New insights into the beneficial electrophysiologic profile of ranolazine in heart failure: Prevention of ventricular fibrillation with increased postrepolarization refractoriness and without drug-induced proarrhythmia

Journal of Cardiac Failure

Volumn 18, Issue 12, 2012, Pages 939-949

  Frommeyer, Gerrit ^a   Rajamani, Sridharan ^b   Grundmann, Fabian ^a   Stypmann, Jörg ^a   Osada, Nani ^c   Breithardt, Günter ^a   Belardinelli, Luiz ^b   Eckardt, Lars ^a   Milberg, Peter ^a  

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^b Gilead Sciences ^*  (United States)

^c UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

action potential prolongation; Chronic heart failure; drug induced proarrhythmia; postrepolarization refractoriness

Indexed keywords

RANOLAZINE; SOTALOL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIARRHYTHMIC ACTIVITY; ARTICLE; BRADYCARDIA; CONTROLLED STUDY; EX VIVO STUDY; EXPERIMENTAL RABBIT; FEMALE; HEART EJECTION FRACTION; HEART FAILURE; HEART MUSCLE POTENTIAL; HEART MUSCLE REFRACTORY PERIOD; HEART PROARRHYTHMIA; HEART REPOLARIZATION; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE PACING; HEART VENTRICLE TACHYCARDIA; ISOLATED HEART; NONHUMAN; PRIORITY JOURNAL; QT PROLONGATION; SHAM PROCEDURE;

ACETANILIDES; ACTION POTENTIALS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; DISEASE MODELS, ANIMAL; ELECTROCARDIOGRAPHY; HEART FAILURE; PIPERAZINES; RABBITS; REFRACTORY PERIOD, ELECTROPHYSIOLOGICAL; SOTALOL; VENTRICULAR FIBRILLATION;

EID: 84870567980     PISSN: 10719164     EISSN: 15328414     Source Type: Journal    
DOI: 10.1016/j.cardfail.2012.10.017     Document Type: Article

References (46)

