Raúl J. Levi

Clinical efficacy of amiodarone as an antiarrhythmic agent.

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 to 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Intraventricular trifascicular blocks. Review of the literature and classification

Abstract The right bundle branch and the two divisions—anterior and posterior—of the left constitute the three main terminal fascicles of the intraventricular conduction system. Depending on whether conduction is permanently or only intermittently interrupted in these three fascicles, eight different possibilities or combinations of intraventricular and atrioventricular conduction disturbances may occur. A theoretical design covering all those possibilities is suggested, and clinical examples are bestowed for each of them. The existence of these syndromes, which we have termed altogether “trifascicular blocks”, provides one of the most valuable evidences of the anatomical and functional “trilaterality” of the human intraventricular conduction system.

Intraventricular trifascicular blocks. The syndrome of right bundle branch block with intermittent left anterior and posterior hemiblock

Abstract When conduction is interrupted in the right bundle branch and only intermittently in the two divisions, anterior and posterior, of the left, a very peculiar and as yet undescribed electrocardiographic syndrome occurs. Its main feature is the presence of two different right bundle branch block patterns, with completely opposite directions of the ÂQRS (superiorly and to the left in one; inferiorly and to the right, in the other); together with severe A-V conduction disturbances. Four cases of this singular syndrome are here described and analyzed. Such cases can be considered exceptional experiments of nature, providing most invaluable evidence for the existence of block within the anterior and posterior divisions of the left bundle branch. However, the syndrome of “right bundle branch block with intermittent left anterior and posterior hemiblock” is only one of the several possibilities of what we have named “intraventricular trifascicular blocks,” which will be considered in the second part of this paper.

Five cases of intermittent left anterior hemiblock

Abstract The first 5 cases of intermittent left anterior hemiblock (block in the anterior division of the left bundle branch) are reported. These cases can be considered exceptional experiments of nature, providing both invaluable evidence for the existence of left anterior hemiblock and useful material for studying, with great accuracy, the changes that this conduction disturbance produces on the previously normal or abnormal electrocardiogram in man. The three major electrocardiographic features of left anterior hemiblock are found to be: (1) An ÂQRS directed at approximately −60 °; (2) the presence of a Q 1 S 3 pattern, simulating a counterclockwise rotation of the heart; and (3) a QRS widening of not greater than 0.02 sec.

Wenckebach Periods in the Bundle Branches

Two cases of intermittent bundle-branch block in which Wenckebach periods could be directly visualized are reported. The conduction ratios were either 3:2 or 4:3, as are commonly seen in cases of the Wenckebach phenomenon of atrioventricular (A-V) conduction. Other groups of beats apparently showing 3:1 and 4:1 bundle-branch block were interpreted as indicating incompletely concealed Wenckebach periods in the bundle branches, with actual conduction ratios of 3:2 and 4:3, respectively.Three prerequisites are necessary for the occurrence of either direct or incompletely concealed Wenckebach periods in the bundle branches: (1) The opening beat should be normally conducted (in the affected bundle branch); (2) the second beat should be conducted with a delay of no more than 0.04 to 0.06 sec; (3) the damaged bundle branch should not be activated retrogradely in the closure beat.Wenckebach periods in the bundle branches may be completely concealed if the conduction delay lasts more than 0.04 to 0.06 sec in the opening beat. In cases of bilateral bundle-branch block, Wenckebach periods in the bundle branches may be indirectly visualized through changes in the A-V conduction.

Wenckebach Periods of Alternate Beats Clinical and Experimental Observations

Wenckebach periods of alternate beats (AW) can be described as a 2:1 atrioventricular (A-V) block in which the conducted P waves show progressive prolongation of the P-R interval of the Wenckebach type. However, while classical Wenckebach periods terminate with a single blocked P wave, AW necessarily ends with (or begins from) two consecutive blocked P waves. Five clinical cases and several experimental examples of AW are reported. Recovery curves of A-V conduction were constructed, and it was demonstrated that AW is related to a marked prolongation of both the absolute and relative refractory periods. All the cases were associated with intraventricular block. In addition, recording of His bundle potentials in one case, histological study of the conduction system in another, and the experimental observations, support the view that AW tends to occur below the A-V node, in one of the main ventricular conducting fascicles. Four of the five patients developed complete heart block and Adams-Stokes seizures.

