Reduction Of Ventricular Premature Complexes Research Articles

Long-Term Effect of Continuing Sports Activity in Competitive Athletes With Frequent Ventricular Premature Complexes and Apparently Normal Heart

The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.

Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading.

To determine the time course of effects of amiodarone during an oral loading period. A prospective, nonrandomized study. Arrhythmia referral center at a university hospital. Fifty patients with refractory sustained ventricular tachycardia (n = 44) or ventricular fibrillation (n = 6) and frequent (greater than or equal to 30/h) ventricular premature complexes. Oral amiodarone, 1200 mg/d for 14 days and 400 mg/d thereafter. Ambulatory electrocardiographic monitorings, 12-lead electrocardiograms, and amiodarone blood levels on days 3, 5, 7, 9, 11, 13, and 28. Dramatic reductions of ventricular arrhythmias were noted during the first 72 hours of the therapy. Average ventricular premature complexes/h, couplets/h, and nonsustained ventricular tachycardias/24 h were 524 +/- 1224/h, 16 +/- 61/h, and 167 +/- 611/24 h, respectively, at baseline, and reduced to 140 +/- 243/h, 11 +/- 50/h, and 33 +/- 117/24 h, respectively, on day 3 (P less than 0.05 for all). Subsequent reductions of ventricular arrhythmias from day 3 to day 13 were more gradual but were still significant (P less than 0.05). A significant reduction of ventricular arrhythmias (greater than or equal to 70% reduction of ventricular premature complexes and greater than or equal to 90% reduction of nonsustained ventricular tachycardias) was noted in 50% of patients on day 3, in 65% on day 7, and in 83% on day 13. Prolongation of the QT interval exhibited a similar time course. There were no further differences in reduction of ventricular premature complexes or QT intervals between day 13 and day 28. Oral amiodarone given in loading doses produces rapid and dramatic reductions in spontaneous ventricular arrhythmias within 72 hours. Subsequent reductions of spontaneous arrhythmia were gradual and less dramatic.

Evaluation of disopyramide and mexiletine used alone and in combination for ventricular arrhythmias in patients with and without overt heart disease

The efficacies and side effects of disopyramide and mexiletine used alone and in combination were assessed in 29 patients with chronic ventricular arrhythmias. In combination therapy, one half or two thirds of the conventional doses of each drug were administered. Each patient underwent Holter electrocardiographic monitoring during 4 different periods: baseline, disopyramide alone, mexiletine alone and combination of the two drugs. The mean baseline number of ventricular premature complex per hour was 783 ± 521 (mean ± SD), which was significantly reduced with all three therapies. Disopyramide alone significantly reduced the ventricular premature complex frequency in patients with organic heart disease ( P < 0.05), but did not significantly reduce the ventricular premature complex frequency in patients with no apparent heart disease. In contrast, mexiletine alone significantly decreased the ventricular premature complex frequency in no apparent heart disease patients ( P < 0.05), but did not significantly reduce the ventricular premature complex frequency in organic heart disease patients. With disopyramide alone, patients having a significant reduction in ventricular premature complexes ( >= 83% reduction in ventricular premature complexes) or elimination of ventricular tachycardias tended to be more frequently found in organic heart disease than in no apparent heart disease. The opposite was observed with mexiletine alone. QTc interval with disopyramide alone was significantly prolonged, and the prematurity index of ventricular premature complexes was significantly lowered as compared to mexiletine alone or combination therapy ( P < 0.01 for disopyramide versus mexiletine; P < 0.05 for disopyramide versus combination therapy). During combination therapy, no patients withdrew from the study due to side effects. However, 3 patients receiving single drug therapy withdrew from the study due to severe side effects. Consequently, disopyramide is suggested to be more effective on ventricular premature complexes in organic heart disease than in no apparent heart disease patients, whereas the opposite was true for mexiletine. A combination of disopyramide and mexiletine in smaller doses may provide almost the same or enhanced antiarrhythmic effects, no aggravation of electrocardiographical parameters and less incidence of side effects when compared to the conventional dose of each drug alone.

