European Heart Journal Advance Access originally published online on March 1, 2006
European Heart Journal 2006 27(8):942-948; doi:10.1093/eurheartj/ehi816
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Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure
1Department of Clinical Cardiology, Heart Failure Clinic, Istituto Scientifico/Universita' San Raffaele, Via Olgettina 60, 20132 Milano, Italy
2Department of Internal Medicine, Section of Nutrition/Metabolism, Istituto Scientifico/Universita' San Raffaele, Milano, Italy
3Department of Radiology, Istituto Scientifico/Universita' San Raffaele, Milano, Italy
Received 11 August 2005; revised 6 February 2006; accepted 9 February 2006; online publish-ahead-of-print 1 March 2006.
* Corresponding author. Tel: +39 02 26437366; fax: +39 02 26437395. E-mail address: gabriele.fragasso{at}hsr.it
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.
Key Words: Heart failure • Trimetazidine • Magnetic resonance spectroscopy • Myocardial energetics • Left ventricular function
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