The effects of trimetazidine on heart rate variability in patients with slow coronary artery flow

Objective: We sought to examine the effect of trimetazidine (TMZ) on heart rate variability (HRV), endothelin-1 (ET-1), NO, and anginal symptoms in patients with slow coronary artery flow (SCAF). Methods: The 48 patients with SCAF (29 women and 19 men; mean age, 52 +/- 9 years) were included in the study. Twenty milligrams TMZ 3 times a day or matched placebo were given randomly in a double-blinded fashion for 4 weeks. Patients were divided into 4 groups as follows: exercise-positive, TMZ-given group (group A, n = 12); exercise-positive, placebo-given group (group B, n = 12); exercise-negative, TMZ-given group (group C, n = 12); and exercise-negative, placebo-given group (group D, n = 12). Results: After TMZ treatment, HRV parameters, including SD of the all R-R intervals, SD of the averages of R-R intervals in all 5-minute segments of the entire recording, percentage of R-R intervals with more than 50-millisecond variation, and the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, significantly improved both in exercise-positive and exercise-negative groups when compared with baseline. After TMZ treatment, ET-1 and NO levels significantly altered both in exercise-positive and exercise-negative groups when compared with baseline (17.7 +/- 2.7 vs 13.9 +/- 2.8 pg/mL [P = .01] and 18.1 +/- 3.8 vs 14.2 +/- 2.6 pg/mL [P = .01], respectively). After TMZ treatment, NO levels significantly increased in both exercise-positive and exercise-negative groups when compared with baseline (36.4 +/- 5.4 vs 43.3 +/- 6.8 pmol/L [P = .01] and 36.8 +/- 7.8 vs 43.3 +/- 4.8 mu mol/L [P = .01], respectively). However, in placebo group, neither HRV parameters nor ET-1 and NO levels altered when compared with baseline. Also, after treatment, a significant correlation was detected between HRV parameters, including SID of the averages of R-R intervals in all 5-minute segments of the entire recording, SID of the all R-R intervals, percentage of R-R. intervals with more than 50-millisecond variation, and the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, and NO and ET-1 levels in TMZ group but not placebo. Conclusion: Short-term TMZ therapy improved HRV parameters and endothelial products such as ETLI and NO as well as anginal symptom in patients with SCAR Improvement in HRV parameters was correlated with ET-1 and NO levels. (c) 2006 Elsevier Inc. All rights reserved.