Gerardo J. Nau

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.

Modulation of parasystolic activity by nonparasystolic beats.

We studied 12 patients with ventricular parasystole in whom pacemaker activity could be modulated by nonparasystolic beats (NPBs). In six patients (group 1) in whom the intrinsic parasystolic cycle length (XX interval) was obtained without interposed NPBs, we found that NPBs falling during the first half of the cycle prolonged the XRX interval (containing one NPB) and that NPBs falling during the second half of the cycle abbreviated the XRX interval; both effects were maximal when NPBs fell close to the middle of the cycle and were separated by a reversal point. However, because of mutual interference between parasystolic beats and NPBs, only 13.2–43.4% of the parasystolic cycle could be effectively scanned. We also found that the XRX and RX intervals were linearly related. This relationship served to establish that in six patients in whom the XX interval was not obtained (group 2), modulation showed a similar behavior, although neither the reversal point nor the sense of the modulation could be determined. In this report, we suggest diagnostic criteria of parasystolic modulation.

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.

Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Unmasking of ventricular preexcitation by vagal stimulation or isoproterenol administration.

Twenty-one patients were studied in whom ventricular preexcitation (VP) had been recorded in the past and had later disappeared, indicating antegrade block in the accessory pathway (AP), either spontaneously (10 patients) or under the effect of chronic treatment with amiodarone (11 patients). VP reappeared in nine cases during vagal stimulation, and in five cases during an i.v. isoproterenol infusion. Retrograde conduction over the AP was studied in four of the remaining seven patients and was found to be present in three and absent in one. Although these patients differ from the ordinary patient with concealed AP in that antegrade preexcitation had been demonstrated in the past, this study suggests that concealed VP may result from the following mechanisms: 1) an extremely prolonged refractory period in the AP, causing a ratedependent VP that can be identified during vagal stimulation; 2) a rate-independent depression of antegrade conduction that can be reversed by isoproterenol; 3) a depression of conduction that is apparently no longer reversible. Only in the latter case is a study of retrograde conduction needed to identify the concealed VP. These three mechanisms are likely to be a natural sequence of events leading to complete antegrade block in the AP.

Malignant Ventricular Arrhythmias in Chronic Chagasic Myocarditis

We studied 28 cases of chronic chagasic myocarditis (CCM) with frequent ventricular arrhythmias. Two‐hundred and three conventional ECGs recorded during 3 months showed ventricular extrasystoles (VE) ranging between 0.2 and 6 per ten beats in 100%; multiform VE in 97.04%; couplets in 79.31%; ventricular tachycardia (VT) in 42.85%; and R on T in 21.67%. A 24‐hour continuous recording showed that VE ranged between 3780 and 61733 (mean 16618 ± 2627); muitiform VE and couplets were present in 100% of patients, and VT was present in 78.5%. In 16 patients (group I) the frequency of VE was persistently high, without diurnal variation; 11 patients showed sustained reduction during sieeping hours and only one showed an increase during night sleep (group II). Even in group II, VE never disappeared for periods longer than 10 minutes. In five patients, four 24‐hour recordings were obtained at weekly intervals, and in five other patients a second 24‐hour recording was performed 10 to 24 months later. The remarkable frequency, persistence and low variability of ventricular arrhythmias in CCM suggest that such arrhythmias can be used as a most stable, reliable, but highly demanding model for testing the efficacy of antiarrhythmic drugs. (PACE, Vol. 5, March‐April, 1982)