Relationships Between Increased Automaticity and Depressed Conduction in the Main Intraventricular Conducting Fascicles of the Human and Canine Heart

Escapes from the injured fascicle (EIF) were investigated in 281 cases of bundle branch block (BBB), and during 35 experiments in which rate-dependent BBB was provoked in the intact canine heart. During vagal stimulation, EIF occurred in 27 of the 35 canine experiments, in seven of 24 patients with phase 4 (bradycardia-dependent) BBB, and in nine of 31 patients with fixed BBB. Changes in the degree of fascicular injury and phase 4 BBB were accompanied by correlative changes in the frequency and coupling interval of the EIF, indicating the existence of a close relationship between degree of injury, phase 4 BBB and EIF or enhanced automaticity within the affected fascicle. Therapeutic doses of isoproterenol and lidocaine were tested and were shown to have a simultaneous and sometimes concordant effect on the BBB and the EIF. Occasionally in the acute experiments on dogs, commonly in chronic patients, or at times in patients under the effects of lidocaine, a dissociation or desynchronization between the phase 4 BBB and the EIF was documented. This dissociation implies the existence of other physiologic factors, which may eventually cause the occurrence of concealed or abortive escapes. The fact that phase 3 (tachycardia dependent) and phase 4 BBB can be identified in patients or provoked experimentally in the intact canine heart, with or without EIF, provides with a model of great potential value for studying effects of antiarrhythmic drugs.

Experimental Production of Rate-Dependent Bundle Branch Block in the Canine Heart

The main ventricular conducting fascicles were slightly injured in anesthetized dogs by gently scratching them with a blunt needle introduced through the ventricular wall. Initially the bundle branch block that resulted was rate independent (stage 1). When conduction returned to normal, both premature atrial and vagal stimulation reproduced the bundle branch block (stage 2). During stage 2 (5–15 minutes), three conduction ranges were documented: an early (phase 3) block range, a late (phase 4) block range, and an intermediate normal conduction range. The normal conduction range was narrow at the beginning but widened progressively, mostly at the expense of the phase 4 block range. Another period during which only phase 4 bundle branch block occurred (stage 3) preceded total normalization (stage 4). The escape beats that arose from the injured fascicle were most abundant and had the shortest coupling during stage 1, they were less common and their coupling became longer during stages 2 and 3, and they disappeared in stage 4. The tachycardia-dependent or phase 3 bundle branch block was related to a prolongation of refractoriness; the bradycardia-dependent or phase 4 bundle branch block was attributed to slight hypopolarization, enhanced spontaneous diastolic depolarization, and a shift in the threshold potential toward zero. These abnormalities were assumed to be secondary to the hypopolarization, which was probably the basic derangement. This hypothesis satisfactorily accounts for the observation that phase 3 and phase 4 bundle branch block commonly coexist in the same injured fascicle.

A Reappraisal of Supernormal Conduction

According to some authors [1] “supernormal conduction is said to occur when impulse conduction is better than expected”. According to others [2] “conduction may be called supernormal when it is better than anticipated under the circumstances, or where propagation succeeds early in diastole and fails at all other times”. Still others [3] are of opinion that “the term supernormal phase designates a short, early, and limited period of the cardiac cycle during which a stimulus elicits either a totally unexpected response or one that is less abnormal than expected considering the state of recovery from the preceding impulse”.

The Experimental Evidence for the Role of Phase 3 and Phase 4 Block in the Genesis of A-V Conduction Disturbances

Clinical (237, 692, 694) and experimental (240, 241) studies have demonstrated two types of rate dependent conduction disturbances. In one of these, the conduction disturbance occurs when the heart rate is accelerated (phase 3 block) and in the other, the conduction disturbance appears after long diastolic intervals or when the heart rate is slowed (phase 4 block). The term ‘phase 3 block’ has been used since it is assumed that the blocked impulse reaches the injured fibers of the involved region during phase 3 of abnormally prolonged action potentials (237, 240, 692, 694). Phase 4 block has been attributed to a loss of maximum diastolic potential (hypopolarization), enhanced spontaneous diastolic depolarization (SDD), and a shift in threshold potential towards zero (692, 694, 760).