Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Acquired long QT syndrome

Charles I Berul, MD
Peter J Zimetbaum, MD
Section Editors
John K Triedman, MD
Samuel Lévy, MD
Samuel Asirvatham, MD
Deputy Editor
Brian C Downey, MD, FACC


The long QT syndrome (LQTS) is a disorder of myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram (ECG) (waveform 1) [1-3]. This syndrome is associated with an increased risk of a characteristic life-threatening cardiac arrhythmia, known as torsades de pointes (TdP) (waveform 2A-B) [4,5]. The primary symptoms in patients with LQTS include palpitations, syncope, seizures, and sudden cardiac death (SCD).

The long QT syndrome may be either genetic or acquired [6-9]. Acquired LQTS usually results from drug therapy, hypokalemia, or hypomagnesemia (table 1). As will be described below, hypokalemia, hypomagnesemia, and bradycardia can increase the risk of drug-induced LQTS. In addition, some patients with acquired LQTS have an underlying "forme fruste" of congenital LQTS. (See 'Mutations in LQTS genes' below.)

The pathophysiology, causes, and management of acquired LQTS will be reviewed here. The clinical manifestations of acquired LQTS are similar to those in congenital disease and are discussed elsewhere. (See "Clinical features of congenital long QT syndrome".)


The normal range for the rate-corrected QT interval is similar in males and females from birth until late adolescence (0.37 to 0.44 sec). In adults, females have slightly longer QT intervals than males. A corrected QT interval of more than 0.45 sec is considered prolonged in men; the normal range generally is extended to 0.45 to 0.47 seconds in women (table 2) [10]. (See 'Diagnosis' below.)


Torsades de pointes (TdP) is a form of polymorphic ventricular tachycardia (VT) that occurs in the setting of acquired or congenital QT interval prolongation [4,5]. Polymorphic VT is defined as a ventricular rhythm faster than 100 beats per min with frequent variations of the QRS axis, morphology, or both [5,6]. In the specific case of TdP, these variations take the form of a progressive, sinusoidal, cyclic alteration of the QRS axis (waveform 2A-B). The peaks of the QRS complexes appear to "twist" around the isoelectric line of the recording; hence the name torsades de pointes or "twisting of the points".

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Oct 16, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Moss AJ. Long QT Syndrome. JAMA 2003; 289:2041.
  2. Li H, Fuentes-Garcia J, Towbin JA. Current concepts in long QT syndrome. Pediatr Cardiol 2000; 21:542.
  3. Jackman WM, Friday KJ, Anderson JL, et al. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988; 31:115.
  4. El-Sherif N, Turitto G. Torsade de pointes. Curr Opin Cardiol 2003; 18:6.
  5. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am 2001; 85:321.
  6. Khan IA. Long QT syndrome: diagnosis and management. Am Heart J 2002; 143:7.
  7. Wehrens XH, Vos MA, Doevendans PA, Wellens HJ. Novel insights in the congenital long QT syndrome. Ann Intern Med 2002; 137:981.
  8. Camm AJ, Janse MJ, Roden DM, et al. Congenital and acquired long QT syndrome. Eur Heart J 2000; 21:1232.
  9. Haverkamp W, Breithardt G, Camm AJ, et al. The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J 2000; 21:1216.
  10. Moss AJ. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol 1993; 72:23B.
  11. Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990; 81:686.
  12. Roden DM. Taking the "idio" out of "idiosyncratic": predicting torsades de pointes. Pacing Clin Electrophysiol 1998; 21:1029.
  13. Kupershmidt S, Yang IC, Hayashi K, et al. The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines. FASEB J 2003; 17:2263.
  14. Yang T, Roden DM. Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence. Circulation 1996; 93:407.
  15. Ridley JM, Milnes JT, Benest AV, et al. Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamide. Biochem Biophys Res Commun 2003; 306:388.
  16. Jurkiewicz NK, Sanguinetti MC. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circ Res 1993; 72:75.
  17. Yang T, Snyders DJ, Roden DM. Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects. Circulation 1995; 91:1799.
  18. Numaguchi H, Mullins FM, Johnson JP Jr, et al. Probing the interaction between inactivation gating and Dd-sotalol block of HERG. Circ Res 2000; 87:1012.
  19. Kamiya K, Nishiyama A, Yasui K, et al. Short- and long-term effects of amiodarone on the two components of cardiac delayed rectifier K(+) current. Circulation 2001; 103:1317.
  20. Daleau P, Lessard E, Groleau MF, Turgeon J. Erythromycin blocks the rapid component of the delayed rectifier potassium current and lengthens repolarization of guinea pig ventricular myocytes. Circulation 1995; 91:3010.
  21. Volberg WA, Koci BJ, Su W, et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J Pharmacol Exp Ther 2002; 302:320.
  22. Roy M, Dumaine R, Brown AM. HERG, a primary human ventricular target of the nonsedating antihistamine terfenadine. Circulation 1996; 94:817.
  23. Suessbrich H, Waldegger S, Lang F, Busch AE. Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole. FEBS Lett 1996; 385:77.
  24. Drolet B, Khalifa M, Daleau P, et al. Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval. Circulation 1998; 97:204.
  25. Dumaine R, Roy ML, Brown AM. Blockade of HERG and Kv1.5 by ketoconazole. J Pharmacol Exp Ther 1998; 286:727.
  26. Kang J, Wang L, Chen XL, et al. Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Mol Pharmacol 2001; 59:122.
  27. Anson BD, Weaver JG, Ackerman MJ, et al. Blockade of HERG channels by HIV protease inhibitors. Lancet 2005; 365:682.
  28. Schram G, Zhang L, Derakhchan K, et al. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol 2004; 142:1300.
  29. Katchman AN, McGroary KA, Kilborn MJ, et al. Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther 2002; 303:688.
  30. Katchman AN, Koerner J, Tosaka T, et al. Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther 2006; 316:1098.
  31. Suessbrich H, Schönherr R, Heinemann SH, et al. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes. Br J Pharmacol 1997; 120:968.
  32. Viskin S, Alla SR, Barron HV, et al. Mode of onset of torsade de pointes in congenital long QT syndrome. J Am Coll Cardiol 1996; 28:1262.
  33. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003; 89:1363.
  34. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350:1013.
  35. Yang P, Kanki H, Drolet B, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002; 105:1943.
  36. De Ponti F, Poluzzi E, Cavalli A, et al. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview. Drug Saf 2002; 25:263.
  37. Viskin S, Justo D, Halkin A, Zeltser D. Long QT syndrome caused by noncardiac drugs. Prog Cardiovasc Dis 2003; 45:415.
