Skip to main content
SpringerLink
Log in

Metabolic Management of Coronary Heart Disease: Adjunctive Treatment with Trimetazidine Decreases QT Dispersion in Patients with a First Acute Myocardial Infarction

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose. The metabolic management of ischemic heart disease represents a promising new therapeutic approach for acute coronary syndromes. Trimetazidine has been suggested to exert anti-ischemic properties on myocardium without affecting myocardial oxygen consumption or supply. The aim of this study was to investigate whether the administration of trimetazidine, as an adjunct to conventional treatment, decreases QT dispersion in patients with acute myocardial infarction (AMI).

Methods and results. The study was prospective, randomized, double-blind and included 55 out of 86 consecutive patients aged ≤80 years, admitted with a first AMI. Excluded from the study subjects with atrial fibrillation or pacing-rhythm, bundle branch block, pericardial or valvular heart disease or cardiogenic shock. Also were excluded patients treated with inotropic and antiarrhythmic agents, except for beta blockers. Enrolled patients were randomized into 2 groups: Trimetazidine group (n = 29) and control group (n = 26). All patients were treated conventionally and, in addition, trimetazidine group patients were received trimetazidine 20 mg orally every 8 hours started after randomization and continued throughout hospitalization. The QT and QTc (corrected QT) dispersion were measured manually on 3 and 7 post-AMI days. The mean values of QT and QTc dispersion were significantly lower in trimetazidine group on both days, compared to control group: Day 3, QTD = 52 ± 24 ms vs 68 ± 30 ms (p = 0.034), QTcD = 52 ± 21 ms vs 75 ± 34 ms (p = 0.004). Day 7, QTD = 39 ± 17 ms vs 60 ± 20 ms (p < 0.0001), QTcD 40 ± 17 ms vs 62 ± 20 ms (p < 0.0001). Between days 3 and 7 the mean values of QT (p = 0.003) and QTc dispersion (p = 0.002) were decreased significantly only in trimetazidine group. An analysis with respect to the use of thrombolysis revealed that trimetazidine sub-groups had lower QT and QTc dispersion mean values on day 7, both in patients treated (p < 0.05) and non-treated (p = 0.001) with thrombolysis.

Conclusions. It is concluded that trimetazidine decreases QT and QTc dispersion after acute myocardial infarction. Further investigation is needed to evaluate the mechanism and the clinical implications of this effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zabel MR, Portnoy S, Franz MR. Electrocardiographic indexes of dispersion of ventricular repolarization: An isolated heart validation study. J Am Coll Cardiol 1995; 25: 746-752.

    PubMed  Google Scholar 

  2. Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol 2000; 36(6): 1749-1766.

    PubMed  Google Scholar 

  3. Day CP, McComb JM, Campbell RWF. QT dispersion: An indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990; 63: 342-344.

    PubMed  Google Scholar 

  4. Linker NJ, Colonna P, Kekwick CA, Till J, Camm J, Ward DE. Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes. Am J Cardiol 1992; 69: 634-638.

    PubMed  Google Scholar 

  5. Hii JTY, Wyse DG, Gillis AM, Duff HJ, Solylo MA, Mitchell LB. PrecordialQTinterval dispersion as a marker of torsade de pointes: Disparate effects of class Ia antiarrhythmic drugs and amiodarone. Circulation 1992; 86: 1376-1382.

    PubMed  Google Scholar 

  6. Glancy JM, Garratt CJ, de Bono DP. Dynamics of QT dispersion during myocardial infarction and ischaemia. Int J Cardiol 1996; 57(1): 55-60.

    PubMed  Google Scholar 

  7. Ciolli A, Di Lorenzo M, Bevilacqua U, et al. QT dispersion and early arrhythmic risk during acute myocardial infarction. G Ital Cardiol 1999; 29(12): 1438-1444.

    PubMed  Google Scholar 

  8. Perkiomaki JS, Koistinen MJ, Yli Mayry S, Huikuri HV. Dispersion of QT interval in patients with and without susceptibility to ventricular arrhythmias after previous myocardial infarction. J Am Coll Cardiol 1995; 26: 174-179.

    PubMed  Google Scholar 

  9. Moreno FLI, Teresa Villanueva Ma, Karagounis LA, Anderson JL, for the TEAM-2 Study Investigators. Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. Circulation 1994; 90: 94-100.

