Int J Angiol
DOI: 10.1055/s-0036-1584880
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Ranolazine is an Effective and Safe Treatment of Adults with Symptomatic Premature Ventricular Contractions due to Triggered Ectopy

G. L. Murray
1   Department of Cardiovascular Research, Heart and Vascular Institute, Germantown, Tennessee
› Author Affiliations
Further Information

Publication History

Publication Date:
16 July 2016 (online)


Early and delayed afterdepolarizations (EAD/DAD) cause triggered ventricular ectopy. Because ranolazine (RAN) suppresses EAD/DAD, we postulated that RAN might be effective in reducing premature ventricular contractions (PVCs).

To assess the effect of RAN in patients with symptomatic PVCs due to triggered ectopy and its safety and tolerability.

A total of 59 patients with symptomatic PVCs were identified from full-disclosure Holters. Doses of 500 and 1,000 mg offlabel RAN, daily, were given to 34 and 66% patients, respectively, and repeat Holters were performed prospectively during mean followup of 3.1 months. The two Holters were retrospectively compared. Congestive heart failure (CHF) was defined as symptoms including dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and fatigue, with a brain natriuretic peptide > 400. Systolic (heart failure with reduced ejection fraction) versus diastolic (heart failure with preserved ejection fraction, HFpEF) CHF depended upon an echocardiographic left ventricular ejection fraction (LVEF) at least 50% by apical two- and four-chamber Simpson's method (HFpEF).

The mean age of the patients was 63 years, 60% were males, mean left ventricular ejection fraction was 60%, with 34% having coronary artery disease, 73% were hypertensive, 24% had type 2 diabetic, and 34% were on beta blockers. Upon repeat Holters at a mean of 3.1 months after initiating RAN, 95% (56/59) of the patients had their PVC count reduced as follows: 24% (14/59) had more than 90% decrease, 34% (20/59) had 71 to 90% decrease, and 17% (10/59) had 50 to 70% decrease. In the entire group, RAN reduced PVCs by 71% (mean: 13,329 to 3,837; p < 0.001). Ventricular bigeminy was reduced by 80% (4,168 to 851; p < 0.001), ventricular coupletswere reduced by 78% (374 to 81; p < 0.001), and ventricular tachycardiawas reduced by 91% (56 to 5; p < 0.001). The PVC reduction was dose dependent.

Off-label RAN offers an effective and safe pharmacologic treatment for symptomatic triggered PVCs. A large, prospective randomized study is needed.


This is the only article ever written on this subject.

  • References

  • 1 Antzelevitch C, Belardinelli L, Zygmunt AC , et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004; 110 (8) 904-910
  • 2 Belardinelli L, Giles W, Rajamani S , et al. Cardiac Late Na+ current: proarrhythmic effects, roles in long QT syndromes, and pathological relationship to CaMKII and oxidative stress. Heart Rhythm 2015; 12 (2) 440-448
  • 3 Lindegger N, Hagen BM, Marks AR, Lederer WJ, Kass RS. Diastolic transient inward current in long QT syndrome type 3 is caused by Ca2+ overload and inhibited by ranolazine. J Mol Cell Cardiol 2009; 47 (2) 326-334
  • 4 Antoons G, Oros A, Beekman JD , et al. Late Na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol 2010; 55 (8) 801-809
  • 5 Fozzard HA. Afterdepolarizations and triggered activity. Basic Res Cardiol 1992; 87 (Suppl. 02) 105-113
  • 6 Xie LH, Weiss JN. Arrhythmogenic consequences of intracellular calcium waves. Am J Physiol Heart Circ Physiol 2009; 297 (3) H997-H1002
  • 7 Li P, Rudy Y. A model of canine Purkinje cell electrophysiology and Ca(2+) cycling: rate dependence, triggered activity, and comparison to ventricular myocytes. Circ Res 2011; 109 (1) 71-79
  • 8 Janse MJ. Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc Res 2004; 61 (2) 208-217
  • 9 Kujala K, Paavola J, Lahti A , et al. Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early and delayed afterdepolarizations. PLoS ONE 2012; 7 (9) e44660
  • 10 Wolk R. Arrhythmogenic mechanisms in left ventricular hypertrophy. Europace 2000; 2 (3) 216-223
  • 11 Wolk R. Arrhythmogenic mechanisms in left ventricular hypertrophy. Europace 2000; 2 (3) 216-223
  • 12 Shimizu W, Ohe T, Kurita T , et al. Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome. J Am Coll Cardiol 1995; 26 (5) 1299-1309
  • 13 Kimura S, Bassett AL, Xi H, Myerburg RJ. Early afterdepolarizations and triggered activity induced by cocaine. A possible mechanism of cocaine arrhythmogenesis. Circulation 1992; 85 (6) 2227-2235
  • 14 Katz L, Pick A. Clinical Electrophysiology, Part 1: The Arrhythmias. Philadelphia, PA: Lea & Feibinger; 1956: 224-226
  • 15 Chung E. Diagnosis and clinical significance of parasystole. In Sando E, Fleasted-Jensen E, Olesen K. eds. Symposium on Cardiac Arrhythmias. Sodertaje, Sweden: AB Astra; 1970: 271-294
  • 16 Scirica BM, Braunwald E, Belardinelli L , et al. Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations 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 2010; 122 (5) 455-462
  • 17 Castellanos A, Sandudi N, Myerberg R. Parasystole. In Zipes D, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 3rd ed. Philadelphia, PA: WB Saunders; 2000: 690-695
  • 18 Lipnitskiĭ TN, Denisiuk VI, Kolesnik PF, Sizova MP, Ivanov VP, Stoliarchuk VA. The clinical efficacy of verapamil in ventricular extrasystolic arrhythmia and parasystole [in Russian]. Ter Arkh 1993; 65 (12) 42-44
  • 19 Tomcsányi J, Tenczer J, Horváth L. Effect of adenosine on ventricular parasystole. J Electrocardiol 1996; 29 (1) 61-63
  • 20 Zanini S, Rossi R. Ventricular parasystole: successful treatment with diphenylhydantoin [in Italian]. G Ital Cardiol 1972; 2 (4) 575-578
  • 21 Furuse A, Shindo G, Makuuchi H , et al. Apparent suppression of ventricular parasystole by cardiac pacing. Jpn Heart J 1979; 20 (6) 843-851
  • 22 Paleev NR, Kel'man IM, Kovaleva LI, Nikiforova TB, Gurevich MA. Cordarone treatment of parasystole [in Russian]. Kardiologiia 1980; 20 (4) 19-21
  • 23 Saad M, Mahmoud A, Elgendy IY, Richard Conti C. Ranolazine in cardiac arrhythmia. Clin Cardiol 2016; 39 (3) 170-178
  • 24 Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006; 113 (20) 2462-2472
  • 25 Morita N, Lee JH, Xie Y , et al. Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine. J Am Coll Cardiol 2011; 57 (3) 366-375
  • 26 Gaur N, Rudy Y, Hool L. Contributions of ion channel currents to ventricular action potential changes and induction of early afterdepolarizations during acute hypoxia. Circ Res 2009; 105 (12) 1196-1203
  • 27 Xie LH, Chen F, Karagueuzian HS, Weiss JN. Oxidative-stress-induced afterdepolarizations and calmodulin kinase II signaling. Circ Res 2009; 104 (1) 79-86
  • 28 Song Y, Shryock JC, Wagner S, Maier LS, Belardinelli L. Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther 2006; 318 (1) 214-222