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European Heart Journal Advance Access published online on March 1, 2006

European Heart Journal, doi:10.1093/eurheartj/ehi816
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received August 11, 2005
Revised February 6, 2006
Accepted February 9, 2006

Clinical research

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

Gabriele Fragasso 1 *, Gianluca Perseghin 2, Francesco De Cobelli 3, Antonio Esposito 3, Altin Palloshi 1, Guido Lattuada 2, Paola Scifo 3, Giliola Calori 1, Alessandro Del Maschio 3, and Alberto Margonato 1

1 Department of Clinical Cardiology, Heart Failure Clinic, Istituto Scientifico/Universita' San Raffaele, Via Olgettina 60, 20132 Milano, Italy
2 Department of Internal Medicine, Section of Nutrition/Metabolism, Istituto Scientifico/Universita' San Raffaele, Milano, Italy
3 Department of Radiology, Istituto Scientifico/Universita' San Raffaele, Milano, Italy

* To whom correspondence should be addressed.
Gabriele Fragasso, E-mail: gabriele.fragasso{at}hsr.it


   Abstract

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.

Keywords: Heart failure; Trimetazidine; Magnetic resonance spectroscopy; Myocardial energetics; Left ventricular function.
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