Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure

AIMS: The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. METHODS AND RESULTS: Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04+/-0.26 to 2.45+/-0.52 (P = 0.005), whereas EF (34+/-10 vs. 39+/-10%, P = 0.03) and METS (from 7.44+/-1.84 to 8.78+/-2.72, P = 0.03) increased. The mean cardiac PCr/ATP ratio was 1.35+/-0.33 with placebo, but was increased by 33% to 1.80+/-0.50 (P = 0.03) with trimetazidine. CONCLUSION: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels.