Understanding drug-induced torsades de pointes: A genetic stance

Expert Opinion on Drug Safety

Volumn 7, Issue 3, 2008, Pages 231-239

  Kannankeril, Prince J ^a,b  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b MONROE CARELL JR CHILDREN S HOSPITAL AT VANDERBILT   (United States)

Author keywords

Adverse drug reaction; Long QT syndrome; Pharmacogenetics; Reduced repolarization reserve; Torsades de pointes

Indexed keywords

AMIODARONE; ANTIARRHYTHMIC AGENT; ANTIBIOTIC AGENT; ANTIPROTOZOAL AGENT; ARSENIC TRIOXIDE; CISAPRIDE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DOFETILIDE; ERYTHROMYCIN; FEXOFENADINE; FLUOXETINE; LEMAKALIM; NEUROLEPTIC AGENT; NORFLUOXETINE; PENTAMIDINE; PENTOBARBITAL; POTASSIUM CHANNEL; PROBUCOL; QUINIDINE; SOTALOL; TERFENADINE; THIORIDAZINE; VERAPAMIL;

DRUG BLOOD LEVEL; DRUG INDUCED DISEASE; DRUG MEGADOSE; DRUG METABOLISM; DRUG TOLERABILITY; ELECTROCARDIOGRAM; ENVIRONMENTAL FACTOR; GENE INTERACTION; GENETIC PREDISPOSITION; HEART PROARRHYTHMIA; HEART REPOLARIZATION; HEREDITY; HUMAN; HYPOKALEMIA; LONG QT SYNDROME; LOW DRUG DOSE; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PHARMACOLOGICAL BLOCKING; QT PROLONGATION; REVIEW; RISK FACTOR; TORSADE DES POINTES; CHEMICALLY INDUCED DISORDER; GENETICS; PHARMACOGENETICS;

ANTI-ARRHYTHMIA AGENTS; HUMANS; LONG QT SYNDROME; PHARMACOGENETICS; RISK FACTORS; TORSADES DE POINTES;

EID: 44949262972     PISSN: 14740338     EISSN: None     Source Type: Journal    
DOI: 10.1517/14740338.7.3.231     Document Type: Review

References (76)