Effectiveness of sotalol for therapy of complex ventricular arrhythmias and comparisons with placebo and class I antiarrhythmic drugs

In new antiarrhythmic drug development, key comparisons include those with placebo, standard (class I) agents and other β blockers. This review will cover the first 2 comparisons. The effectiveness of 2 doses of sotalol for complex ventricular arrhythmias has been compared with placebo in a 6-week, multicenter study (parallel, double-blind design) in 102 patients. The frequency of ventricular premature complexes (VPCs) was reduced only 10% with placebo, 75% with low-dose sotalol (160 mg administered twice daily) and 88% with high-dose sotalol (320 mg administered twice daily) (both p < 0.05 vs placebo). The defined efficacy criterion (≥75% VPC suppression) was achieved by 6% of patients taking placebo, 34% of patients taking low- and 71% of patients taking high-dose sotalol. Sotalol was generally well tolerated, especially with the lower dose. Heart rate decreased, and PR and QTc intervals increased modestly. An open, randomized, crossover study compared sotalol with procainamide in 33 patients. A reduction in VPCs of ≥75% was achieved in 22 patients (67%) with sotalol and in 13 patients (39%) with procainamide. Quinidine and sotalol have also been compared in a multicenter study in patients with chronic, complex VPCs, with results to be presented in the near future. Thus, sotalol's antiarrhythmic efficacy is well demonstrated by comparisons with placebo, and its effectiveness and tolerance are likely to compare favorably with standard class I drugs, suggesting its potential as a first-line antiarrhythmic agent.

Combination of disopyramide and mexiletine for better tolerance and additive effects for treatment of ventricular arrhythmias

The efficacy and tolerance of disopyramide and mexiletine used alone and in combination were studied in 21 patients with frequent (≥30/h) ventricular premature complexes. Ambulatory electrocardiographic monitoring was performed at baseline and during therapy with disopyramide alone, mexiletine alone and a combination of disopyramide and mexiletine. During single drug therapy, the dose of disopyramide was 602 +- 152 mg/day and that of mexiletine was 738 ± 144 mg/day. During combination therapy with smaller doses of disopyramide (524 ± 134 mg/day) and mexiletine (652 ± 146 mg/day), no patient had side effects. At baseline before therapy, the mean number of ventricular premature complexes per hour, was 608 ± 757, of couplets per hour was 22.4 ± 45.8 and of episodes of nonsustained ventricular tachycardia/24 h was 219.7 ± 758.2. The mean number of ventricular premature complexes per hour was reduced to 156 ± 217 with disopyramide alone, 188 ± 298 with mexiletine alone and 76 ± 144 with combination therapy (p < 0.05 for combination therapy versus disopyramide or mexiletine alone; p=NS for disopyramide versus mexiletine).Individually, an effective regimen (>;83% reduction in ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 5 (24%) of 21 patients during therapy with disopyramide alone, in 3 (14%) receiving mexiletine alone and in 13 (62%) receiving combination therapy (p < 0.05 for combination therapy versus disopyramide or mexiletine; p = NS for disopyramide versus mexiletine).Thus, the antiarrhythmic effects of disopyramide and mexiletine are additive. A combination of disopyramide and mexiletine in smaller and well tolerated doses may avoid dose-related side effects and is more effective than either drug used alone at higher doses. Therefore, when disopyramide or mexiletine is ineffective because dose-related side effects limit the maximal tolerated dose, combination therapy in smaller and more tolerable doses may avoid side effects and may be more effective than treatment with either drug alone at the maximal tolerated dose.

Comparison of twice daily with thrice daily administered encainide for benign or potentially lethal ventricular arrhythmias

The antiarrhythmic efficacy of encainide administered 2 (group A) or 3 times daily (group B) was evaluated in a randomized, placebo-controlled trial involving 101 patients with benign or potentially malignant ventricular arrhythmias. In group A, encainide was titrated at dosages of 35, 50 and 75 mg twice daily and in group B at dosages of 25, 35 and 50 mg 3 times daily. Drug efficacy, as judged by repeated ambulatory monitoring, was defined as >75% reduction in ventricular premature complexes combined with a >90% abolition of pairs and runs of nonsustained ventricular tachycardia. In group A, 27 of 52 patients (52%) had their arrhythmia suppressed by the drug compared with 34 of 49 (69%) in group B (difference not significant). There was a trend toward better arrhythmia control in group B if a total daily dose of >100 mg was necessary for arrhythmia suppression. Side effects were frequent in both groups (24 vs 28%, difference not significant). Thus, encainide administered twice daily effectively suppresses ventricular arrhythmias in this patient population.