    PubMed  Google Scholar 

  10. Karagounis LA, Anderson JL, Moreno FL, Sorensen SG. Multivariate associates of QT dispersion in patients with acute myocardial infarction: Primacy of patency status of the infarct-related artery. TEAM-3 Investigators. Third trial of thrombolysis with eminase in acute myocardial infarction. Am Heart J 1998; 135(6, Pt. 1): 1027-1035.

    PubMed  Google Scholar 

  11. Sellier P, Audouin P, Payen B, Corona P, Duong TC, Ourbak P. Acute effects of trimetazidine evaluated by exercise testing. Eur J Clin Pharmacol 1987; 33: 205-207.

    PubMed  Google Scholar 

  12. Timour Q, Harpney C, Francoise D, Faucon C. Is the antianginal action of trimetazidine independent of hemodynamic changes. Cardiovasc Drugs Ther 1991; 5: 1043-1044.

    PubMed  Google Scholar 

  13. Kay L, Fineli C, Aussedat J, Guarnieri C, Rossi A. Improvement of long-term preservation of the isolated arrested rat heart by trimetazidine: Effects on the energy state and mitochondrial function. Am J Cardiol 1995; 76: 45B-49B.

    PubMed  Google Scholar 

  14. Lavanchy N, Martin J, Rossi A. Anti-ischemia effects of trimetazidine: 31P-NMR spectroscopy in the isolated rat heart. Arch Int Pharmacodyn Ther 1987; 286: 97-110.

    PubMed  Google Scholar 

  15. Maridonneau-Parini I, Harpey C. Effects of trimetazidine on membrane damage induced by oxygen free radicals in human red cells. Br J Clin Pharmacol 1985; 20: 148-151.

    PubMed  Google Scholar 

  16. Meneveau N, Khalife K, Louis JP, et al. Free radicals, thrombolytic therapy and myocardial infarction: Results of the EMIP-FR angiography substudy. Eur Heart J 1997; 18: 171.

    Google Scholar 

  17. Ozdemir R, Tuncer C, Aladag M, et al. Effect of trimetazidine on late potentials after acute myocardial infarction. Cardiovasc Drugs Ther 1999; 13(2): 145-149.

    PubMed  Google Scholar 

  18. Papadopoulos CL, Kanonidis IE, Kotridis PS, et al. The effect of trimetazidine on reperfusion arrhythmias in acute myocardial infarction. Int J Cardiol 1996; 55: 137-142.

    PubMed  Google Scholar 

  19. The EMIP-FR group. Effect of 48-h intravenous trimetazidine on short-and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial. European Heart Journal 2000; 21: 1537-1546.

    Google Scholar 

  20. Zabel M, Franz MR, Klingenheben T, et al. Ratedependence of QT dispersion and the QT interval: Comparison of atrial pacing and exercise testing. Journal of the American College of Cardiology 2000; 36(5): 1654-1658.

    PubMed  Google Scholar 

  21. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920; 7: 353-370.

    Google Scholar 

  22. Allibardi S, Chierchia SL, Cerioli V, et al. Trimetazidine reduces post-ischemic dysfunction in rat hearts by decreasing energy requirements during underperfusion. J Cardiovasc Pharmacol 1998; 12: 543-549.

    Google Scholar 

  23. Williams FM, Tanda K, Kus M, Williams TJ. Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits. J Cardiovasc Pharmacol 1993; 22: 828-833.

    PubMed  Google Scholar 

  24. Noble MI, Belcher PR, Drake-Holland AJ. Limitation of infarct size by trimetazidine in the rabbit. Am J Cardiol 1995; 76: 41B-44B.

    PubMed  Google Scholar 

  25. Lagadic-Gossman D, Le Prigent K, Feuvray D. Effect of trimetazidine on pHI regulation in the rat isolated ventricular myocytes. Br J Pharmacol 1996; 117: 831-837.

    PubMed  Google Scholar 

  26. Fantini E, Athias P, Demaison L, Grynberg A. Protective effects of trimetazidine on pHi regulation in hypoxic cardiac myocytes from the rat. Fundam Clin Pharmacol 1997; 11: 427-439.

    PubMed  Google Scholar 

  27. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580-588.

    PubMed  Google Scholar 

  28. Belcher PR, Drake-Holland AJ, Hynd JW, Noble MI. Effects of trimetazidine on in vivo coronary arterial platelet thrombosis. Cardiovasc Drugs Ther 1993; 7: 149-157.

    PubMed  Google Scholar 

  29. Stilli D, Aimi B, Sgoifo A, et al. Dependence of temporal variability of ventricular recovery on myocardial fibrosis. Role of mechanoelectrical feedback? Cardiovasc Res 1998; 37: 58-65.