1. Garrod AE. The debt of science to medicine: Harvein Oration of 1924, Royal College of Physicians. Oxford: Clarendon Press; 1924
2. Selzer A, Wray HW. Quinidine syncope: paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrythmias. Circulation 1964;30:17-26
3. Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss 1966;59:263-72
4. Romano C, Gemme G, Pongiglione R. Rare cardiac arrythmias of the pediatric age. II. Syncopal attacks due to paroxysmal ventricular fibrillation. (Presentation of 1st case in Italian pediatric literature). Clin Pediatr (Bologna) 1963;45:656-83
5. Ward OC. A new familial cardiac syndrome in children. J Ir Med Assoc 1964;54:103-6
6. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957;54:59-68
7. Brochier M, Fauchier JP. 'Torsades de pointe' and reentry induced by anti-arrhythmia agents. Arch Mal Coeur Vaiss 1978;71:477-88
8. Ching CK, Tan EC. Congenital long QT syndromes: clinical features, molecular genetics and genetic testing. Expert Rev Mol Diagn 2006;6:365-74
9. Plaster NM, Tawil R, Tristani-Firouzi M, et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 2001;105:511-9
10. Splawski I, Timothy YKW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004;119:19-31
11. Mohler PJ, Schott JJ, Gramolini AO, et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature 2003;421:634-9
12. Mohler PJ, Le Scouarnec S, Denjoy I, et al. Defining the cellular phenotype of 'ankyrin-B syndrome' variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation 2007;115:432-41
13. Wei J, Wang DW, Alings M, et al. Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation 1999;99:3165-71
14. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000;36:1-12
15. Furutani M, Trudeau MC, Hagiwara N, et al. Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel. Circulation 1999;99:2290-4
16. Roden DM, Viswanathan PC. Genetics of acquired long QT syndrome. J Clin Invest 2005;115:2025-32
17. Sanguinetti MC, Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature 2006;440:463-9
18. Fernandez D, Ghanta A, Kauffman GW, Sanguinetti MC. Physicochemical features of the HERG channel drug binding site. J Biol Chem 2004;279:10120-7
19. Ficker E, Kuryshev YA, Dennis AT, et al. Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol 2004;66:33-44
20. Cordes JS, Sun Z, Lloyd DB, et al. Pentamidine reduces hERG expression to prolong the QT interval. Br J Pharmacol 2005;145:15-23
21. Kuryshev YA, Ficker E, Wang L, et al. Pentamidine-induced long QT syndrome and block of hERG trafficking. J Pharmacol Exp Ther 2005;312:316-23
22. Guo J, Massaeli H, Li W, et al. Identification of IKr and its trafficking disruption induced by probucol in cultured neonatal rat cardiomyocytes. J Pharmacol Exp Ther 2007;321:911-20
23. Rajamani S, Eckhardt LL, Valdivia CR, et al. Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br J Pharmacol 2006;149:481-9
24. Anderson CL, Delisle BP, Anson BD, et al. Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation 2006;113:365-73
25. Rajamani S, Anderson CL, Anson BD, January CT. Pharmacological rescue of human K(+) channel long-QT2 mutations human ether-a-go-go-related gene rescue without block. Circulation 2002;105:2830-5
26. Liu K, Yang T, Viswanathan PC, Roden DM. New mechanism contributing to drug-induced arrhythmia: rescue of a misprocessed LQT3 mutant. Circulation 2005;112:3239-46
27. Kuryshev YA, Wang L, Wible BA, et al. Antimony-based antileishmanial compounds prolong the cardiac action potential by an increase in cardiac calcium currents. Mol Pharmacol 2006;69:1216-25
28. Yang T, Snyders D, Roden DM. Drug block of I(kr): model systems and relevance to human arrhythmias. J Cardiovasc Pharmacol 2001;38:737-44
29. Lazzara R. Amiodarone and torsade de pointes. Ann Intern Med 1989;111:549-51
30. Shimuzu W, McMahon B, Antzelevitch C. Sodium pentobarbital reduces transmural dispersion of repolarization and prevents torsades de pointes in models of acquired and congenital long QT syndrome. J Cardiovasc Electrophysiol 1999;10:154-64
31. Shah RR, Hondeghem LM. Refining detection of drug-induced proarrhythmia: QT interval and TRIaD. Heart Rhythm 2005;2:758-72
32. January CT, Riddle JM. Early afterdepolarizations: mechanism of induction and block A role for L-type Ca2+ current. Circ Res 1989;64:977-90
33. Zhang S, Zhou Z, Gong Q, et al. Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circ Res 1999;84:989-98
34. Shimuzu 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;26:1299-309
35. Aiba T, Shimizu W, Inagaki M, et al. Cellular and ionic mechanism for drug-induced long QT syndrome and effectiveness of verapamil. J Am Coll Cardiol 2005;45:300-7
36. Antzelevitch C. Role of transmural dispersion of repolarization in the genesis of drug-induced torsades de pointes. Heart Rhythm 2005;2:S9-15
37. Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long QT syndrome. Curr Opin Cardiol 2002;17:43-51
