Dennis S. Miura

Atrial contraction is an important determinant of pulmonary venous flow.

Pulmonary venous flow has two phases (systolic and diastolic) in normal subjects when studied by pulsed Doppler echocardiography. Only one phase of pulmonary venous flow (diastolic) was observed in six patients without synchronous atrial contraction (four patients with atrial fibrillation and two with complete atrioventricular [AV] block). This pattern reversed to normal (biphasic) when AV synchrony was reestablished by cardioversion to sinus rhythm in patients with atrial fibrillation and by AV sequential pacing in patients with complete AV block. Thus, both atrial and ventricular contraction and relaxation are important determinants of pulmonary venous flow.

QT prolongation and the antiarrhythmic efficacy of amiodarone

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

The Cimetidine-Lidocaine Interaction

Lidocaine is a widely used antiarrhythmic agent whose plasma clearance varies with changes in hepatic blood flow. Cimetidine, an H2-receptor antagonist, has been shown to decrease hepatic blood flow. To ascertain whether cimetidine affected serum lidocaine concentration, we studied 21 patients receiving lidocaine infusions and divided them into two groups. Fifteen patients received cimetidine, 300 mg every 6 hours, in addition to lidocaine; six patients received only lidocaine. In 14 of the 15 patients receiving both lidocaine and cimetidine, a rise in serum lidocaine levels was seen, whereas no change was noted in the control group. Six of the 15 patients were found to have levels in the toxic range and two had symptoms. An additional three patients on lidocaine received diphenhydramine, an H1-receptor antagonist. No elevation in serum lidocaine levels was noted after administration of diphenhydramine. We conclude that there exists an interaction between lidocaine and cimetidine and that the rise in serum lidocaine levels may be mediated by cimetidines inhibition of the H2 receptor.

Prolongation of QT interval and antiarrhythmic action of bepridil

Studies were undertaken with bepridil, a new calcium blocker that prolongs the QT interval, to determine the antiarrhythmic and possible arrhythmogenic properties of this agent. The technique of programmed electrical stimulation was employed to evaluate bepridil in 15 patients with symptomatic ventricular tachycardia (VT). Bepridil prevented VT induction in 7 of 15 patients. Bepridil prolonged the QT and refractoriness and a linear correlation could be demonstrated between the percent change in QTc and refractory period prolongation for the bepridil-protected group. Bepridil in one patient reduced by one the number of stimuli required to induce VT, but no spontaneous arrhythmias were noted. Bepridil thus possesses antiarrhythmic properties with a minimal proarrhythmic effect.

Antiarrhythmic effects of cibenzoline

Thirty-three patients with ventricular tachyarrhythmias were referred for evaluation of their arrhythmias using programmed electrical stimulation to guide antiarrhythmic therapy. Cibenzoline succinate, a new antiarrhythmic agent, was compared to procainamide in patients with ventricular tachycardia. Cibenzoline was given intravenously, initially 1.0 mg/kg, then in 1 mg/kg increments to a maximum of 3.0 mg/kg, during electrophysiologic testing. The results were compared to procainamide, which was also administered intravenously to 1000 and then to 1500 mg. Cibenzoline provided protection against ventricular tachycardia induction in 16 of 33 patients. The PR interval increased 13%, QRS duration widened 26%, and QTc interval was prolonged by 7%. There was a 9% fall in mean arterial blood pressure. Procainamide prevented ventricular tachycardia induction in 21 out of 31 patients tested. The PR interval increased 11%, QRS duration widened 27%, and QTc interval prolonged by 8%. Cibenzoline was given orally to 13 patients for chronic treatment. Chronic oral cibenzoline therapy after a mean follow-up of 8.8 months caused a reduction of ventricular ectopy from 666 to 190 beats/hr. Ventricular tachycardia events decreased per Holter monitor recording from 6 to 0.6. Cibenzoline therapy was discontinued in 5 of 13 patients due to break-through arrhythmias (nonsustained ventricular tachycardia on Holter monitor and recurrence of symptoms). Cibenzoline may be an effective antiarrhythmic agent in selected patients.

Evaluation of lorcainide in patients with symptomatic ventricular tachycardia

One hundred patients with inducible ventricular tachycardia (VT) on electrophysiologic studies underwent serial drug testing with procainamide, lidocaine and lorcainide to determine comparative efficacy. Acute intravenous administration was followed by repeat programmed electrical stimulation (PES) studies on separate days for each antiarrhythmic agent. Lorcainide prevented VT induction in 69% of the 100 patients studied, procainamide in 50% of the 75 patients studied and lidocaine in 30% of 53 patients. After PES and serial drug testing, 46 patients were started on lorcainide, 9 on procainamide and 45 on other antiarrhythmic drug regimens. Eighty percent of the patients have remained on lorcainide therapy, whereas 47% have continued on other drug therapies started over 17.5-month mean follow-up period. Despite sleep-wake disturbances and a need for sedation at night, lorcainide therapy was well tolerated in this population and remained an effective antiarrhythmic agent with prolonged administration.

Antiarrhythmic efficacy of ethmozine in patients with ventricular tachycardia as determined by programmed electrical stimulation.