    PubMed  Google Scholar 

  30. Naka M, Shiotani I, Koretsune Y, et al. Occurrence of sustained increase in QT dispersion following exercise in patients with residual myocardial ischemia after healing of anterior wall myocardial infarction. Am J Cardiol 1997; 80: 1528-1531.

    PubMed  Google Scholar 

  31. Kleiman RB, Houser SR. Outward currents in normal and hypertrophied feline ventricular myocytes. Am J Physiol 1989; 256: H1450-H1461.

    PubMed  Google Scholar 

  32. Yunus A, Gillis AM, Traboulsi M, et al. Effect of coronary angioplasty on precordial QT dispersion. AmJ Cardiol 1997; 79: 1339-1342.

    Google Scholar 

  33. Teragawa H, Hirao H, Muraoka Y, Yamagata T, Matsuura H, Kajiyama G. Relation between QT dispersion and adenosine triphosphate stress thallium-201 single-photon emission computed tomographic imaging for detecting myocardial ischemia and scar. Am J Cardiol 1999; 83: 1152-1156.

    PubMed  Google Scholar 

  34. Desideri A, Celegon L. Metabolic management of ischemic heart disease: Clinical data with trimetazidine. AmJ Cardiol 1998; 82(5A): 50K-53K.

    Google Scholar 

  35. Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P. Trimetazidine: A new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. Br J Clin Pharmacol 1994; 37: 279-288.

    PubMed  Google Scholar 

  36. Detry JM, Leclercq PJ. Trimetazidine European Multicenter Study versus propranolol in stable angina pectoris: Contribution of Holter electrocardiographic ambulatory monitoring. Am J Cardiol 1995; 76: 8B-11B.

    PubMed  Google Scholar 

  37. Sellier P. Chronic effects of trimetazidine on ergometric parameters in effort angina. Cardiovasc Drugs Ther 1990; 4(Suppl 4): 822-823.

    PubMed  Google Scholar 

  38. Kober G, Buck T, Sievert H, Vallbracht C. Myocardial protection during percutaneous transluminal coronary angioplasty: Effects of trimetazidine. Eur Heart J 1992; 13: 1109-1115.

    PubMed  Google Scholar 

  39. Van de Loo A, Arendts W, Hohnloser S. Variability of QT dispersion measurements in the surface electrocardiogram in patients with acute myocardial infarction and in normal subjects. Am J Cardiol 1994; 74: 1113-1118.

    PubMed  Google Scholar 

  40. Glancy JM, Garratt CJ, Woods KL, de Bono DP. QT dispersion and mortality after myocardial infarction. Lancet 1995; 345: 945-948.

    PubMed  Google Scholar 

  41. Zabel M, Klingenheben T, Franz MR, Hohnloser SH. Assessment of QT dispersion for prediction of mortality or arrhythmic events after myocardial infarction: Results of a prospective, long-term follow-up study. Circulation 1998; 97: 2543-2550.

    PubMed  Google Scholar 

  42. Pedretti RF, Catalano O, Ballardini L, de Bono DP, Radice E, Tramarine R. Prognosis in myocardial infarction survivors with left ventricular dysfunction is predicted by electrocardiographic RR interval but not QT dispersion. Int J Cardiol 1999; 68: 83-93.

    PubMed  Google Scholar 

  43. Puljevic D, Smalcelj A, Durakovic Z, Goldner V. The influence of atenolol and propafenone on QT interval dispersion in patients 3 months after myocardial infarction. Int J Clin Pharmacol Ther 1997; 35`(9): 381-384.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, District General Hospital of Ioannina, “G. Hatzikosta”, Ioannina, Greece

    Evaggelos Kountouris, Eugenia Pappa, Kostas Pappas, Vasiliki Dimitroula, Paulos Karanikis, Thomas Tzimas & Kostas Siogas

Authors
  1. Evaggelos Kountouris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eugenia Pappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kostas Pappas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vasiliki Dimitroula
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paulos Karanikis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas Tzimas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kostas Siogas
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kountouris, E., Pappa, E., Pappas, K. et al. Metabolic Management of Coronary Heart Disease: Adjunctive Treatment with Trimetazidine Decreases QT Dispersion in Patients with a First Acute Myocardial Infarction. Cardiovasc Drugs Ther 15, 315–321 (2001). https://doi.org/10.1023/A:1012706630965

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012706630965

Search

Navigation