38. Sicouri S, Moro S, Litovsky S, et al. Chronic amiodarone reduces transmural dispersion of repolarization in the canine heart. J Cardiovasc Electrophysiol 1997;8:1269-79
39. Di Diego JM, Belardinelli L, Antzelevitch C. Cisapride-induced transmural dispersion of repolarization and torsade de pointes in the canine left ventricular wedge preparation during epicardial stimulation. Circulation 2003;108:1027-33
40. Xia Y, Liang Y, Kongstad O, et al. In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine. Heart Rhythm 2005;2:162-9
41. Yamaguchi M, Shimizu M, Ino H, et al. T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: a new index for arrhythmogenicity. Clin Sci (Lond) 2003;105:671-6
42. Houltz B, Darpo B, Edvardsson N, et al. Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study. Pacing Clin Electrophysiol 1998;21:1044-57
43. Grabowski M, Karpinski G, Filipiak KJ, Opolski G. Images in cardiovascular medicine. Drug-induced long-QT syndrome with macroscopic T-wave alternans. Circulation 2004;110:e459-60
44. Shimizu W, Antzelevitch C. Cellular and ionic basis for T-wave alternans under long-QT conditions. Circulation 1999;99:1499-507
45. Thomsen MB, Verduyn SC, Stengl M, et al. Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation 2004;110:2453-9
46. Thomsen MB, Volders PGA, Beekman JDM, et al. Beat-to-beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced torsades de pointes. J Am Coll Cardiol 2006;48:1268-76
47. Hondeghem LM, Carlsson L, Duker G. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation 2001;103:2004-13
48. Milberg P, Hilker E, Ramtin S, et al. Proarrhythmia as a class effect of quinolones: increased dispersion of repolarization and triangulation of action potential predict torsades de pointes. J Cardiovasc Electrophysiol 2007;18:647-54
49. 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;111:1088-93
50. Hondeghem LM. Relative contributions of TRIaD and QT to proarrhythmia. J Cardiovasc Electrophysiol 2007;18:655-7
51. 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;82:282-90
52. Makkar RR, Fromm BS, Steinman RT, et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993;270:2590-7
53. Zareba W, Moss AJ, Locati EH, et al. Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 2003;42:103-9
54. Rautaharju PM, Zhou SH, Wong S, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992;8:690-5
55. Arya A. Gender-related differences in ventricular repolarization: beyond gonadal steroids. J Cardiovasc Electrophysiol 2005;16:525-7
56. Yang T, Snyders DJ, Roden DM. Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res 1997;80:782-9
57. Numaguchi H, Johnson JP Jr, Petersen CI, Balser JR. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci 2000;3:429-30
58. Yang T, Roden DM. Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence. Circulation 1996;93:407-11
59. 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. J Am Coll Cardiol 2003;42:1777-82
60. Choy AM, Lang CC, Chomsky DM, et al. Normalization of acquired QT prolongation in humans by intravenous potassium. Circulation 1997;96:2149-54
61. 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;111:1088-93
62. 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;2:806-17
63. Choy AM, Darbar D, Dell'Orto S, Roden DM. Exaggerated QT prolongation after cardioversion of atrial fibrillation. J Am Coll Cardiol 1999;34:396-401
64. Darbar D, Hardin B, Harris P, Roden DM. A rate-independent method of assessing QT-RR slope following conversion of atrial fibrillation. J Cardiovasc Electrophysiol 2007;18:636-41
65. McCray R, Ritchie MD, Roden DM, Darbar D. Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndrome. Heart Rhythm 2006;3(Suppl 1):S114-5
66. Morissette P, Hreiche R, Turgeon J. Drug-induced long QT syndrome and torsade de pointes. Can J Cardiol 2005;21:857-864
67. Honig PK, Woosley RL, Zamani K, et al. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin. Clin Pharmacol Ther 1992;52:231-8
68. Ray WA, Murray KT, Meredith S, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 2004;351:1089-96
69. Kannankeril PJ, Roden DM, Norris KJ, et al. Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives. Heart Rhythm 2005;2:134-40
70. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999;99:529-33
71. 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;105:1943-8
72. Paulussen AD, Gilissen RA, Armstrong M, et al. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med 2004;82:182-8
73. Mank-Seymour AR, Richmond JL, Wood LS, et al. Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. Am Heart J 2006;152:1116-22
74. Arking DE, Pfeufer A, Post W, et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet 2006;38:644-51
75. Chang K, Barth AS, Kizana E, et al. CAPON, a nitric oxide synthase regulator associated with QT interval variation in humans, modulates cardiac repolarization in ventricular myocytes. Circulation 2006;114:II-167
76. Roden DM. Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med 2006;259:59-69