Purpose: To review the pharmacology, electrophysiology, and toxicity of amiodarone and to discuss the clinical results produced when amiodarone is used as therapy for patients with atrial fibrillat...

Amiodarone: Reevaluation of an Old Drug

To evaluate the effect of beta adrenergic stimulation on the duration of the anterograde refractory period of the accessory pathway, isoproterenol was infused in seven patients with the Wolff-Parkinson-White syndrome. In two patients the effect of isoproterenol was studied during long-term oral amiodarone administration. To avoid rate-related changes induced by isoproterenol, the anterograde refractory period of the accessory pathway was determined using the single test stimulus method at identical basic cycle lengths. Isoproterenol shortened the anterograde refractory period of the accessory pathway in six of the seven patients studied. In two of the three patients with an initial anterograde refractory period of the accessory pathway of equal to or less than 290 ms, shortening measured 30 ms. In three patients having an anterograde refractory period of the accessory pathway of more than 290 ms, isoproterenol abbreviated these values by 30, 60 and 80 ms, respectively. The greatest amount of shortening was observed in patients having the longest initial values for the anterograde refractory period of their accessory pathway. In the two patients receiving oral amiodarone therapy, isoproterenol shortened the anterograde refractory period of the accessory pathway by 180 and 60 ms, respectively, indicating that the effect of isoproterenol can not be prevented by long-term oral amiodarone administration. Our observations may be of importance in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation. They suggest that beta adrenergic stimulation induced by hypotension or anxiety may result in shortening of the anterograde refractory period of the accessory pathway, leading to increased ventricular rates during atrial fibrillation.

Effect of isoproterenol on the anterograde refractory period of the accessory pathway in patients with the Wolff-Parkinson-White syndrome.

Ten patients with an unusual form of ventricular tachycardia (VT) are described. All were young (mean age 21 years) at the onset of VT, symptoms were of long duration (mean 7 years), none had symptomatic organic heart disease, VT was induced by atrial and ventricular stimulation, VT had a characteristic QRS morphologic picture resembling right bundle branch block with left-axis deviation and 9 had early retrograde His deflections during VT. Supraventricular tachycardia (SVT) was excluded in every patient by electrophysiologic study, although QRS morphologic characteristics and clinical stability of these patients during tachycardia frequently led to the diagnosis of SVT before referral. Four patients received verapamil during electrophysiologic testing. Verapamil slowed and terminated VT in all. Three patients are being treated chronically with oral verapamil, 3 patients with conventional antiarrhythmic agents and 1 with a radiofrequency ventricular pacemaker.

Ventricular tachycardia induced by atrial stimulation in patients without symptomatic cardiac disease

Ajmaline given intravenously produced complete anterograde block in the accessory pathway of 32 of 59 patients with the Wolff-Parkinson-White syndrome. An electrophysiologic investigation performed 1 day later revealed that failure of ajmaline to produce complete anterograde block in the accessory pathway corresponded to a short refractory period of this pathway (less than 270 ms). The use of ajmaline intravenously is advanced as a reliable and rapid procedure for identifying those patients with the Wolff-Parkinson-White syndrome who have a short refractory period of the accessory pathway and are possibly at risk of circulatory insufficiency or sudden death if atrial fibrillation supervenes.

Use of ajmaline in patients with the Wolff-Parkinson-White syndrome to disclose short refractory period of the accessory pathway

Recurrent sustained ventricular tachycardia (VT) with QRS morphology of the right bundle branch block and left axis deviation was studied in 4 patients without any underlying heart diseases. The mean VT rate was 155 beats/min and the endocardial catheter mapping during VT showed the earliest activation site at the left ventricular lateral wall near the apex. In all patients, rapid pacing from the right ventricular outflow tract during VT resulted in constant fusion beats except for the last entrained beat (thus VT was entrained), while pacing from the right ventricular apex and from the earliest activation site failed to demonstrate entrainment. During entrainment from the right ventricular outflow tract (mean pacing rate 168 beats/min), conduction intervals from the pacing site to the earliest activation site (St-A interval) and to the right ventricular apex (St-B interval) were measured in 3 patients. The St-A intervals were 400, 410 and 440 ms and the St-B intervals were 80, 70 and 90 ms, respectively. A small dose of verapamil (1.0 mg) was administered during VT, which resulted in a decrease of VT rate by a mean of 23 beats/min. During entrainment from the right ventricular outflow tract the St-A interval was prolonged in all 3 patients while the St-B interval remained the same. In conclusion, the mechanism of this VT was best explained by reentry with an area of slow conduction. Verapamil slowed the rate of VT by prolonging conduction within the area of slow conduction. Tachycardia entrainment makes possible a selective examination of antiarrhythmic drug effect on the area of slow conduction within the reentry circuit of VT.

Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for reentry with an area of slow conduction and effect of verapamil.

The effect of procainamide, quinidine, ajmaline and amiodarone on the effective refractory period of the accessory pathway in the (A-V) anterograde and retrograde directions was studied in relation to the length of this period before drug administration. All patients had the Wolff-Parkinson-White syndrome and were studied with intracavitary recordings and programmed electrical stimulation of the heart using identical basic cycle lengths and test stimulus intervals before and after drug administration. The patients were separated into two groups, those in whom the effective refractory period of the accessory pathway was 270 ms or greater (Group 1) and those in whom it was less than 270 (Group 2). In the anterograde direction the magnitude of increase in the length of the effective refractory period of the accessory pathway after drug administration was related to its initial length. Only modest lengthening of this period could be accomplished in patients with an initially short period. In evaluating the effect of drugs in patients with the Wolff-Parkinson-White syndrome, the role of the initial length of the effective refractory period of the accessory pathway should be considered.

Effect of drugs in the wolff-parkinson-white syndrome: Importance of initial length of effective refractory period of the accessory pathway

In 7 of 43 patients in whom a sustained ventricular tachycardia could be induced during programmed electrical stimulation by a single ventricular premature stimulus, an identical tachycardia could also be initiated by a single atrial premature stimulus. This phenomenon was observed only in those patients in whom the ventricular tachycardia could be induced by a single ventricular extrastimulus having a prematurity index (ratio between the longest ventricular premature stimulus interval resulting in tachycardia and the duration of the basic cycle length of the paced ventricular rhythm) above 54 percent. No single instance of initiation of ventricular tachycardia by atrial premature stimuli was observed in patients with a ventricular prematurity index below 54 percent or requiring more than one consecutive ventricular extrastimulus to have tachycardia initiated. Other features of patients showing initiation of ventricular tachycardia by atrial premature stimuli were a right bundle branch block configuration of the QRS complex during tachycardia in all seven patients and a relatively slow rate during tachycardia. In one patient ventricular tachycardia was terminated by a conducted atrial premature stimulus.

Initiation and termination of ventricular tachycardia by supraventricular stimuli. Incidence and electrophysiologic determinants as observed during programmed stimulation of the heart.

Clinical incidence of tachycardia and ease of initiation during programmed electrical stimulation of the heart

In 7 of 43 patients in whom a ~ustaincd ventricular tachycardia could he induced eluring programmed electrical stimulation hy a single ventricular premature stimulus, an identical tachycardia could also be initiated by a single atrial premature stimulus. This phenomenon was observed only in those patients in whom the ventricular tachycardia could bc induced by a single ventricular extraslimulus having a prematurity index (ratio between the longest ventricular premature stimulus interval resulting in tachycardia and the duration of the basic cycle length of the paced ventricular rhythm) ahove 54(X. No single instance of initiation of ventricular tachycardia by atrial premature stimuli was observed in patients with a ventricular prematurity index below 54% or requiring morc than one consecutive ventricular cxtrastimulus to have tachycardia initiated. Other I'eatures or patients showing initiation or ventricular tachycardia by atrial premature stimuli were a right bundle branch block conhguratiDn or the QRS complex during tachycardia in all seven patients and a relatively slo\v rate during tachycardia. In one patient ventricular tachycardia Vv'£lS terminated hy a conducted atrial premature stimulus. instances of ventricular tachycardia initiated by a su­ praventricular stimulus have been reported in human beings (1-8J. However, no study has been reported of the incidence of this phenomenon or of its electro­ physiologic determinants in a large series of patients with ventricular tachycardia. In this article these as­ pects are analyzed and their possible therapeutic im­ plications discussed in a series of 54 patients with clinically documented recurrent episodes of sustained ventricular tachycardia in whom an identical arrhyth­ mia was induced during a stimulation study.

Incidence and Electrophysiologic Determinants as Observed During Programmed Stimulation of the Heart

Mechanisms of termination of aberrant conduction due to retrograde concealed penetration of the bundle branches during circusmovement tachycardia utilizing an accessory pathway

Edgard J. Vanagt

Papers

Effect of drugs in the wolff-parkinson-white syndrome: Importance of initial length of effective refractory period of the accessory pathway

Initiation and termination of ventricular tachycardia by supraventricular stimuli. Incidence and electrophysiologic determinants as observed during programmed stimulation of the heart.

Clinical incidence of tachycardia and ease of initiation during programmed electrical stimulation of the heart

Incidence and Electrophysiologic Determinants as Observed During Programmed Stimulation of the Heart

Mechanisms of termination of aberrant conduction due to retrograde concealed penetration of the bundle branches during circusmovement tachycardia utilizing an accessory pathway