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


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.


CONCLUSIONS
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.
Fragasso
Gabriele
G
Department of Clinical Cardiology, Heart Failure Clinic, Istituto Scientifico/Universita' San Raffaele, Via Olgettina 60, 20132 Milano, Italy. gabriele.fragasso@hsr.it
Perseghin
Gianluca
G
De Cobelli
Francesco
F
Esposito
Antonio
A
Palloshi
Altin
A
Lattuada
Guido
G
Scifo
Paola
P
Calori
Giliola
G
Del Maschio
Alessandro
A
Margonato
Alberto
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D011446:Prospective Studies; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D014665:Vasodilator Agents; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D014292:Trimetazidine