The prognostic value of the changes in the mode of ventricular tachycardia induction noted during therapy with a marked reduction of ventricular ectopic activity

The prognostic significance of changes in the mode of induction of ventricular tachycardia (VT) noted during therapy was studied in 49 patients with sustained VT or ventricular fibrillation. Before treatment, all patients had inducible sustained VT by programmed stimulation (one to three extrastimuli) and frequent (≥30/hr) ventricular premature complexes (VPCs). On the discharge regimen, VT was no longer inducible by programmed stimulation in 22 patients (group 1). Twenty-seven patients (group 2) with persistent induction of VT despite extensive serial drug testings were discharged on a regimen that resulted in a marked reduction of VPCs on Holter monitoring (≥50% reduction of VPCs, ≥90% reduction of couplets, and abolition of nonsustained VT). The modes of induction at baseline and on the discharge regimen were compared in each patient in group 2. Induction of VT was more difficult, requiring more aggressive stimulation protocol in 5 of 27 patients, unchanged in 14 patients, and easier in 8 patients. The duration of follow-up was 20 ± 13 months (mean ± SD). Arrhythmia-free survival rates at 6, 12, 18, and 24 months were 95%, 89%, 82%, and 73% in group 1, 92%, 84%, 75%, and 75% in group 2, 93%, 83%, 77%, and 69% in 27 patients with noninducibility or harder induction, and 95%, 90%, 79%, and 79% in 22 patients with the same or easier induction, respectively. The differences were not significant. This nonrandomized study suggests that in selected patients with recurrent VT and frequent VPCs at baseline, changes in the mode of induction of VT (noninducible vs inducible; harder vs not harder) noted during therapy may not have prognostic significance if the therapy is accompanied by a marked reduction of VPCs. Randomized studies should be done to validate the results of this study.

Antiarrhythmic efficacy of penticainide and comparison with disopyramide, flecainide, propafenone and mexiletine by acute oral drug testing

The antiarrhythmic efficacy of a new class I agent, penticainide, was evaluated by acute oral drug testing and compared in the same patient population with the efficacy of disopyramide, flecainide, mexiletine and propafenone. Twenty-five patients with high-grade chronic ventricular arrhythmias entered the study. During acute oral drug testing, penticainide (7 mg/kg) was effective (more than 90% reduction in ventricular premature complexes and complete abolition of class 4A and 4B arrhythmias) in 17 of 25 subjects (68%). The mean plasma level of the drug at 90 minutes was 4.4 ± 1.9 μg/ml; at the same time increases in the PQ interval (from 168 ± 27 to 189 ± 31 ms, p < 0.0001) and QRS duration (from 89 ± 14 to 96 ± 18 ms, p < 0.001) were observed, the QTc was slightly but not significantly shortened in the overall population; however, in the subgroup with a basally prolonged QTc (n = 8), a significant reduction was observed (from 456 ± 8 to 440 ± 18 ms, p < 0.02). No adverse effects were reported. The antiarrhythmic efficacy of the other drugs tested in the same population was: disopyramide, 12 of 19 (63%); flecainide, 13 of 24 (54%); propafenone, 13 of 24 (54%); and mexiletine, 7 of 20 (35%). Penticainide appears to be a well-tolerated and effective compound of potential value for treatment of ventricular arrhythmias.

Efficacy and tolerance of ethmozine ® (moricizine HCl) in placebo-controlled trials

To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs > 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.

