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European Heart Journal Advance Access originally published online on April 24, 2007
European Heart Journal 2007 28(9):1102-1108; doi:10.1093/eurheartj/ehm071
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Trimetazidine improves endothelial dysfunction in chronic heart failure: an antioxidant effect

Romualdo Belardinelli*, Maridia Solenghi, Loretta Volpe and Augusto Purcaro

Cardiac Rehabilitation and Prevention Section, Lancisi Heart Institute, Via Conca 71, 60020 Torrette di Ancona, Italy

Received 8 July 2006; revised 28 February 2007; accepted 8 March 2007; online publish-ahead-of-print 24 April 2007.

* For correspondence. Tel: +32 0 71 596 5344; fax: +32 0 71 596 5402. E-mail address: r.belardinelli{at}ao-umbertoprimo.marche.it

Aims: To determine whether trimetazidine (TMZ) improves the endothelium-dependent relaxation (EDR) in chronic heart failure (CHF) and whether this effect is associated with its antioxidant properties.

Methods and results: We studied 51 patients (mean age 51.4 ± 6 years) with CHF secondary to ischaemic cardiomyopathy (ejection fraction 32.5 ± 4.5%). Plasma malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured from an antecubital vein on study entry and after a 4 week treatment with oral TMZ (20 mg tid) (group T, n = 23) or placebo (group C, n = 22) given randomly. Endothelium-dependent vasodilation of the radial artery (RA) was determined by intra-arterial infusion of acetylcholine (7.5, 15 and 30 µg/min). Patients receiving TMZ had an increased radial artery diameter (RAD) in response to each dose of acetylcholine infusion and a greater peak oxygen uptake (P < 0.01 vs. placebo). Plasma MDA and LOOHs levels were reduced at 4 weeks only in patients receiving TMZ (P < 0.001 for both vs. placebo). The improvement in ED-vasodilation was correlated with changes in peak VO2 (r = 0.68; P = 0.0001), MDA (r = –0.61; P = 0.0002) and LOOHs (r = –0.59; P = 0.005).

Conclusion: TMZ improves the ED-relaxation in patients with ischaemic cardiomyopathy. The antioxidant properties of TMZ may play a role.

Key Words: Trimetazidine • Chronic heart failure • Endothelial dysfunction • Oxidative stress


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