А.Л., Долецкий А.А. Триметазидин в лечении ишемической болезни сердца. Клиническая Фармакология и Терапия 2001; 10 (1): 1-4).

14. Shalnova SA, Deev AD, Karpov YuA. Arterial hypertension and ischemic heart disease in the actual prac- tice of a cardiologist. Cardiovascular Therapy and Prevention 2006; (1): 73-80. Russian (Шальнова С.А., Деев А.Д., Карпов Ю.А. Артериальная гипертония и ишемическая болезнь сердца в реальной практике врача-кардиолога. Кардиоваскулярная Терапия и Профилактика 2006; (1): 73-80).

15. Goncalves L.M. Left ventricular dysfunction and cytoprotection. Rev Port Cardiol 2000; 19 Suppl 5: V21-4.

16. Kowalski J., Pawlicki L., Baj Z. et al. Effect of trimetazidine on biological activity of neutrophils in patients with transient myocardial ischemia induced by exercise testing. Pol Merkuriusz Lek 2000; 9: 548-51.

17. Belardinelli R. Trimetazidine and the contractile response of dysfunctional myocardium in ischaemic cardiomyopathy. Rev Port Cardiol 2000; 19 (Suppl 5): V35-9.

18. Szwed H., Sadowski Z., Pachocki R. et al. The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients. A substudy from TRIMPOL-1. J Cardiovasc Drugs Ther 1999; 13: 217-22.