Drug-induced arrhythmias and sudden cardiac death: implications for the pharmaceutical industry

Drug Discovery Today

Volumn 14, Issue 11-12, 2009, Pages 589-597

  Killeen, Matthew J ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (6 METHYL 2 PYRIDYL)ETHYL] 4 (4 METHYLSULFONYLAMINOBENZOYL)PIPERIDINE; CLARITHROMYCIN; DISOPYRAMIDE; DOFETILIDE; KETOCONAZOLE; POTASSIUM CHANNEL; POTASSIUM CHANNEL HERG; TERFENADINE;

ARRHYTHMOGENESIS; CARDIOTOXICITY; DRUG DETERMINATION; DRUG INDUSTRY; DRUG MARKETING; DRUG SAFETY; DRUG SCREENING; HEART ARRHYTHMIA; HUMAN; NONHUMAN; QT PROLONGATION; REVIEW; SIDE EFFECT; SUDDEN DEATH; TORSADE DES POINTES;

ANIMALS; ARRHYTHMIAS, CARDIAC; CARDIOVASCULAR AGENTS; DEATH, SUDDEN, CARDIAC; DRUG INDUSTRY; HUMANS; LONG QT SYNDROME; POTASSIUM CHANNEL BLOCKERS;

EID: 67349175359     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2009.03.004     Document Type: Review

References (72)