1. G. Antoons, A. Oros, J.D. Beekman, M.A. Engelen, M.J. Houtman, and L. Belardinelli Late Na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model J Am Coll Cardiol 55 2010 801 809
2. A.K. Dhalla, W.Q. Wang, J. Dow, J.C. Shryock, L. Belardinelli, and A. Bhandari Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion Am J Physiol Heart Circ Physiol 297 2009 H1923 H1929
3. A.J. Moss, W. Zareba, K.Q. Schwarz, S. Rosero, S. McNitt, and J.L. Robinson Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome J Cardiovasc Electrophysiol 19 2008 1289 1293
4. S. Fredj, K.J. Sampson, H. Liu, and R.S. Kass Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action Br J Pharmacol 148 2006 16 24
5. C. Antzelevitch, L. Belardinelli, A.C. Zygmunt, A. Burashnikov, J.M. di Diego, and J.M. Fish Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties Circulation 110 2004 904 910
6. B.M. Scirica, D.A. Morrow, H. Hod, S.A. Murphy, L. Belardinelli, and C.M. Hedgepeth Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial Circulation 116 2007 1647 1652
7. N. Morita, J.H. Lee, Y. Xie, A. Sovari, Z. Qu, and J.N. Weiss Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine J Am Coll Cardiol 57 2011 366 375
8. P. Milberg, E. Hilker, S. Ramtin, Y. Cakir, J. Stypmann, and M.A. Engelen Proarrhythmia as a class effect of quinolones: increased dispersion of repolarization and triangulation of action potential predict torsades de pointes J Cardiovasc Electrophysiol 18 2007 647 654
9. P. Milberg, G. Frommeyer, A. Kleideiter, A. Fischer, N. Osada, and G. Breithardt Antiarrhythmic effects of free polyunsaturated fatty acids in an experimental model of LQT2 and LQT3 due to suppression of early afterdepolarizations and reduction of spatial and temporal dispersion of repolarization Heart Rhythm 8 2011 1492 1500
10. G. Frommeyer, P. Milberg, P. Witte, J. Stypmann, M. Koopmann, and M. Lucke A new mechanism preventing proarrhythmia in chronic heart failure: rapid phase-III repolarization explains the low proarrhythmic potential of amiodarone in contrast to sotalol in a model of pacing-induced heart failure Eur J Heart Fail 13 2011 1060 1069
11. 2+ exchanger suppresses torsades de pointes in an intact heart model of long QT syndrome-2 and long QT syndrome-3 Heart Rhythm 5 2008 1444 1452
12. G. Schram, L. Zhang, K. Derakhchan, J.R. Ehrlich, L. Belardinelli, and S. Nattel Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects Br J Pharmacol 142 2004 1300 1308
13. P. Milberg, M. Fink, C. Pott, G. Frommeyer, J. Biertz, and N. Osada I(Ca) block leads to suppression of early afterdepolarizations and reduction of transmural dispersion of repolarization in a whole heart model of chronic heart failure Br J Pharmacol 166 2012 557 568
14. P. Milberg, L. Eckardt, H.J. Bruns, J. Biertz, S. Ramtin, and N. Reinsch Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes J Pharmacol Exp Ther 303 2002 218 225
15. P. Milberg, R. Tegelkamp, N. Osada, R. Schimpf, C. Wolpert, and G. Breithardt Reduction of dispersion of repolarization and prolongation of postrepolarization refractoriness explain the antiarrhythmic effects of quinidine in a model of short QT syndrome J Cardiovasc Electrophysiol 18 2007 658 664
16. T. Yang, and D.M. Roden Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence Circulation 93 1996 407 411
17. L. Eckardt, W. Haverkamp, M. Borggrefe, and G. Breithardt Experimental models of torsades de pointes Cardiovasc Res 39 1998 178 193
18. K. Kumar, B.D. Nearing, C.R. Bartoli, K.F. Kwaku, L. Belardinelli, and R.L. Verrier Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart J Cardiovasc Electrophysiol 19 2008 1073 1079
19. P. Milberg, C. Pott, G. Frommeyer, M. Fink, M. Ruhe, and T. Matsuda Acute inhibition of the Na(+)/Ca(2+) exchanger reduces proarrhythmia in an experimental model of chronic heart failure Heart Rhythm 9 2012 570 578
20. L.M. Hondeghem, L. Carlsson, and G. Duker Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic Circulation 103 2001 2004 2013
21. M. Brennan, M. Palaniswami, and P. Kamen Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators Am J Physiol Heart Circ Physiol 283 2002 H1873 H1886
22. C. Antzelevitch, A. Burashnikov, S. Sicouri, and L. Belardinelli Electrophysiologic basis for the antiarrhythmic actions of ranolazine Heart Rhythm 8 2011 1281 1290
23. S. Sossalla, U. Maurer, H. Schotola, N. Hartmann, M. Didie, and W.H. Zimmermann Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIdelta(C) can be reversed by inhibition of late Na(+) current Basic Res Cardiol 106 2011 263 272
24. S. Rajamani, N. El-Bizri, J.C. Shryock, J.C. Makielski, and L. Belardinelli Use-dependent block of cardiac late Na(+) current by ranolazine Heart Rhythm 6 2009 1625 1631
25. P. Milberg, N. Reinsch, K. Wasmer, G. Mönnig, J. Stypmann, and N. Osada Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3 Cardiovasc Res 65 2005 397 404
26. P. Kirchhof, H. Degen, M.R. Franz, L. Eckardt, L. Fabritz, and P. Milberg Amiodarone-induced postrepolarization refractoriness suppresses induction of ventricular fibrillation J Pharmacol Exp Ther 305 2003 257 263
27. P.F. Kirchhof, C.L. Fabritz, and M.R. Franz Postrepolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects Circulation 97 1998 2567 2574
28. M.J. Koren, M.R. Crager, and M. Sweeney Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE) J Am Coll Cardiol 49 2007 1027 1034
29. A.L. Waldo, A.J. Camm, H. deRuyter, P.L. Friedman, D.J. MacNeil, J.F. Pauls SWORD Investigators Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Survival With Oral d-Sotalol Lancet 348 1996 7 12
30. D.M. Roden, R.L. Woosley, and R.K. Primm Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care Am Heart J 111 1986 1088 1093
31. D.S. Echt, P.R. Liebson, L.B. Mitchell, R.W. Peters, D. Obias-Manno, and A.H. Barker Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial N Engl J Med 324 1991 781 788
32. B.R. Chaitman, S.L. Skettino, J.O. Parker, P. Hanley, J. Meluzin, and J. Kuch Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina J Am Coll Cardiol 43 2004 1375 1382
33. L. Wu, J.C. Shryock, Y. Song, Y. Li, C. Antzelevitch, and L. Belardinelli Antiarrhythmic effects of ranolazine in a guinea pig in vitro model of long-QT syndrome J Pharmacol Exp Ther 310 2004 599 605
34. Kr inhibition on ventricular repolarization Circulation 123 2011 1713 1720
35. Y. Tsuji, T. Opthof, K. Kamiya, K. Yasui, W. Liu, and Z. Lu Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle Cardiovasc Res 48 2000 300 309
36. L. Vecchia, R. Ometto, G. Finocchi, and M. Vincenzi Torsade de pointes ventricular tachycardia during low dose intermittent dobutamine treatment in a patient with dilated cardiomyopathy and congestive heart failure Pacing Clin Electrophysiol 22 1999 397 399
37. C.R. Valdivia, W.W. Chu, J. Pu, J.D. Foell, R.A. Haworth, and M.R. Wolff Increased late sodium current in myocytes from a canine heart failure model and from failing human heart J Mol Cell Cardiol 38 2005 475 483
38. C. Antzelevitch Drug-induced spatial dispersion of repolarization Cardiol J 15 2008 100 121
39. S.C. Verduyn, M.A. Vos, J. van der Zande, F.F. van der Hulst, and H.J. Wellens Role of interventricular dispersion of repolarization in acquired torsades-de-pointes arrhythmias: reversal by magnesium Cardiovasc Res 34 1997 453 463
40. M.B. Thomsen, S.C. Verduyn, M. Stengl, J.D. Beekman, P.G. de, and O.J. van Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs Circulation 110 2004 2453 2459
41. A.I. Undrovinas, L. Belardinelli, N.A. Undrovinas, and H.N. Sabbah Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current J Cardiovasc Electrophysiol 17 Suppl 1 2006 S169 S177
42. M.B. Thomsen, P.G. Volders, J.D. Beekman, J. Matz, and M.A. Vos Beat-to-beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced torsades de pointes J Am Coll Cardiol 48 2006 1268 1276
43. M.A. Habbab, and N. el-Sherif Drug-induced torsades de pointes: role of early afterdepolarizations and dispersion of repolarization Am J Med 89 1990 241 246
44. G.X. Yan, W. Shimizu, and C. Antzelevitch Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations Circulation 98 1998 1921 1927
45. D.K. Murdock, M. Kersten, J. Kaliebe, and G. Larrain The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a review of experience with implications for possible "pill in the pocket" approach to atrial fibrillation Indian Pacing Electrophysiol J 9 2009 260 267
46. T.J. Bunch, S. Mahapatra, D. Murdock, J. Molden, J.P. Weiss, and H.T. May Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks Pacing Clin Electrophysiol 34 2011 1600 1606