Combination of tocainide and quinidine for better tolerance and additive effects in patients with coronary artery disease

The efficacy and tolerance of tocainide used alone and in combination with quinidine were studied in 20 patients with coronary artery disease and frequent (greater than 30/h) ventricular premature complexes. Holter electrocardiographic monitoring was performed at baseline and during therapy with tocainide alone, quinidine alone and a combination of tocainide and quinidine. During single drug therapy, the dose of tocainide was 1,680 +/- 437 mg/day and that of quinidine was 1,340 +/- 235 mg/day. During combination therapy, with smaller doses of tocainide (1,350 +/- 394 mg/day) and quinidine (1,060 +/- 268 mg/day) in many patients, no patient had side effects. At baseline before therapy, the mean ventricular premature complexes/h were 629 +/- 567, couplets/h were 23.9 +/- 29.7 and nonsustained ventricular tachycardias/24 h were 60.5 +/- 152.2. Compared with baseline values (100%), the frequency of ventricular premature complexes was reduced to 33 +/- 44% with quinidine, 39 +/- 30% with tocainide and 10 +/- 16% with combination therapy (p less than 0.01 for combination versus quinidine or tocainide alone; p = NS for quinidine versus tocainide). Individually, an effective regimen (greater than 83% reduction of ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 3 (15%) of 20 patients receiving tocainide alone, in 6 (30%) receiving quinidine alone and in 16 (80%) receiving combination therapy (p less than 0.01 for tocainide versus combination, quinidine versus combination; p = NS for tocainide versus quinidine). Thus, the antiarrhythmic effects of quinidine and tocainide are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous variability of ventricular arrhythmias in patients at increased risk for sudden death after acute myocardial infarction: Consecutive ambulatory electrocardiographic recordings of 88 patients

The Cardiac Arrhythmia Pilot Study, sponsored by the National Heart, Lung, and Blood Institute, is a multicenter, prospective, randomized, double-blind trial designed to identify patients having 10 or more ventricular premature complexes (VPCs) per hour within 6 to 60 days of acute myocardial infarction. The present investigation selected patients after acute myocardial infarction who had ambulatory electrocardiographic qualifying arrhythmia for CAPS. An additional baseline electrocardiogram was recorded before enrollment in the study to assess baseline spontaneous variability of VPCs. A total of 88 patients (15 women, 73 men, aged 57 ± 10 years) were studied. The 43 patients (49%) receiving β-blocking drugs were included because the dose was not altered between the 2 consecutive electrocardiographic recordings. This investigation shows that a 95% reduction in VPCs is required to document a significant drug effect rather than variability alone if 1 day of control and 1 day of treatment electrocardiographic recording are compared. Similarly, based on 1 day of electrocardiographic recording before and after antiarrhythmic therapy, a 1,780% increase in VPC frequency is required to establish “arrhythmia aggravation” from an antiarrhythmic drug rather than from variability alone based on a 95% confidence interval. Variability of ventricular arrhythmias is independent of left ventricular function, whereas patients taking β-blocking therapy tend to have greater VPC variability (p = 0.052), even though VPC frequencies were lower (59 ± 19 vs 138 ± 31 VPCs/hour, p < 0.006) than those not taking β-blocking drugs.

Comparison of programmed stimulation and Holter monitoring for predicting long-term efficacy and inefficacy of amiodarone used alone or in combination with a class 1A antiarrhythmic agent in patients with ventricular tachyarrhythmia

The values of two Holter ambulatory electrocardiographic monitoring criteria and one programmed stimulation efficacy criterion reported to be predictive of the efficacy of amiodarone were compared in 70 patients taking amiodarone for sustained ventricular tachyarrhythmias. At baseline, all patients had ventricular tachycardia inducible by programmed stimulation. After amiodarone loading (935 +/- 271 mg for 16 +/- 7 days), efficacy was determined by a programmed stimulation criterion (ventricular tachycardia no longer inducible or less than or equal to 15 beats) and two Holter monitoring criteria (Holter I = greater than or equal to 85% reduction of ventricular premature complexes and abolition of couplets and triplets in 64 patients who had greater than or equal to 10 ventricular premature complexes/h or couplets or triplets or both before therapy; Holter II = abolition of triplets in 41 patients who had triplets before therapy). Amiodarone was effective in 12 of 70 patients by the programmed stimulation criterion, in 49 of 64 patients by Holter criterion I and in 37 of 41 patients by Holter criterion II. In assessing efficacy of amiodarone, programmed stimulation and Holter criteria were discordant in 69% of patients or more (p less than 0.001). There were 16 recurrences or sudden deaths during the entire follow-up period (19 +/- 19 months). Arrhythmia-free survival rates at 24 months of patients with efficacy and inefficacy by each criterion, respectively, were 90 and 78% by programmed stimulation, 84 and 62% by Holter criterion I (p less than 0.05) and 73 and 50% by Holter criterion II (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Value of holter monitoring in predicting long-term efficacy and inefficacy of amiodarone used alone and in combination with class 1A antiarrhythmic agents in patients with ventricular tachycardia

