Improved left and right ventricular functions with trimetazidine in patients with heart failure: a tissue Doppler study

Abstract

Downregulation of glucose and fatty acid oxidation occurs in heart failure (HF). Trimetazidine reduces fatty acid oxidation and increases glucose oxidation. In this single-blind study, trimetazidine, 20 mg three times per day (n = 51) or placebo (n = 36) was added to treatment of 87 HF patients receiving optimal HF therapy. Etiology of heart failure was coronary artery disease in 35 patients (68.6%) in the trimetazidine group and 22 (62.9%) in the placebo group. Fourteen (27.5%) patients in the trimetazidine group and 11 (31.4%) patients in the placebo group had diabetes. Peak systolic velocity (Vs), and the peak early diastolic (Vd) and late diastolic (Va) velocities of various segments left and right ventricles (RV) were obtained with tissue Doppler imaging (TDI) and averaged. Patients were re-evaluated three months later. Significant increases in mean left ventricular ejection fraction (LVEF) (33.3% +/- 5.6% to 42.4% +/- 6.3%, P < 0.001 and 30.6% +/- 8.2% to 33.2% +/- 6.6%, P = 0.021) and LV and RV myocardial velocities and mitral and tricuspid annular TDI velocities were observed in both groups. However, compared to placebo, increments in LVEF (9.1% +/- 4.2% vs. 2.5% +/- 1.4%, P < 0.001) and myocardial velocities were significantly higher with trimetazidine (P < 0.001 for LV Vs, Vd, Va; P = 0.035 for RV Vd; and P < 0.001 for RV Va and Vs). Increase in LVEF with trimetazidine was significantly correlated with presence of diabetes (r = 0.524, P < 0.001). With trimetazidine LVEF increased significantly more in diabetic patients compared to nondiabetics (P < 0.001). Also, patients having both diabetes and ischemic HF tended to have greater improvement in LVEF compared to ischemic HF patients without diabetes (P = 0.063). Addition of trimetazidine to current treatment of HF, especially for those who are diabetic, may improve LV and RV functions.

Trimetazidine: a meta-analysis of randomised controlled trials in heart failure

“…The trial and patient characteristics are shown in tables 2 and 3, respectively. Reports of 16 trials21 23–37 described an evaluation of LVEF (n=866), 1021 23–25 27 28 30 33 34 37 LVESV and LVEDV (n=491), six23 27 28 33 35 37 exercise capacity (exercise duration) (n=381), seven21 22 26 27 29 30 37 NYHA classification (n=426), four26 27 29 35 all-cause mortality (n=376) and four24 26 27 30 cardiovascular events and hospitalisation (n=189) during the study periods. Trimetazidine dosage ranged from 60 to 70 mg/day and treatment periods from 4 weeks to 24 months.…”

“…This indicates that trimetazidine may improve cardiac function even with the concomitant use of current standard therapies. Trimetazidine was recently found to have cardioprotective effects in patients with HF of different aetiologies other than ischaemic HF 21 24 27. We pooled the results for LVEF from three trials of non-ischaemic HF in response to trimetazidine treatment and showed a significant improvement (8.72%) of LVEF with trimetazidine.…”

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model

“…For example, the partial FA oxidation inhibitor trimetazidine directly acts on FA oxidation but indirectly improves carbohydrate metabolism in HF patients (49). Similar to the effects of NMN in the FXN-KO heart, trimetazidine improves LV systolic function, elevates the cardiac PCr/ATP ratio, and decreases cellular acidosis in human patients with congestive or ischemic failing hearts (37,(50)(51)(52)(53). These effects are achieved by a global reduction in resting EE with a concomitant whole-body and cardiac decrease in FA oxidation and increase in glucose oxidation (37,50,53).…”

Atualização da diretriz brasileira de insuficiência cardíaca crônica - 2012

“…Estudos com inclusão de pequeno número de pacientes demonstram benefício na IC com melhora na classe funcional, fração de ejeção, tolerância ao exercício ou diminuindo a mortalidade por todas as causas e hospitalização por IC [142][143][144][145][146][147] . Metanálise encontrou aumento da FEVE, redução da mortalidade por todas as causas e redução de eventos cardiovasculares ou hospitalização 148 .…”