The antiarrhythmic properties of ethmozine were studied in 27 patients with a history of a cardiac arrest or symptomatic ventricular tachycardia. Programmed electrical stimulation studies were performed in 20 men and seven women with a mean age of 62 years and a mean left ventricular ejection fraction of 43%. All patients had inducible ventricular tachycardia by programmed electrical stimulation while off all antiarrhythmic therapy. Patients were then tested on procainamide if their treatment with this drug orally had not previously failed. Procainamide, 1000 and 1500 mg, was administered intravenously, and ventricular tachycardia could be provoked in 14 of 18 patients. Ethmozine was given in an oral loading regimen starting 24 to 36 hours later. After 500 mg oral ethmozine, patients were given 15 mg/kg ethmozine every 8 hours for seven to nine doses prior to drug testing. Ethmozine did not significantly change the baseline heart rate, blood pressure, and QTc interval from the initial drug-free values. The PR and QRS intervals were significantly prolonged. Seven patients were protected on oral ethmozine; 14 patients still had ventricular tachycardia inducible at programmed electrical stimulation testing, and six patients developed ventricular tachycardia spontaneously on ethmozine and were not tested in the programmed electrical stimulation laboratory. One patient had gastrointestinal complaints and was not discharged on the drug. The five patients who tolerated the oral protocol without side effects and who were protected against programmed stimulation induction of ventricular tachycardia were discharged on oral therapy. One patient on long-term therapy appeared to develop an allergic reaction to the agent with unexplained fevers and was switched to amiodarone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pacing termination of ventricular tachycardia: Influence of antiarrhythmic-slowed ectopic rate

The success of pacing stimuli interruption of ventricular tachycardia (VT) was examined in 77 episodes of sustained VT induced in 31 patients undergoing programmed electrical stimulation studies. Once VT was induced, a trial to terminate the arrhythmia by means of the technique of entrainment was attempted. If this failed, rapid burst pacing faster than the VT was begun to try and terminate the tachycardia. In 30 patients off antiarrhythmic agents, entrainment was effective in terminating VT in 27%, while burst pacing was also effective in 27%. In 37% of patients, VT was accelerated or ventricular fibrillation was produced by pacing techniques, and these patients required defibrillation. Following antiarrhythmic therapy that failed to prevent VT induction but did result in slowing of VT rate, entrainment was only successful in 23% of trials, while burst pacing was successful in 34% of trials. The incidence of acceleration of VT on therapy was 32%. There was no appreciable difference in acceleration noted with or without antiarrhythmic therapy. Regardless of therapy, the slower the VT rate, the greater success of pacing termination of VT and the lower the incidence of VT acceleration. Antiarrhythmic agents that significantly slow the VT rate increase the success rate of pacing stimuli interruption of VT and decrease the incidence of VT acceleration and thus the need for defibrillation. The results suggest that antiarrhythmic agents that slow the VT rate may increase the effectiveness of antiarrhythmic pacemakers in terminating VT.

Antiarrhythmic drug efficacy at electrophysiology testing: Predictive effectiveness of procainamide and flecainide

In an effort to assess the ability of procainamide to predict effectiveness of antiarrhythmic agents at programmed electrical stimulation (PES) testing, we compared the result of procainamide at PES testing with that of all of the other agents studied. One hundred fifty-three patients underwent PES studies because of either sustained or nonsustained ventricular tachycardia (VT). Procainamide prevented VT induction in 79 of 153 patients. Seventy-four of the remaining 153 were inducible for VT on procainamide, with 55 of these being protected by another antiarrhythmic agent (p less than 0.001). If procainamide failed to prevent VT induction, other conventional and experimental agents were equally as likely to be effective in preventing VT induction. Analysis of flecainide acetate as a predictor of efficacy was also evaluated. Fifty-five patients received flecainide and 29 of these were protected at PES testing; 26 of these patients were also protected with another agent. When VT was inducible in patients who received flecainide, 15 of these 26 patients were protected by another agent, either conventional or experimental (p less than 0.01). Thus, if procainamide or flecainide prevented VT induction they accurately predicted effectiveness of other drugs; however, when they did not prevent VT induction, they served as a poor predictor of the possible effectiveness of other drugs. Serial drug testing at PES studies with multiple conventional and experimental drugs increases the likelihood of finding an effective antiarrhythmic agent.

Intravenous quinidine by intermittent bolus for electrophysiologic studies in patients with ventricular tachycardia

The safety and efficacy of intravenous quinidine gluconate, using intermittent boluses of 80 mg/cc every 5 minutes to a total dose of 800 mg, was evaluated in 61 patients referred for electrophysiologic studies (EPS). Patients were referred because of out-of-hospital cardiac arrest (12), symptomatic ventricular tachycardia (VT) (24), asymptomatic VT (18), syncope of unknown origin (6), and supraventricular arrhythmias (1). Clinical heart failure was present in 74% of patients, with a mean ejection fraction of 45 +/- 3 for all patients. Quinidine prevented VT induction in 78% of patients at a mean dose of 9.6 mg/kg and facilitated VT induction in 7% of patients. Quinidine failed to decrease mean arterial pressure in 14 patients, and in the remaining 47 patients arterial pressure decreased by 16%. Six patients had hemodynamically significant hypotension. Two patients had hypotension severe enough to require saline administration, while four had hypotension not needing fluid replacement. Sixteen percent of patients experienced other side effects. Quinidine can be administered safely by intermittent infusion and is effective in preventing programmed stimulation induction of VT. Carefully monitored, intravenous intermittent bolus administration of quinidine should be utilized more frequently in EPS, since significant adverse side effects are infrequent.