Summary Verapamil is a novel antiarrhythmic agent which appears to act as a calcium-ion antagonist, blocking calcium transport across the myocardial cell membrane. It was given intravenously, in a dose of 10 mg, to thirty-two patients suffering from paroxysmal supraventricular tachycardia, and sinus rhythm was achieved promptly in all. Identical results were obtained in a further ten patients with supraventricular tachycardias associated with the Wolff-Parkinson-White or other pre-excitation syndromes. In a separate group of eighteen patients in whom A-V junctional tachycardias were induced during intracardiac electrography, conversion to sinus rhythm was achieved in fifteen patients, with prolongation of the cycle length in the others. Circus-movement tachycardias were induced in eight patients with the Wolff-Parkinson-White syndrome, and conversion to sinus rhythm was achieved in seven. The results were less consistent in patients with other supraventricular arrhythmias including ectopic atrial tachycardia and atrial flutter, and, in the single patient with supraventricular and ventricular tachycardia, only the former was controlled. In the single patient with atrial fibrillation complicating the Wolff-Parkinson-White syndrome who received verapamil, sinus rhythm was restored. Side effects were few and mild, with rare exceptions of profound hypotension, bradycardia and asystole; their management is discussed, and reasons are advanced why their occurrence is likely to be related either to the concomitant administration of beta-adrenergic blockers or to the presence of sinoatrial disease. It appears that verapamil is particularly suitable for the treatment of supraventricular tachycardias due to a circus movement as calcium antagonism is likely to be most effective in the N region of the atrioventricular node.

SUMMARY The electrophysiological effects of flecainide acetate (2 mg/kg as an intravenous infusion over five minutes) were assessed in 47 patients undergoing electrophysiological study. Seven patients had normal electrophysiology, 16 had a direct accessory atrioventricular pathway, 12 had dual atrioventricular nodal (AH) pathways, five had paroxysmal ventricular tachycardia, six had conduction system disease, and one patient had a left atrial tachycardia.No significant change occurred in sinus cycle length. The PA interval, AH interval, and HV interval were all significantly prolonged. The QRS complex duration increased significantly. The QT interval showed slight prolongation due entirely to the increase in QRS duration.Refractoriness of the atrial and ventricular myocardium was slightly prolonged, but was significant only at ventricular level. No significant change occurred in refractoriness of the norma atrioventricular node. Pronounced prolongation of retrograde "fast" AH pathway refractoriness was observed in those patients with dual AH pathways. Anterograde and retrograde accessory pathway refractoriness were both greatly increased.These electrophysiological properties strongly suggest that flecainide will be useful in the management of a wide variety of cardiac arrhythmias. It should be administered, however, with caution to patients with pre-existing conduction system disease. Because repolarisation is not delayed flecainide is unlikely to induce ventricular arrhythmias related to prolongation of the QT interval.Flecainide acetate4 (N-(2-piperidylmethyl)-2,5-bis (2,2,2-trifluoroethoxy) benzaamide acetate) belongs to a unique series of trifluoroethoxybenzamides' 2 which have proven antiarrhythmic activity against a variety of experimentally induced arrhythmias. [3][4][5] Human pharmacokinetic studies have shown that flecainide is almost completely absorbed after oral administration, undergoes minimal hepatic biotransformation, and has a long plasma elimination half-life ranging from 11 to 22 hours,67 properties that are highly desirable for the long term use of antiarrhythmic agents.This study was undertaken to investigate the acute electrophysiological effects of intravenous flecainide on cardiac conduction and refractoriness in man.

Changes in the QT and QTc intervals in 19 patients were studied at a ventricular paced rate difference of 50 beats/min. In all patients the measured QT interval shortened as the pacing rate was increased, from a mean value of 441 ms to 380 ms (p less than 0.001), but when corrected for heart rate the QTc lengthened from a mean value of 518 ms to 575 ms. In 11 patients the QT interval was measured at rest and immediately following exercise sufficient to increase the atrial rate by approximately 50 beats/min at identical ventricular paced rates. In all patients exercise-induced QT interval shortening from a mean value of 433 ms to 399 ms (p less than 0.001). These results show first that Bazett's formula is unsuitable for correction of QT interval induced by ventricular pacing, and second that heart rate and changes in sympathetic tone independently influence the duration of the QT interval. It is suggested that these results are relevant to the design of physiological pacemakers in which the duration of the QT interval influences the discharge frequency of the pacemaker and to the consideration of ventricular pacing for the treatment of abnormal repolarization syndromes.

SUMMARY Changes in the QT and QTc intervals were studied in 16 patients by atrial pacing at rates of 100, 130, and 150 beats/minute. In all patients the measured QT shortened when the atrial paced rate was increased, but when corrected for heart rate the QTc lengthened. Intravenously administered propranolol produced a bradycardia and a lengthening ofthe QT interval in 15 ofthe 16 patients studied. When the QT interval was corrected for heart rate using Bazett's formula the QTc was shortened in 13 patients, unchanged in one, and lengthened in two. However, when the QT interval was measured atidentical atrial paced rates the QT of the 15 patients studied was lengthened in 10 and unchanged in five. In none was the QT interval shortened. These results show firstly that Bazett's formula is unsuitable for correction of QT interval changes induced by atrial pacing, and secondly that, though intravenously administered propranolol usually produces a shortening of the QTc, when its effect is assessed directly by using an identical atrial paced rate the QT interval usually lengthens, or may remain unchanged, but never shortens. It is suggested that the formal assessment of drug induced QT interval changes should be made at identical atrial paced rates.Prolongation of the QT interval may occur after the administration of drugs such as quinidine,' amiodarone,2 disopyramide,3 the tricyclics,4 and the phenothiazines.5 The effect of propranolol on the QT interval remains controversial. Previous studies suggest that though it lengthens the measured QT, correction for heart rate by Bazett's hyperbolic correction factor" shows that the QTc is usually shortened.7 8 As such drugs may also cause changes in the heart rate, when assessing their effect on the QT interval the use of a correction factor for heart rate becomes necessary. Of the many formulae available Bazett's hyperbolic correction factor which corrects to a rate of 60 beats/min has been most readily accepted for use because it is simple to apply. In order to overcome the necessity for rate correction a new method has been devised for the assessment of drug induced QT changes using atrial pacing at identical rates before and after the administration of propranolol. This allows a direct comparison of these changes to be made and precludes the need for a correction factor. The purpose of this study was twofold. Firstly, to test the validity of Bazett's hyperbolic correction factor for QT changes induced by atrial pacing, and, secondly, to assess the

Using intracardiac recordings of electrical activity and programmed electrical stimulation of the heart, the effect of verapamil has been studied on the conduction times and refractory periods of the