  38. Straus SM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med 2004; 164:1293.
  39. Magnano AR, Talathoti NB, Hallur R, et al. Effect of acute cocaine administration on the QTc interval of habitual users. Am J Cardiol 2006; 97:1244.
  40. De Bruin ML, Pettersson M, Meyboom RH, et al. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 2005; 26:590.
  41. Straus SM, Sturkenboom MC, Bleumink GS, et al. Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death. Eur Heart J 2005; 26:2007.
  42. Roden DM, Woosley RL, Primm RK. Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care. Am Heart J 1986; 111:1088.
  43. Maisel WH, Kuntz KM, Reimold SC, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med 1997; 127:281.
  44. Coplen SE, Antman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation 1990; 82:1106.
  45. Meltzer RS, Robert EW, McMorrow M, Martin RP. Atypical ventricular tachycardia as a manifestation of disopyramide toxicity. Am J Cardiol 1978; 42:1049.
  46. Strasberg B, Sclarovsky S, Erdberg A, et al. Procainamide-induced polymorphous ventricular tachycardia. Am J Cardiol 1981; 47:1309.
  47. Olshansky B, Martins J, Hunt S. N-acetyl procainamide causing torsades de pointes. Am J Cardiol 1982; 50:1439.
  48. Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol 1990; 65:74A.
  49. Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94:2535.
  50. Wang T, Bergstrand RH, Thompson KA, et al. Concentration-dependent pharmacologic properties of sotalol. Am J Cardiol 1986; 57:1160.
  51. Køber L, Bloch Thomsen PE, Møller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet 2000; 356:2052.
  52. Torp-Pedersen C, Møller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341:857.
  53. Ellenbogen KA, Stambler BS, Wood MA, et al. Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. J Am Coll Cardiol 1996; 28:130.
  54. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613.
  55. Brown MA, Smith WM, Lubbe WF, Norris RM. Amiodarone-induced torsades de pointes. Eur Heart J 1986; 7:234.
  56. Hohnloser SH, Klingenheben T, Singh BN. Amiodarone-associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia. Ann Intern Med 1994; 121:529.
  57. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997; 30:791.
  58. Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs 2002; 62:1649.
  59. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009; 360:225.
  60. Hill SL, Evangelista JK, Pizzi AM, et al. Proarrhythmia associated with cisapride in children. Pediatrics 1998; 101:1053.
  61. Ray WA, Murray KT, Meredith S, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 2004; 351:1089.
  62. Barbey JT, Pezzullo JC, Soignet SL. Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol 2003; 21:3609.
  63. Ohnishi K, Yoshida H, Shigeno K, et al. Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Ann Intern Med 2000; 133:881.
  64. Unnikrishnan D, Dutcher JP, Varshneya N, et al. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood 2001; 97:1514.
  65. Drolet B, Simard C, Roden DM. Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currents. Circulation 2004; 109:26.
  66. Singer JW. Cardiac toxicity of arsenic trioxide. Blood 2001; 98:1633; author reply 1633.
  67. Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation 2010; 121:1047.
  68. Hennessy S, Bilker WB, Knauss JS, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 2002; 325:1070.
  69. Stöllberger C, Huber JO, Finsterer J. Antipsychotic drugs and QT prolongation. Int Clin Psychopharmacol 2005; 20:243.
  70. Herings RM, Stricker BH, Leufkens HG, et al. Public health problems and the rapid estimation of the size of the population at risk. Torsades de pointes and the use of terfenadine and astemizole in The Netherlands. Pharm World Sci 1993; 15:212.
  71. Zitron E, Scholz E, Owen RW, et al. QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids. Circulation 2005; 111:835.
  72. Choy AM, Darbar D, Dell'Orto S, Roden DM. Exaggerated QT prolongation after cardioversion of atrial fibrillation. J Am Coll Cardiol 1999; 34:396.
  73. Makkar RR, Fromm BS, Steinman RT, et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993; 270:2590.
  74. Zeltser D, Justo D, Halkin A, et al. Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors. Medicine (Baltimore) 2003; 82:282.
