Pharmacological and therapeutical basis of torsades de pointes

Chakradhar Thota, Vijayakrishna Pakanati, Shirisha Siddamshetty, Satyapriya Koppada, Swathi Patha


Torsades de pointes (TdP) is a specific form of polymorphic ventricular tachycardia, which is a dreadful condition, severity varies from mild asymptomatic condition to severe life threatening state. In this review, i would like to highlight the physiological, pathological and pharmacological causes, prevention and management of torsades de pointes. In this present world of therapeutic jungle, due to wide spread use of medication (poly pharmacy), there is a reasonable chance of getting drug interactions resulting in prolonged QTc interval leading to tosades de pointes. The main aim of this study is to bring awareness about risk of developing torsades de pointes in patients receiving multiple drugs and also to make clinicians and pharmacologists little more cautious while prescribing drugs.


ECG, QTc interval prolongation, TdP, Arrhythmias, Drugs

Full Text:



Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Archives desMaladies du Coeur et des Vaisseaux. 1966;59(2):263-72.

Motte G, Coumel P, Abitbol G, Dessertenne F, Slama R. The long QT syndrome and syncope caused by spike torsades. Arch Mal Coeur Vaiss. 1970;63:831-53.

Barbey JT, Lazzara R, Zipes DP. Review of spontaneous adverse event reports of serious ventricular arrhythmias QT prolongation, syncope, and sudden death in patients treated with cisapride. Circulation. 1999;100:I-308.

Wysowski DK, Corken A, Gallo-Torres H, Talarico L, Rodriguez EM. et al. Post-marketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and Food and Drug Administration regulatory actions. Am J Gastroenterol. 2001;96:1698-703.

Monahan BP, Ferguson CL, Killeavy ES, Lloyd BK, Troy J, Cantilena LR. Torsades de pointes occurring in association with terfenadine use. J Am Med Assoc. 1990;264:2788-90.

Nikolic G, Bishop RL, Singh JB. Sudden death recorded during Holter monitoring. Circulation. 1982;66(1):218-25.

Arya A. Gender-related differences in ventricular repolarization:beyond gonadal steroids. Journal of Cardiovascular Electrophysiology. 2005;16(5):525-7.

Xiao L, Xiao J, Luo X, Lin H, Wang Z, Nattel S. Feedback remodeling of cardiac potassium current expression: a novel potential mechanism for control of repolarization reserve. Circulation. 2008;118(10):983-92.

Yang T, Roden DM. Extracellular potassium modulation of drug block of IKr: implications for torsade de pointes and reverse use-dependence. Circulation. 1996;93(3):407-11.

Antzelevitch C, Sicouri S. Clinical relevance of cardiac arrhythmias generated by after depolarisation: role of M cells in the generation of U wave, triggered activity, and torsades de pointes. J Am Coll Cardiol. 1994;23:259-77.

Kirchhof P, Franz MR, Bardai A, Wilde AM. Giant T-U waves precede torsades de pointes in long QT syndrome: a systematic electrocardiographic analysis in patients with acquired and congenital QT prolongation. J Am Coll Cardiol. 2009;54(2):143-9.

Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, et al. Genetic variations of HCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. Journal of Molecular Medicine. 2004;82(3):182-8.

Mank-Seymour AR, Richmond JL, Wood LS, Reynolds JM, Fan YT, Warnes GR, et al. Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. American Heart Journal. 2006;152(6):1116-22.

Jost N, Virág L, Bitay M, Takács J, Lengyel C, Biliczki P, et al. Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle. Circulation. 2005;112:1392-9.

Habuchi Y, Tanaka H, Furukawa T, Tsujimura Y, Takahashi H, Yoshimura M. Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes. American Journal of Physiology Heart and Circulatory Physiology. 1992;262(2):345-54.

Fitzgerald PT, Ackerman MJ. Drug-induced torsades de pointes: the evolving role of pharmacogenetics. Heart Rhythm. 2005;2(11):S30-S37.