The value of two reported and two new ambulatory electrocardiographic (Holter) criteria was studied in 80 patients taking amiodarone for refractory recurrent sustained ventricular tachycardia. In the 80 patients, the four Holter criteria were as follows: I-85% or greater reduction of ventricular premature complexes and abolition of couplets and nonsustained ventricular tachycardia in 74 patients who had 10 or more ventricular premature complexes/h, or any couplets or nonsustained ventricular tachycardia/24 hours at baseline; II-abolition of nonsustained ventricular tachycardia in 51 patients who had nonsustained ventricular tachycardia at baseline; III-85% or greater reduction of ventricular premature complexes and abolition of nonsustained ventricular tachycardia in 64 patients who had 30 or more ventricular premature complexes/h at baseline; and IV-85% or greater reduction of ventricular premature complexes and abolition of nonsustained ventricular tachycardia in 73 patients who had 10 or more ventricular premature complexes/h at baseline. Amiodarone was judged effective in, respectively, 51 of 74, 44 of 51, 51 of 64 and 61 of 73 patients by criterion I, II, III or IV. During the follow-up period (19 +/- 20 months), there were 19 instances of recurrence of ventricular arrhythmia or sudden death. Actuarial arrhythmia-free survival rate at 24 months was 84, 74, 86 and 85%, respectively, in patients with efficacy by criterion I, II, III or IV and 61, 43, 48 and 39%, respectively, in patients with inefficacy (p less than 0.015 for all). Many patients with efficacy by Holter criteria, however, had a recurrence of arrhythmia, suggesting insensitivity of these Holter criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Propafenone: A New Anti arrhythmic for Treatment of Chronic Ventricular Arrhythmias

Propafenone is a new anti arrhythmic agent with primarily membrane‐stabilizing action. Three U.S. controlled double‐blind cross‐over studies demonstrated the efficacy of propafenone in suppressing ventricular premature complexes (VPCs), including repetitive forms: 67–83% of patients had greater than 80% reduction of VPCs, 62% achieved greater than 90% reduction of couplets and 80%–100% achieved 200% abolition of ventricular tachycardia runs. Other studies showed that propafenone is effective in controlling ventricular arrhythmias refractory to conventional anti arrhythmic agents. Propafenone is at least as effective as these agents. Long‐term sustained efficacy of propafenone was shown in some preliminary studies. Because of the variation in individual response to the drug, therapy should be individualized for each patient. Propafenone is well tolerated: side effects of propafenone are few and involve mostly the cardiac conduction system. Propafenone would be a significant addition to the anti arrhythmic armamentarium.

Electrophysiologic effects and clinical efficacy of mexiletine used alone or in combination with class IA agents for refractory recurrent ventricular tachycardias or ventricular fibrillation

The electrophysiologic effects and clinical efficacy of mexiletine used alone or in combination with class IA agents were studied in 35 patients with recurrent sustained ventricular tachycardia (VT) or ventricular fibrillation refractory to nonexperimental antiarrhythmic agents. At baseline before therapy, all patients had inducible VT by programmed stimulation (1 to 3 extrastimuli) and frequent (at least 30/hour) ventricular premature complexes (VPCs) during Holter monitoring. Mexiletine therapy was effective by programmed stimulation (VT no longer inducible or 15 or less beats) in 8 and ineffective in 27 patients. Twenty patients were discharged with mexiletine (14 of whom took an additional class IA agent). The discharge regimen was effective by programmed stimulation in 6 of these 20 patients. In 14 patients the discharge regimen was ineffective by programmed stimulation, but all patients had a marked reduction of ventricular ectopic activity (at least 83% reduction of VPCs and abolition of non sustained VT). During the follow-up period of 18 ± 13 months (mean ± standard deviation), 4 patients had recurrences (3 with an ineffective regimen by programmed stimulation and 1 with an effective regimen by programmed stimulation). Arrhythmia-free survival rates at 12 and 24 months were 86% and 77%, as determined by the Kaplan-Meier method, in patients with an ineffective regimen by programmed stimulation, and 80% and 80% in patients with an effective regimen by programmed stimulation (p = 0.979 by log rank test). This nonrandomized study suggests that in selected patients with inducible VT and frequent VPCs at baseline, persistent induction of VT by programmed stimulation during mexiletine therapy (alone or in combination with class IA agents) may not preclude good clinical outcome when it is accompanied by a marked reduction of spontaneous ventricular ectopic activity.

