Exercise Induced Fatal Sinusoidal Ventricular Tachycardia Secondary to Moricizine

Exercise Induced Fatal Sinusoidal Ventricular Tachycardia Secondary to Moricizine JOSE NAZARI, JERRY BAUMAN, THONG PHAM, LOU IVANOVICH, and RICHARD F. KEHOE From the Department of Medicine, Section of Cardiology, Illinois Masonic Medical Center and Departments of Medicine. Section of Cardiology, and Pharmacy Practice, University of Illinois. Chicago, Illinois

NAZARI, J., ET AL.: Exercise Induced Fatal Sinusoidal Ventricular Tachycardia Secondary to Moricizine. Moricizine has been touted as having a low incidence of proarrhythmic effects. We present a case of proarrhythmia from moricizine, which presented as exercise induced ventricular tachycardia, and review Ihe literature suggesting that this antiarrhythmic drug shares the proarrhythmic profile of other agents with predominant type Ic action. We concJude that moricizine has certain ciinical and electrophysioJogicoJ features that resemble type Ic antiarrhythmic agents. Precautions similar to those used when prescribing other drugs of this type should be followed when prescribing moricizine, including predischarge exercise testing. (PACE, Vol. 15, October, Part I 1992} proarrhythmic, moricizine, ventricular tachycardia

Introduction Moricizine has been generally believed to be an antiarrhythmic agent with a relatively low proarrhythmic potential' with only isolated case reports and a few studies reporting a significant incidence of proarrhythmia in patients with advanced structural heart disease. Recent evidence including the release of the results of the Cardiac Arrhythmia Suppression Trial [CAST II) late phase imply that these initial impressions may be incorrect. Moricizine has been variably classified as a Class la, Ib. or Ic antiarrhythmic agent during its investigation and subsequent approval by the Food and Drug Administration. Recently, Vaughan Williams,^ by reviewing all previously published data on the electrophysiology of moricizine, has concluded that this agent "possesses all the attributes of a class Ic agent". Herein we

Address for reprints: (ose Nazari, M.D.. Illinois Masonic Medical Center, 836 Wellington Avenue, Chicago, IL 60657. Fax: (312) 296-7024. Received January 23, 1992; revision April 14, 1992; accepted April 16, 1992.

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report a case of fatal ventricular tachycardia due to moricizine with morphological and clinical characteristics similar to those descrihed in arrhythmias secondary to flecainide.^"* Case Report A 64-year-old gentleman was admitted for initiation of antiarrhythmic therapy to avoid frequent discharges from his implanted defibrillator. He had suffered a myocardial infarction in the remote past, which left him with left ventricular dysfunction [ejection fraction of 15%). Three years prior to this admission he survived an out-of-hospital cardiac arrest and underwent electrophysiologically-guided therapy. Ventricular tachycardia was persistently inducible during a drug-free control study and after amiodarone therapy; therefore, implantation of an automatic defibrillator coupled with simultaneous coronary artery bypass grafting was chosen as treatment. Amiodarone was initially prescribed to suppress frequent episodes of nonsustained ventricular tachycardia and to prevent inappropriate defibrillation. The patient did well postoperatively and for the ensuing 6 months hut then developed symptoms of pulmonary toxic-

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ity from amiodarone. Despite discontinuation of amiodarone, the patient resumed his normal activities, which included an exercise program. An exercise stress test 1 year prior to admission revealed normal exercise capacity and no significant arrhythmias. Six months prior to admission, his original defibrillator was replaced by a second device (Cadence'^ Ventritex, Sunnyvale, CA, USA) because of battery depletion. Two months later he started receiving frequent shocks. By analysis of the stored electrograms of the device, these shocks appeared to represent appropriate defibrillator discharges for recurrent sustained ventricular tachycardia. Because of the discharge frequency and subsequent interference with his lifestyle, the patient was admitted to the hospital to initiate an antiarrhythmic agent that could decrease the frequency of his arrhythmias. Quinidine had been previously shown to be clinically ineffective and amiodarone was inadvisable because of the previous pulmonary toxicity. Flecainide was not chosen because of a perceived undue risk of proarrhythmia and the presence of underlying left ventricular dysfunction. Therefore, moricizine 200 mg three times daily was initiated. After 3 days of therapy, noninvasive programmed stimulation (by the defibrillator unit) was performed and ventricular tachycardia could not be induced. Ventricular fibrillation was induced to test for a potential increase in defibrillation threshold; the appropriate changes were made in the output of the unit (the defibrillation threshold was 15 joules and the output was programmed to 35 joules). Prior to planned discharge from the hospital, a routine exercise stress test was performed. Four minutes into a Bruce protocol, the patient suffered sustained ventricular tachycardia, which was appropriately recognized and terminated by the defibrillator device. Although the stress test was immediately discontinued, oxygen administered, and the patient allowed to rest, sustained ventricular tachycardia immediately recurred. This initial rhythm was relatively well tolerated but it could not be terminated by antitachycardia pacing or repeated high energy shocks from the internal defibrillator. Multiple external defibrillations were also administered resulting in restoration of sinus rhythm for only several beats; incessant ventricular tachycardia would always quickly recur. The

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tachycardia became sinusoidal in morphology within 2 minutes of its onset, resulting in immediate hemodynamic collapse (Fig. 1). Despite prolonged resuscitative efforts and drug therapy with epinephdne, sodium bicarbonate, hypertonic saline, lidocaine, and intravenous propranolol, an agonal ventricular rhythm ensued and the patient expired. An autopsy was refused by the family. Discussion The characteristics of proarrhythmia due to moricizine have been summarized in a report incorporating all the safety and efficacy trials of this drug in the United States. Of 908 patients (none with serious underlying arrhythmias or structural heart disease) administered moricizine, only 15 (1.7%) had serious proarrhythmia manifested as new sustained ventricular tachycardia (nine patients), torsade des pointes (one patient), new ventricular flutter or fibrillation (two patients), and syncope (one patient).' Two recent reports^'^ have investigated the antiarrhythmic and proarrhythmic effects of moricizine in patients with malignant or potentially malignant ventricular tachyarrhythmias in the presence of underlying structural heart disease of significance. Proarrhythmia, including new sustained and/or incessant ventricular tachycardia, was present in 19%-27% of patients. Tachyarrhythmias secondary to flecainide have been described as sinusoidal in morphology, frequently precipitated by exercise, and frequently incessant and unresponsive to prompt resuscitative measures."-^'^ The group from Northwestern has described the moricizine proarrhythmia as often having a sinusoidal morphology.^ To our knowledge, the case reported here represents only the second detailed description of the occurrence of sinusoidal ventricular tachycardia secondary to moricizine. It is likely that many such cases have occurred but gone undetected or unreported, particularly in view of the apparent late risk of proarrhythmia seen with type Ic agents. Our patient had been relatively stable and had responded well to defibrillation up to the time he received moricizine and an exercise test was performed. The temporal relationship between the onset of this fatal arrhythmia and moricizine treatment strongly suggests that this can indeed be attributed to moriciz-

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