To access this material please log in or register

Register Authorize

Dynamics of sudden coronary death markers in patients with coronary heart disease and hypertension in combination with left ventricular hypertrophy against Ivabradine therapy

Koziolova N. A., Surovtseva M. V., Eltsova M. А.

Keywords: hypertension, sudden cardiac death, ivabradine, coronary heart disease

DOI: 10.18087/rhj.2012.2.1669

Relevance. Excessive ventricular ectopic activity, high HR at rest, values of daily average variability of a rhythm of heart and a dispersion of interval QT, systolic dysfunction of LV myocardium, LV hypertrophy (LVH) are considered as potential markers of sudden coronary death (SCD). Objective. Estimate dynamics of SCD markers in patients with CHD in combination with hypertension and LVH against therapy with Ivabradine as a part of a complex treatment. Materials and methods. The study included 90 patients with stable angina FC II–III in combination with AH and LVH. Depending on an anti-ischemic therapy, patients were into 3 equal groups: in the first group, patients took Perindoplyl and Ivabradine, in the second group, Perindoplyl, Bisopropol and Ivabradine, in the third group – Perindoplyl and Bisopropol. Duration of treatment was 6 months.Results. Inclusion of Ivabradine to the anti-ischemic therapy of patients with stable angina FC II–III in combination with AH and LVH had additional antianginal and anti-ischemic effect and provided suppression of ventricular ectopic activity, reduction of daily average HR, recourse of LV mass index, increase of LVEF and decrease in variability of heart rhythm, optimization myocardial collagenolysis and decrease of myocardial stress without change of QT interval, QTc and daily dispersion of QT interval. The maximum effect was observed at administration of three-component anti-ischemic therapy. Conclusion. Ivabradine in combination with or without a beta-blocker has not only anti-ischemic effect, but also favorably influences markers of sudden coronary death, without extending QT interval within 24 hours.
  1. Goldberger JJ, Cain ME, Hohnloser SH. еt al. American Heart Association / American College of Cardiology Foundation / Heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Circulation. 2008;118 (14):1497–1518.
  2. Adabag AS, Luepker RV, Roger VL, Gersh BJ. Sudden cardiac death: epidemiology and risk factors. Nat Rev Cardiol. 2010;7 (4):216–225.
  3. Bauer A, Barthel P, Schneider R et al. Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved left ventricular function (ISAR-Risk). Eur Heart J. 2009;30 (5):576–583.
  4. Diaz A, Bourassa M, Guertin M, Tardif JC. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J. 2005;26 (10):967–974.
  5. Lanza GA. The electrocardiogram as a prognostic tool for predicting major cardiac events. Prog Cardiovasc Dis. 2007;50 (2):87–111.
  6. Mauss O, Klingenheben T, Ptaszynski P, Hohnloser SH. Bedside risk stratification after acute myocardial infarction: prospective evaluation of the use of heart rate and left ventricular function. J Electrocardiol. 2005;38 (2):106–112.
  7. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996;17 (3):354–381.
  8. Panagiotakos DB, Kromhout D, Menotti A et al. The relation between pulse pressure and cardiovascular mortality in 12,763 middle-aged men from various parts of the world: a 25‑year follow-up of the seven countries study. Arch Intern Med. 2005;165 (18):2142–2147.
  9. Nieminen T, Verrier RL. Usefulness of T-wave alternans in sudden death risk stratification and guiding medical therapy. Ann Noninvasive Electrocardiol. 2010;15 (3):276–288.
  10. Nakajima K, Nakajima Y, Takeichi S, Fujita MQ. ApoB-100 carrying lipoprotein, but not apoB-48, is the major subset of proatherogenic remnant-like lipoprotein particles detected in plasma of sudden cardiac death cases. Atherosclerosis. 2007;194 (2):473–482.