Is Programmed Stimulation of Value in Predicting the Long-Term Success of Antiarrhythmic Therapy for Ventricular Tachycardias?

We studied the value of programmed stimulation in assessing the efficacy of antiarrhythmic agents in 52 patients with sustained ventricular tachycardia. All patients in this nonrandomized study had ventricular tachycardia inducible by programmed stimulation and also had frequent ventricular premature complexes (greater than or equal to 30 per hour) on Holter-monitor recordings before therapy. The efficacy of antiarrhythmic agents was assessed by both programmed stimulation and Holter recordings during serial drug testing. A regimen was deemed effective according to the programmed-stimulation criteria in 25 patients (Group 1). Twenty-seven patients in whom tachycardia could still be induced during programmed stimulation despite extensive drug trials were discharged on a regimen that caused a marked reduction of ventricular premature complexes according to Holter monitoring (Group 2). In 23 patients no effective drug regimen was identified by either set of efficacy criteria, and these patients were excluded from the present analysis. Follow-up lasted 18.6 +/- 13.9 months. Rates of arrhythmia-free survival at 12 and 24 months were 88 percent and 72 percent, respectively, in Group 1 and 84 percent and 75 percent in Group 2 (P = 0.637). We conclude that demonstration of antiarrhythmic efficacy by programmed stimulation predicts a good clinical outcome, that inefficacy as shown by the programmed-stimulation protocol used in this study may not preclude a good outcome if there is a marked reduction of spontaneous ventricular premature complexes on Holter monitoring, and that randomized trials should be conducted to validate the results of this observational study.

Effectiveness of low-dose nadolol for ventricular arrhythmias

To determine the minimal effective dose of nadolol to suppress frequent ventricular premature complexes (VPCs), 23 patients with at least 30 VPCs/hour on 2 baseline 24-hour Holter recordings were studied. The initial dose of nadolol was 10 mg/day orally, and this dose was doubled at weekly intervals until arrhythmia suppression was achieved, adverse effects appeared, or a maximal dose of 160 mg/ day was reached. After each dose level a 24-hour ambulatory Holter monitor was recorded. A pharmacokinetic trial was conducted in patients who responded to nadolol treatment. Frequent VPCs were suppressed at least 75% by nadolol in 11 of 23 patients (48%) and the minimal effective dose was 10 mg/day in 3 patients, 20 mg/day in 4, 40 mg/ day in 3 and 80 mg/day in 1 patient. At these doses, minimal steady-state levels of nadolol in serum (Cmin) ranged from 3.9 to 47.0 ng/ml, and these serum concentrations were proportional to the oral dose of nadolol (r = 0.753, p < 0.001). No relation, however, was observed between Cmin levels and percent reduction of VPCs. Cmin and heart rate changes were comparable between responders and nonresponders, suggesting that the degree of β blockade was similar between these 2 groups. Adverse reactions were noted in 6 patients, and 2 had an asymptomatic increase in the frequency of VPCs and 1 patient an increase in beats of ventricular tachycardia. This study details the importance of selecting an individualized dose for nadolol for control of ventricular arrhythmias; in more than half of the patients doses of 20 mg/day or less were effective.

