Ibutilide-Induced Long QT Syndrome and Torsade de Pointes Ramesh M. Gowda, 1 Gopikrishna Punukollu, 1 Ijaz A. Khan, 2 * Raghotham R. Patlola, 1 Furqan H. Tejani, 1 Braulio F. Cosme-Thormann, 1 Balendu C. Vasavada, 1 and Terrence J. Sacchi 1 Ibutilide is a class III antiarrhythmic agent used for the termination of atrial fibrillation and atrial flutter. It mainly affects membrane potassium currents and prolongs the cardiac action potential. This effect is reflected as QT interval prolongation on the surface electrocardiogram. Like other drugs that affect potassium currents, ibutilide is prone to induce a malignant ventricular tachycar- dia, torsade de pointes. We report four cases of torsade de pointes after administration of ibutilide for pharmacologic cardioversion of atrial fibrillation and atrial flutter; three of these cases required direct current cardioversion for termination of torsade de pointes. All four patients were female. We discuss the risk factors for development of ibutilide-induced torsade de pointes. Keywords: Ibutilide, torsade de pointes, ventricular tachycardia, long QT syndrome, atrial fibrilla- tion, atrial flutter, antiarrhythmic agents, potassium currents, pharmacologic cardioversion. INTRODUCTION The introduction of class III antiarrhythmic agents has enhanced the available drug treatment modalities for pharmacologic cardioversion of atrial fibrillation and atrial flutter, and an appreciation of the importance of the delayed rectifier potassium currents in the patho- genesis of various cardiac arrhythmias has led to the development of ibutilide, a class III antiarrhythmic agent. Ibutilide mainly affects rapidly activating de- layed rectifier potassium current I kr and prolongs the cardiac action potential. This effect is reflected as QT interval prolongation on the surface electrocardio- gram (ECG). Both preclinical and clinical studies have demonstrated the efficacy of ibutilide for the manage- ment of atrial fibrillation and atrial flutter. Published experience with ibutilide in randomized clinical trials reveals that conversion to sinus rhythm occurs in 31% of patients with atrial fibrillation and in 63% of those with atrial flutter. 1 Like other drugs that affect potas- sium currents and prolong QT interval, ibutilide is prone to induce a malignant ventricular tachycardia, torsade de pointes. 2 We present four cases of torsade de pointes after administration of ibutilide. CASE PRESENTATIONS Patient 1 A 54-year-old Hispanic woman presented with short- ness of breath for 3 days. She had a history of parox- ysmal atrial fibrillation and rheumatic heart disease with prior mitral valve replacement. Her medications included digoxin and warfarin. The ECG revealed atrial fibrillation with a ventricular rate of 140 beats per minute. A transthoracic echocardiogram revealed mildly suppressed left ventricular systolic function and a dilated left atrium. Serum chemistry and thy- roid-stimulating hormone levels were within normal limits. The INR was within therapeutic range. Ibuti- lide was used for pharmacologic cardioversion, and two doses of 1 mg were given 10 minutes apart over 10 minutes each. The corrected QT interval increased from 440 to 505 milliseconds after infusion of the dose of ibutilide. Immediately after the second dose, the patient developed an episode of torsade de pointes 1 Division of Cardiology, Long Island College Hospital, Brooklyn, NY; and 2 Division of Cardiology, Creighton University School of Medicine, Omaha, NE. *Address for correspondence: Creighton University Cardiac Cen- ter, 3006 Webster Street, Omaha, NE 68131. E-mail: ikhan@ cardiac.creighton.edu American Journal of Therapeutics 9, 527–529 (2002) 1075–2765 © 2002 Lippincott Williams & Wilkins, Inc.