Gregory K. Feld

Possible atrial proarrhythmic effects of class 1C antiarrhythmic drugs.

Abstract The class IC antiarrhythmic drugs encainide and flecainide have been used to treat ventricular arrhythmias. 1,2 Although not currently approved, they are also being used in the treatment of atria1 arrhythmias. 3,4 This antiarrhythmic action results from a marked depressant effect on conduction velocity and a moderate effect on prolonging refractoriness in the myocardium. 5,6 This marked depression of conduction velocity also results in the highest incidence of ventricular proarrhythmic effects observed with any class of antiarrhythmic drug. 7,8 However, less is known regarding their potential to produce atria1 proarrhythmic effects. 3,4 Recently we observed 6 patients who were being treated with flecainide or encainide for preexisting ventricular or atria1 arrhythmias, and who developed new or modified symptomatic atria1 arrhythmias with a rapid ventricular response. In 2 cases, life-threatening consequences arose from the arrhythmia. The clinical details of these cases are presented and the potential mechanisms of the atria1 proarrhythmic effects of the 1C drugs are discussed.

Comparative electrophysiologic profiles of calcium antagonists with particular reference to bepridil.

The calcium antagonist bepridil hydrochloride differs pharmacologically from the conventional agents that block the myocardial slow channel. Its clinical electrophysiologic effects are poorly defined. The effects of 2 mg/kg + 1 mg/kg of intravenously administered bepridil in 10 patients were compared with those of 3 mg/kg + 1 mg/kg in 9 patients undergoing electrophysiologic evaluation of clinical symptoms. The overall effects of the 2 regimens did not differ significantly. The drug reduced the heart rate slightly; it had no effect on the PR interval but significantly lengthened the AH interval by 2 to 10%, HV by 2 to 12% and QTc by 5 to 8%. The most striking effect was the prolongation of the functional (up to 17%, p less than 0.001) and the effective (up to 13%, p less than 0.001) refractory periods of the atrioventricular node with a lengthening of the Wenckebach cycle (up to 17%, p less than 0.001). In contrast to the action of verapamil, bepridil significantly prolonged the ventricular (4 to 7%, p less than 0.01 to p less than 0.001) and the atrial (12 to 19%, p less than 0.05 to p less than 0.001) effective refractory periods. The data indicate that bepridil hydrochloride has a wide spectrum of electrophysiologic activity in man consistent with inhibitory actions on myocardial slow and fast channels and a significant lengthening of cardiac repolarization. These overall effects suggest that the antiarrhythmic profile of the drug is likely to be wider than those of conventional calcium antagonists.

Macroreentrant ventricular tachycardia and coronary artery disease in cerebrotendinous xanthomatosis

Abstract Cerebrotendinous xanthomatosis, a metabolic lipid disorder characterized by a defect in the conversion of cholesterol into bile acids, is a rare disease with 1 The His-Purkinje system macroreentrant ventricular tachycardia (VT) is an uncommon arrhythmia, and accounts for the underlying mechanism in approximately 6% of induced sustained monomorphic VT. 2,3 We herein describe a patient with cerebrotendinous xanthomatosis, a history of sudden cardiac death and 2 morphologies of VT due to 2 different mechanisms.

A young woman with syncope and sudden death: What molecular mechanisms could be involved?

Patient K.D. first came to the electrophysiology service at the University of California, San Diego, in February 1991 with a complaint of a syncopal episode. This 20-year-old college student had been previously diagnosed with congenital long-QT syndrome, without associated deafness, at age 18 when she went there following multiple syncopal episodes. Both her mother and her sister had a prolonged QT interval on ECG, though neither of these relatives has had any documented symptoms or arrhythmias. Electrophysiologic evaluation of K.D. at her initial presentation revealed sustained, inducible, polymorphic ventricular tachycardia (PMVT) with double extra stimuli. Treatment was begun with P-blockade, phenytoin, and implantation of a VVI pacer with a programmed rate of 100. The patient had suffered two additional syncopal episodes following initiation of this therapy, prior to the present admission. Upon admission, the patient was noted on ECG to have an intermittently paced rhythm with frequent premature ventricular contractions and a markedly prolonged QT interval on native and paced beats (Figure 1). The evening of admission while on telemetry monitoring, she suffered a prolonged episode of torsades de pointes that resolved soon after cardiopulmonary resuscitation was begun and did not require defibrillation (Figure 2). The patient suffered multiple other selflimited episodes of PMVT, despite increased doses of P-blockers and continuation of phenytoin and pacing. Since she