Discordance between ambulatory monitoring and programmed stimulation in assessing efficacy of mexiletine in patients with ventricular tachycardia

Programmed electrical stimulation (PES) and 24-hour Holter monitoring were compared in 30 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) before and during treatment with mexiletine. Before treatment, all patients had ≥30 ventricular premature complexes (VPCs)/hr and 22 patients had nonsustained VT on Holter. All had inducible sustained VT by PES (one to three extrastimuli). Mexiletine was effective in only 23% by PES criteria (VT no longer inducible or ≤15 beats in duration and effective in 57%, 57%, and 73% by Holter criteria I, II, and III, respectively (Holter I ≥50% reduction of VPCs, ≥90% reduction of couplets and abolition of nonsustained VT; Holter II ≥83% reduction of VPCs and abolition of VT; Holter III abolition of VT in patients who had VT during baseline Holter). Results of PES and Holter were discordant in 67%, 60%, and 55% (PES vs Holter I, II, and III, respectively). The majority (≥75%) of the discordance occurred due to mexiletine appearing effective by Holter criteria but ineffective by PES criteria (suggesting insensitivity of efficacy by Holter criteria and/or nonspecificity of induced VT during treatment with mexiletine). Conclusions: (1) PES and Holter are discordant in assessing efficacy of mexiletine ( p < 0.05). (2) Efficacy of mexiletine by Holter criteria is easier to achieve than efficacy by PES. (3) The discordance between the two methods, both with very good reported predictive values, calls for randomized clinical follow-up studies to determine sensitivity and specificity of each method in assessing efficacy of mexiletine.

Comparative antiarrhythmic efficacy of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone in patients with severe chagasic myocarditis: Relation with the underlying arrhythmogenic mechanisms

The antiarrhythmic effects of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone were compared in 14 patients with chagasic myocarditis. Drugs and placebo were administered orally in the following order: placebo and verapamil, placebo and 17-monochloracetylajmaline, placebo and mexiletine (1 week each) and placebo and amiodarone (4 weeks each). A 24 hour ambulatory electrocardiographic recording was obtained after administration of each placebo and drug. Verapamil had no effect on the number of ventricular premature complexes, ventricular couplets and runs of ventricular tachycardia. 17-Monochloracetylajmaline did not reduce the number of ventricular premature complexes and ventricular couplets but caused a moderate reduction in runs of ventricular tachycardia. Mexiletine failed to significantly reduce ventricular premature complexes but caused a moderate decrease in both ventricular couplets and runs of ventricular tachycardia. Amiodarone was the only one of the four drugs that caused a substantial reduction of ventricular premature complexes (logarithmic mean 97.8%; p less than 0.001), total suppression of runs of ventricular tachycardia in 11 of 11 patients and suppression of ventricular couplets in 8 of 14 patients and a significant reduction in the remaining 6 patients. The much greater efficacy of amiodarone as compared with the two sodium channel modifiers (17-monochloracetylajmaline and mexiletine) and one calcium channel blocker (verapamil) suggests that its potent antiarrhythmic activity is probably related to other peculiar and still undefined electrophysiologic and pharmacologic properties.

Discordance between ambulatory monitoring and programmed stimulation in assessing efficacy of class IA antiarrhythmic agents in patients with ventricular tachycardia

Concordance between programmed stimulation and 24 hour ambulatory electrocardiographic (Holter) monitoring was studied in 54 patients with sustained ventricular tachycardia during 84 therapeutic trials with class IA antiarrhythmic agents. During baseline studies before treatment, all patients had frequent (greater than or equal to 30/h) ventricular premature complexes on Holter recordings and sustained ventricular tachycardia inducible by one to three extrastimuli. During treatment, programmed stimulation and Holter monitoring were repeated. Efficacy of treatment determined by programmed stimulation (ventricular tachycardia no longer inducible or nonsustained) was compared with three Holter criteria of efficacy: I = 83% or more reduction of ventricular premature complexes and abolition of ventricular tachycardia; II = 50% or more reduction of ventricular premature complexes and 90% or more reduction of couplets and abolition of ventricular tachycardia; III = abolition of ventricular tachycardia in patients with ventricular tachycardia during a baseline Holter recording. Treatments were judged effective by programmed stimulation criteria in only 25% of cases but in 51, 63 and 75% of cases by Holter criterion I, II and III, respectively. Results of programmed stimulation and Holter monitor were discordant (effective by one criterion but ineffective by the other) in 50% of cases using Holter criterion I, in 54% using Holter criterion II and in 61% using Holter criterion III. In the majority of discordant results, treatments appeared efficacious by Holter criteria but ineffective by programmed stimulation criteria, suggesting insensitivity of efficacy by Holter criteria or nonspecificity of induced ventricular tachycardia during treatment, or both.