  11. Sands SA, Reid KJ, Windsor SL, Harris WS. The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. Lipids. 2005;40 (4):343–347.
  12. John BT, Tamarappoo BK, Titus JL et al. Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death. Heart Rhythm. 2004;1 (2):141–149.
  13. Ten Tusscher KH, Panfilov AV. Influence of diffuse fibrosis on wave propagation in human ventricular tissue. Europace. 2007;9 (Suppl 6):vi38–45.
  14. Priori SG, Aliot E, Blomstrom-Lundqvist C et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J. 2001;22 (16):1374–1450.
  15. Fox K, Ford I, Steg PG et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372 (9641):807–816.
  16. Swedberg K, Komajda M, Bohm M et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376 (9744):875–885.
  17. Chobanian AN, Bakris GL, Black HR et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 2003;289 (19):2560–2572.
  18. Tavazzi L, Mugelli A. Can If inhibition help in congestive heart failure? Dial. Cardiovasc. Med 2006;11 (1): 30–35.
  19. Stilli D, Sgoifo A, Macchi E et al. Myocardial remodeling and arrhythmogenesis in moderate cardiac hypertrophy in rats. Am J Physiol Heart Circ Physiol. 2001;280 (1):H142–150.
  20. Biel M, Schneider A, Wahl C. Cardiac NCN channels: structure, function, and modulation. Trends Cardiovasc Med. 2002;12 (5):206–212.
  21. Koncz I, Szél T, Bitay M et al. Electrophysiological effects of ivabradine in dog and human cardiac preparations: potential antiarrhythmic actions. Eur J Pharmacol. 2011;668 (3):419–426.
  22. Riccioni G. Ivabradine: recent and potential applications in clinical practice. Expert Opin Pharmacother. 2011;12 (3):443–450.
  23. Ulu N, Henning RH, Goris M et al. Effects of ivabradine and metoprolol on cardiac angiogenesis and endothelial dysfunction in rats with heart failure. J Cardiovasc Pharmacol. 2009;53 (1):9–17.
  24. Milliez P, Messaoudi S, Nehme J et al. Beneficial effects of delayed ivabradine treatment on cardiac anatomical and electrical remodeling in rat severe chronic heart failure. Am J Physiol Heart Circ Physiol. 2009;296 (2):H435–441.
  25. Maczewski M, Mackiewicz U. Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart. Cardiovasc Res. 2008;79 (1):42–51.
  26. Mulder P, Barbier S, Chagraoui A et al. Long-term heart rate reduction induced by the selective I (f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation. 2004;109 (13):1674–1679.
  27. Bayes-Genis A, Vazquez R, Puig T et al. for the MUSIC Study Group. Left atrial enlargement and NT-proBNP as predictors of sudden cardiac death in patients with heart failure. Eur J Heart Fail. 2007;9 (8):802–807.
  28. Albert CM. N-terminal pro-B-type natriuretic peptide and sudden cardiac death risk: implications for primary prevention of sudden cardiac death. Heart Rhythm. 2011;8 (2):234–235.
  29. Custodis F, Baumhäkel M, Schlimmer N et al. Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2008;117 (18):2377–2387.
  30. Lopez-Bescos L, Filipova S, Martos R. Long-term safety and efficacy of ivabradine in patients with chronic stable angina. Cardiology. 2007;108 (4):387–396.
  31. Tardif JC, Camm J, Le Heuzey JY. The If current inhibitor ivabradine significantly increases heart rate variability compared with amlodipine in patients with chronic stable angina. Аbstracts Can Cardiolvasc.Cоngress 2006; № 686.
  32. Sarullo FM, Fazio G, Puccio D et al. Impact of ''off-label'' use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther. 2010;15 (4):349–355.
Koziolova N. A., Surovtseva M. V., Eltsova M. А. Dynamics of sudden coronary death markers in patients with coronary heart disease and hypertension in combination with left ventricular hypertrophy against Ivabradine therapy. Russian Heart Journal. 2012;11(2):83-88

To access this material please log in or register

Register Authorize
Ru En