  75. Drici MD, Clément N. Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf 2001; 24:575.
  76. Drici MD, Knollmann BC, Wang WX, Woosley RL. Cardiac actions of erythromycin: influence of female sex. JAMA 1998; 280:1774.
  77. Locati EH, Zareba W, Moss AJ, et al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation 1998; 97:2237.
  78. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999; 99:529.
  79. Bradley TJ, Metzger DL, Sanatani S. Long on QT and low on calcium. Cardiol Young 2004; 14:667.
  80. Eryol NK, Colak R, Ozdoğru I, et al. Effects of calcium treatment on QT interval and QT dispersion in hypocalcemia. Am J Cardiol 2003; 91:750.
  81. Benoit SR, Mendelsohn AB, Nourjah P, et al. Risk factors for prolonged QTc among US adults: Third National Health and Nutrition Examination Survey. Eur J Cardiovasc Prev Rehabil 2005; 12:363.
  82. Curry P, Fitchett D, Stubbs W, Krikler D. Ventricular arrhythmias and hypokalaemia. Lancet 1976; 2:231.
  83. Kay GN, Plumb VJ, Arciniegas JG, et al. Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients. J Am Coll Cardiol 1983; 2:806.
  84. McKibbin JK, Pocock WA, Barlow JB, et al. Sotalol, hypokalaemia, syncope, and torsade de pointes. Br Heart J 1984; 51:157.
  85. Wolfe CL, Nibley C, Bhandari A, et al. Polymorphous ventricular tachycardia associated with acute myocardial infarction. Circulation 1991; 84:1543.
  86. Kenigsberg DN, Khanal S, Kowalski M, Krishnan SC. Prolongation of the QTc interval is seen uniformly during early transmural ischemia. J Am Coll Cardiol 2007; 49:1299.
  87. Halkin A, Roth A, Lurie I, et al. Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome. J Am Coll Cardiol 2001; 38:1168.
  88. Kurita T, Ohe T, Marui N, et al. Bradycardia-induced abnormal QT prolongation in patients with complete atrioventricular block with torsades de pointes. Am J Cardiol 1992; 69:628.
  89. Furushima H, Niwano S, Chinushi M, et al. Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans. Heart 1998; 79:56.
  90. Goldstein DS. The electrocardiogram in stroke: relationship to pathophysiological type and comparison with prior tracings. Stroke 1979; 10:253.
  91. Di Pasquale G, Pinelli G, Andreoli A, et al. Torsade de pointes and ventricular flutter-fibrillation following spontaneous cerebral subarachnoid hemorrhage. Int J Cardiol 1988; 18:163.
  92. Drew BJ, Califf RM, Funk M, et al. Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses. Circulation 2004; 110:2721.
  93. Al-Khatib SM, LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval. JAMA 2003; 289:2120.
  94. Haugaa KH, Bos JM, Tarrell RF, et al. Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clin Proc 2013; 88:315.
  95. European Heart Rhythm Association, Heart Rhythm Society, Zipes DP, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247.
  96. Tzivoni D, Banai S, Schuger C, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation 1988; 77:392.
  97. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S729.
  98. DiSegni E, Klein HO, David D, et al. Overdrive pacing in quinidine syncope and other long QT-interval syndromes. Arch Intern Med 1980; 140:1036.
  99. Tötterman KJ, Turto H, Pellinen T. Overdrive pacing as treatment of sotalol-induced ventricular tachyarrhythmias (torsade de pointes). Acta Med Scand Suppl 1982; 668:28.
  100. Keren A, Tzivoni D, Gavish D, et al. Etiology, warning signs and therapy of torsade de pointes. A study of 10 patients. Circulation 1981; 64:1167.
  101. Assimes TL, Malcolm I. Torsade de pointes with sotalol overdose treated successfully with lidocaine. Can J Cardiol 1998; 14:753.
  102. Takahashi N, Ito M, Inoue T, et al. Torsades de pointes associated with acquired long QT syndrome: observation of 7 cases. J Cardiol 1993; 23:99.
  103. Raehl CL, Patel AK, LeRoy M. Drug-induced torsade de pointes. Clin Pharm 1985; 4:675.
  104. Vukmir RB, Stein KL. Torsades de pointes therapy with phenytoin. Ann Emerg Med 1991; 20:198.
  105. WASSERMAN F, BRODSKY L, KATHE JH, et al. The effect of molar sodium lactate in quinidine intoxication. Am J Cardiol 1959; 3:294.
  106. Choy AM, Lang CC, Chomsky DM, et al. Normalization of acquired QT prolongation in humans by intravenous potassium. Circulation 1997; 96:2149.
  107. Cooke RA, Chambers JB, Singh R, et al. QT interval in anorexia nervosa. Br Heart J 1994; 72:69.
  108. Mont L, Castro J, Herreros B, et al. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry 2003; 42:808.