1. Nerbonne J.M., and Kass R.S. Physiology and molecular biology of ion channels contributing to ventricular repolarization. In: Gussak I., and Antzelevitch C. (Eds). Cardiac Repolarization Bridging Basic and Clinical Science (2003), Humana Press Inc. 25-62
2. + current is composed of two currents in guinea pig atrial cells. Am. J. Physiol. 260 2 Pt 2 (1991) H393-399
3. Roden D.M. Drug-induced prolongation of the QT interval. N. Engl. J. Med. 350 (2004) 1013-1022
4. Roden D.M. Taking the "idio" out of "idiosyncratic": predicting torsades de pointes. Pacing Clin. Electrophysiol. 21 (1998) 1029-1034
5. Aiba T., et al. Cellular and ionic mechanism for drug-induced long QT syndrome and effectiveness of verapamil. J. Am. Coll. Cardiol. 45 (2005) 300-307
6. Romano C., et al. Rare cardiac arrhythmias of the pediatric age. I. Repetitive paroxysmal tachycardia. Minerva Pediatr. 15 (1963) 1155-1164
7. Jervell A., and Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am. Heart J. 54 (1957) 59-68
8. Roden D.M. Clinical practice Long-QT syndrome. N. Engl. J. Med. 358 (2008) 169-176
9. Curran M.E., et al. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80 (1995) 795-803
10. Splawski I., et al. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat. Genet. 17 (1997) 338-340
11. Splawski I., et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 102 (2000) 1178-1185
12. Selzer A., and Wray H.W. Quinidine syncope. Paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrhythmias. Circulation 30 (1964) 17-26
13. Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch. Mal. Coeur. Vaiss. 59 (1966) 263-272
14. Fermini B., and Fossa A.A. The impact of drug-induced QT interval prolongation on drug discovery and development. Nat. Rev. Drug Discov. 2 (2003) 439-447
15. Pratt C.M., et al. Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: distinguishing a drug effect from spontaneous variability. Am. Heart J. 131 (1996) 472-480
16. Monahan B.P., et al. Torsades de pointes occurring in association with terfenadine use. JAMA 264 (1990) 2788-2790
17. Barbey J.T., et al. Spontaneous adverse event reports of serious ventricular arrhythmias, QT prolongation, syncope, and sudden death in patients treated with cisapride. J. Cardiovasc. Pharmacol. Ther. 7 (2002) 65-76
18. Ray W.A., et al. Oral erythromycin and the risk of sudden death from cardiac causes. N. Engl. J. Med. 351 (2004) 1089-1096
19. Varriale P. Fluoxetine (Prozac) as a cause of QT prolongation. Arch. Intern. Med. 161 (2001) 612
20. Honig P.K., et al. Terfenadine-ketoconazole interaction pharmacokinetic and electrocardiographic consequences. JAMA 269 (1993) 1513-1518
21. Hayashi Y., et al. Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia. Pacing Clin. Electrophysiol. 22 (1999) 672-674
22. Follmer C.H., and Colatsky T.J. Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes. Circulation 82 (1990) 289-293
23. + channel structure-activity relationships and mechanisms of drug-induced QT prolongation. Annu. Rev. Pharmacol. Toxicol. 43 (2003) 441-461
24. Mounsey J.P., and DiMarco J.P. Cardiovascular drugs, Dofetilide. Circulation 102 (2000) 2665-2670
25. Mitcheson J.S., et al. Trapping of a methanesulfonanilide by closure of the HERG potassium channel activation gate. J. Gen. Physiol. 115 (2000) 229-240
26. + channels: friend and foe. Trends Pharmacol. Sci. 22 (2001) 240-246
27. Tamargo J., et al. Pharmacology of cardiac potassium channels. Cardiovasc. Res. 62 (2004) 9-33
28. Antzelevitch C., et al. Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ. Res. 69 (1991) 1427-1449
29. Killeen M.J., et al. Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart. Acta Physiol. (Oxf.) 189 (2007) 33-46
30. Baker L.C., et al. Enhanced dispersion of repolarization and refractoriness in transgenic mouse hearts promotes reentrant ventricular tachycardia. Circ. Res. 86 (2000) 396-407
31. London B., et al. Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT. J. Physiol. 578 (2007) 115-129
32. Antzelevitch C., et al. Transmural dispersion of repolarization and arrhythmogenicity: the Brugada syndrome versus the long QT syndrome. J. Electrocardiol. 32 (1999) 158-165
33. Antzelevitch C., et al. Cellular and ionic mechanisms underlying erythromycin-induced long QT intervals and torsade de pointes. J. Am. Coll. Cardiol. 28 (1996) 1836-1848
34. Antzelevitch C., et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J. Cardiovasc. Electrophysiol. 10 (1999) 1124-1152
35. Antzelevitch C. Cellular basis and mechanism underlying normal and abnormal myocardial repolarization and arrhythmogenesis. Ann. Med. 36 (2004) 5-14
36. Liu D.W., and Antzelevitch C. Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. Circ. Res. 76 (1995) 351-365
37. Zygmunt A.C., et al. Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle. Am. J. Physiol. Heart Circ. Physiol. 281 (2001) H689-697
38. Akar F.G., et al. Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome. Circulation 105 (2002) 1247-1253
39. Killeen M.J., et al. Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis. Acta Physiol. (Oxf.) 191 (2007) 43-58
40. Fabritz L., et al. Prolonged action potential durations, increased dispersion of repolarization, and polymorphic ventricular tachycardia in a mouse model of proarrhythmia. Basic Res. Cardiol. 98 (2003) 25-32
41. Roden D.M., and Hoffman B.F. Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length. Circ. Res. 56 (1985) 857-867
42. Di Diego J.M., et al. Cisapride-induced transmural dispersion of repolarization and torsade de pointes in the canine left ventricular wedge preparation during epicardial stimulation. Circulation 108 (2003) 1027-1033
43. 2+ channel agonist Bay K 8644. Circ. Res. 62 (1988) 563-571
44. 2+ current. Circ. Res. 64 (1989) 977-990
45. Ben Caref E., et al. Role of subendocardial Purkinje network in triggering torsade de pointes arrhythmia in experimental long QT syndrome. Europace 10 (2008) 1218-1223
46. Sicouri S., and Antzelevitch C. Afterdepolarizations and triggered activity develop in a select population of cells (M cells) in canine ventricular myocardium: the effects of acetylstrophanthidin and Bay K 8644. Pacing Clin. Electrophysiol. 14 11 Pt 2 (1991) 1714-1720
47. Burashnikov A., and Antzelevitch C. Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations. J. Cardiovasc. Electrophysiol. 13 (2002) 172-177
48. Bass A.S., et al. International Life Sciences Institute (Health and Environmental Sciences Institute HESI) initiative on moving towards better predictors of drug-induced torsades de pointes. Br. J. Pharmacol. 154 (2008) 1491-1501
49. Eckardt L., et al. Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin. J. Cardiovasc. Pharmacol. 32 (1998) 425-434
50. Thomsen M.B., et al. Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation. Cardiovasc. Res. 73 (2007) 521-530
51. Hondeghem L.M., et al. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation 103 (2001) 2004-2013
52. Hondeghem L.M., et al. Phase 2 prolongation, in the absence of instability and triangulation, antagonizes class III proarrhythmia. Cardiovasc. Res. 50 (2001) 345-353
53. Shah R.R., and Hondeghem L.M. Refining detection of drug-induced proarrhythmia: QT interval and TRIaD. Heart Rhythm 2 (2005) 758-772
54. Clancy C.E., et al. Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation. Am. J. Physiol. Heart Circ. Physiol. 292 (2007) H66-75
55. + channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br. J. Pharmacol. 149 (2006) 481-489
56. Nuyens D., et al. Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat. Med. 7 (2001) 1021-1027
57. Head C.E., et al. Paced electrogram fractionation analysis of arrhythmogenic tendency in DeltaKPQ Scn5a mice. J. Cardiovasc. Electrophysiol. 16 (2005) 1329-1340
58. + current through a nifedipine inhibited inward channel. J. Pharmacol. Exp. Ther. 286 (1998) 9-22
59. Huelsing D.J., et al. Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes. Am. J. Physiol. Heart Circ. Physiol. 279 (2000) H250-259
60. Guerard N.C., et al. Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. J. Pharmacol. Toxicol. Methods 58 (2008) 32-40
61. +-ATPase is required for sensory system development in zebrafish. Development 135 (2008) 3425-3434
62. Heuser A., et al. Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am. J. Hum. Genet. 79 (2006) 1081-1088
63. Milan D.J., et al. Notch1b and neuregulin are required for specification of central cardiac conduction tissue. Development 133 (2006) 1125-1132
64. Chi N.C., et al. Genetic and physiologic dissection of the vertebrate cardiac conduction system. PLoS Biol. 6 (2008) e109
65. Arnaout R., et al. Zebrafish model for human long QT syndrome. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 11316-11321
66. Baker K., et al. Defective "pacemaker" current (Ih) in a zebrafish mutant with a slow heart rate. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 4554-4559
67. Milan D.J., et al. Drugs that induce repolarization abnormalities cause bradycardia in zebrafish. Circulation 107 (2003) 1355-1358
68. Lewin M.B., et al. Cisapride-induced long QT interval. J. Pediatr. 128 (1996) 279-281
69. Corey D.R., and Abrams J.M. Morpholino antisense oligonucleotides: tools for investigating vertebrate development. Genome Biol. 2 (2001) REVIEWS1015
70. Roden D.M. Repolarization reserve: a moving target. Circulation 118 (2008) 981-982
71. Bryant S., et al. A novel analysis method for characterising in vitro cardioactive drug effects. J. Pharmacol. Toxicol. Methods 58 (2008) 149
72. Reppel M., et al. The electrocardiogram of human embryonic stem cell-derived cardiomyocytes. J. Electrocardiol. 38 (2005) 166-170