Sadanaga T, Sadanaga F, Yao H, Fujishima M. An evaluation of ECG leads used to assess QT prolongation. Cardiology. 2006;105(3):149-54.

Morganroth J, Brozovich FV, McDonald JT, Jacobs RA. Variability of the QT measurement in healthy men, with implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia. American Journal of Cardiology. 1991;67(8):774-6.

Molnar J, Zhang F, Weiss J, Ehlert FA, Rosenthal JE. Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events. Journal of the American College of Cardiology. 1996;27(1):76-83.

Reardon M, Malik M. QT interval change with age in an overtly healthy older population. Clinical Cardiology. 1996;19(12):949-52.

Indik JH, Pearson EC, Fried K, Woosley RL. Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm. 2006;3(9):1003-7.

Etheridge SP, Compton SJ, Tristani-Firouzi M, Mason JW. A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. Journal of the American College of Cardiology. 2003;42(10):1777-82.

Roden DM. Risks and benefits of antiarrhythmic therapy. N Engl J Med. 1994;331:785-91.

Welch R, Chue P. Antipsychotic agents and QT changes. J Psychiatry Neurosci. 2000;25:154-60.

Zemrak WR, Kenna GA. Association of antipsychotic and antidepressant drugs with Q-T interval prolongation. Am J Health Syst Pharm. 2008;65(11):1029-38.

Davila I, Sastre J, Bartra J, del Cuvillo A, Jauregui I, Montoro J, et al. Effect of H1 antihistamines upon the cardiovascular system. J Investig Allergol Clin Immunol. 2006;16(S-1):13-23.

Simko J, Lorincz I. The cardiotoxicity of macrolides: the role of interactions. In: A. Mendez-Vilas. Microbial pathogens and strategies for combating them: science, technology and education. 2013;3:1941-9.

Rubinsteina E, Camm J. Cardiotoxicity of fluoroquinolones. J Antimicrob Chemother. 2002;49(4):593-6.

Dumaine R, Roy ML, Brown AM. Blockade of HERG and Kv1.5 by ketoconazole. J Pharmacol Exp Ther. 1998;286:727-35.

Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira IN, Peter T. QT prolongation and torsades de pointes after administration of trimethoprim– sulfamethoxazole. Am J Cardiol. 1987;59:376-7.

Monlun E, Pillet O, Cochard JF, FavarelGarrigues JC, le Bras M. Prolonged QT interval with halofantrine. Lancet. 1993;341:1541-2.

Otsuka M, Kanamori H, Sasaki S. Torsades de pointes complicating pentamidine therapy of Pneumocystis carinii pneumonia in acute myelogenous leukemia. Intern Med. 1997;36:705-8.

Carlsson L, Amos GJ, Andersson B, Drews L, Duker G, Wadstedt G. Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: implications for proarrhythmic potential? J Pharmacol Exp Ther. 1997;282:220-7.

Hodak SP, Moubarak JB, Rodriguez I, Gelfand MC, Alijani MR, Tracy CM. QT prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report. Transplantation. 1998;66:535-7.

Kleinsasser A, Kuenszberg E, Loeckinger A. Sevoflurane, but not propofol, significantly prolongs the Q-T interval. Anesth Analg. 2000;90:25-7.

Horn JR. Important drug interactions and their mechanisms. In: Bertram G. Katzung, Susan B. Masters, Anthony J Trevor. Basic and Clinical Pharmacology. 12th edition, McGraw-Hill; 2012:1149-1162.

Banai S, Tzivoni D. Drug therapy for torsade de pointes. Journal of Cardiovascular Electrophysiology. 1993;4(2):206-10.

Tzivoni D, Banai S, Schuger C, Benhorin J, Keren A, Gottlieb S, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation. 1988;77:392-7.

Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. American Journal of Medicine. 2002;112(1):58-66.

Viskin S. Cardiac pacing in the long QT syndrome: review of available data and practical recommendations. Journal of Cardiovascular Electrophysiology. 2000;11(5):593-600.