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Trimetazidine improves Left Ventricular Ejection Fraction and Global Longitudinal Strain in patients with ischemic heart disease and reduced Ejection Fraction.

LVEF to evaluate Left Ventricular contractility has limitations, including the determination of suboptimal endocardial margins and extensive wall motion abnormalities. Indeed, the complexity of LV's contractile function is unlikely to be comprehensively represented only by the LVEF assessment.1 Recent data have demonstrated that LV Global Longitudinal Strain is a more sensitive marker for systolic dysfunction and contractility and provides incremental prognostic information when compared with LV ejection fraction1.

GLS is a new noninvasive method of ultrasound imaging with quantitative and objective capabilities to assess the global and regional functions of the cardiac myocardium. It detects early changes in myocardial contractile function and is a predictor of mortality and morbidity of patients with HFrEF with ischemic heart diseases.1

A 2022 randomized controlled clinical trial2 examined for the first time whether trimetazidine could improve left ventricular Global Longitudinal Strain (GLS) that represents LV contractile function, in addition to Ejection Fraction (EF) in patients with ischemic heart disease (IHD). Left Ventricular Ejection Fraction is a routine measure of left ventricular systolic function and has played a critical role in the risk stratification of patients with IHD.

Stable IHD patients were given trimetazidine or placebo for 3 months in addition to their usual treatments. Baseline values for LV ejection fraction (LVEF) were 34.6% ± 4.4%, and 7.4% ± 2.1% for GLS, and were similar in the 2 groups. Left Ventricular systolic functions including GLS and EF values were assessed again after 3 months using echocardiography.

There was a significant increase in the parameters of early and late systolic function in the trimetazidine group, which included LVEF and GLS whereas there was no significant difference in the control group.

In the Trimetazidine group, there were significant increases in the LV GLS by +1.5% (from − 6.9% ± 2.4% to − 8.4% ± 2.6%, p = 0.001) and mean LVEF values increased significantly by +7% (from the pre-value of 33.3% ± 4.9% to 40.3% ± 5.5% (p = 0.005)). 1

Previous trials have repeatedly demonstrated LVEF improvement with trimetazidine in IHD patients. The Bo hu & al3 metanalysis of 11 trials confirmed the beneficial effect of Trimetazidine with an improvement of +7% of the LV function versus placebo (p = 0.005). 2 Gao metanalysis, through 17 randomized clinical trials, reported a LVEF improvement by +7.37% vs placebo (p<0.01).4

For the first time, in addition to the known effect of trimetazidine on EF, this study demonstrated that trimetazidine improves LVGLS, a proof of increased contractility, in patients with ischemic heart disease and reduced ejection fraction. This beneficial effect with prognostical implication reinforces the medical interest in improving heart metabolism:5 Trimetazidine improves ATP production by 33% in cardiac cells, thereby, improving cardiac contractility, which is reflected by this improvement in LVGLS1,5.

SCAC-08/22-DM-173-VAS. For healthcare professional use only.
1.Harjoko. Trimetazidine improves left ventricular global longitudinal strain value in patients with heart failure with reduced ejection fraction due to ischemic heart disease. Drug Discoveries & Therapeutics. 2022; 16⁴:177-184.
2. Ng AC, Delgado V, Bertini M, Antoni ML, van Bommel RJ, van Rijnsoever EP, van der Kley F, Ewe SH, Witkowski T, Auger D, et al.Alterations in multidirectional myocardial functions in patients with aortic stenosis and preserved ejection fraction: a two-dimensional speckle tracking analysis.Eur Heart J. 2011; 32:1542–1550. doi: 10.1093/eurheartj/ehr084
3. Bo. Hu. Evaluation of trimetazidine in angina pectoris by echocardiography and radionuclide angiography: a meta-analysis of randomized, controlled trials. Clin Cardiol . 2011 Jun;34⁶:395-400
4. Gao. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011 Feb;97⁴:278-86
5.Fragasso et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine adenosine triphosphate ratio in patients with heart failure, European Heart Journal (2006) 27, 942
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