Repetitive Ventricular Premature Complexes Research Articles

Malignant Purkinje ectopy induced by sodium channel blockers.

Sodium channel blocker (SCB) infusion is used to unmask the electrocardiographic pattern of Brugada syndrome. The test may also induce premature ventricular complexes (PVCs) in individuals without Brugada pattern, the clinical relevance of which is little known. The purpose of this study was to describe the prevalence of short-coupled (Sc) PVCs induced by ajmaline or flecainide in patients with suspected or documented severe ventricular arrhythmias. We reviewed the SCB tests performed in 335 patients with suspected ventricular arrhythmias and structurally normal hearts in 9 centers. ScPVCs were defined as frequent and repetitive PVCs with an R-on-T pattern on SCB tests. Repeated SCB tests wereperformed in 7 patients and electrophysiological mapping of ScPVCs in9. Sixteen patients (8 men; mean age 36 ± 11 years) showed ScPVCs and were included. ScPVCs appeared 229 ± 118 secondsafter the initiation of infusion and displayed coupling intervalsof 288 ± 28 ms. ScPVC patterns were monomorphic in 12 patients, originating from the Purkinje systemin mapped patients. Repetitive PVCs were induced in 15 patients (94%) including polymorphic ventricular tachycardias in 9 (56%). SCB infusionwas repeated 45 (interquartile range 0.6-46) months later and induced identical ScPVC in all. SCB test was the only mean to reveal the malignant arrhythmia in 6 patients. Catheter ablation was performed in 9 patients, resulting in arrhythmia elimination in 8 with a follow-up of 6 (interquartile range 2-9) years. SCB can induce ScPVC, mostly from Purkinje tissue, in a small subset of patients with idiopathic ventricular arrhythmias. Its high reproducibility suggests a distinct individual mechanism.

Sustained Ventricular Tachycardia in Apparently Normal Hearts: Medical Therapy Should be the First Step inManagement.

Sustained monomorphic ventricular tachycardia or repetitive premature ventricular complexes can be seen in patients with structurally normal hearts. Among these types of patients, the prognosis is predominantly benign and the treatment mostly focused on elimination of symptoms rather than improving survival or reduction of mortality. This article focuses on the pharmacologic options for management and compares them with invasive options. Based on the current literature, we demonstrate that medical therapies should be used as first-line management and favored over invasive therapies. Understanding the arrhythmia mechanism is critical in choosing the appropriate medication among the wide variety of antiarrhythmic drugs available.

Sotalol Is More Powerful Than Propranolol in Suppressing Complex Ventricular Arrhythmias.

BACKGROUND: Sotalol has combined type II and type III antiarrhythmic properties. Although the beta-blocking action of sotalol is thought to contribute to its antiarrhythmic actions, few data are available from direct comparative clinical trials with pure beta-blocking drugs. METHODS AND RESULTS: In this double-blind, randomized, multicenter, placebo-controlled, parallel study, we have compared the antiarrhythmic efficacy and safety of treatment with sotalol vs propranolol in 181 patients with organic heart disease and frequent (>30 ventricular premature complexes [VPCs]/h) repetitive ventricular premature complexes. Eighty-seven were randomized to receive sotalol and 94 received propranolol. The demographic and clinical characteristics of the two groups were identical, and the majority of patients had coronary artery disease or hypertensive heart disease. Most patients had a long-standing history (>5 years) of ventricular arrhythmias and, in a significant proportion, antiarrhythmic therapy with other drugs had failed in the past. After withdrawal of all antiarrhythmic drugs and 1 week of placebo, qualified patients were randomized to sotalol (320 mg/day) or propranolol (120 mg/day). patients not achieving adequate response were given higher doses of sotalol (640 mg/day) or propranolol (240 mg/day)At baseline, both groups had comparable frequency of total VPCs/hour (274/h and 255/h for sotalol and propranolol groups, respectively) which was reduced to 71 VPCs/h and 109/VPCs/h, respectively, at the end of phase 1. At final evaluation there was a significantly greater response to sotalol as demonstrated by 80% reduction in VPCs/hour with sotalol compared with only 50% reduction noted in the propranolol group. Adequate therapeutic response was also achieved in a significantly greater percentage of patients on sotalol compared with propranolol (56% vs 29%, P =.02). Sotalol was also superior to propranolol in suppressing the VT events/day during phase 1 (89% vs 78% reduction in VT events/day, P <.05). Sotalol was more effective than propranolol in all subgroups and in patients with heart rate <75 beats per minute. CONCLUSIONS: Sotalol is more powerful than propranolol in suppressing ventricular arrhythmias documented on Holter recordings. The superiority of sotalol appears to be related to its combined class II and class III antiarrhythmic actions.

Quantification of Prevalence of Asymptomatic Ventricular Arrhythmias in Patients with Heart Failure

BackgroundVentricular arrhythmias (VAs) are recorded in many patients with chronic heart failure. The present study was designed to prospectively determine and quantify the prevalence of asymptomatic VAs in this patient population.MethodsOne hundred and two patients, 82 men and 20 women (median age 61 years) with NYHA Functional Class II (n = 50, 49%) and III (n = 52, 51%) heart failure were prospectively assessed with 24‐hour ambulatory ECGs.ResultsRare premature ventricular complexes (PVCs) (&lt;100/24 hours) were observed in 22 (21.6%), moderately frequent (101–1000/24 hours) in 31(30.4%), and frequent (&gt;1000/24 hours) in 49 (48.0%) patients. A significantly greater prevalence of &lt;100 PVCs/24 hours was observed in male compared to female patients (P &lt; 0.03) and in those over 61‐years old compared to younger patients (P &lt; 0.01). There was a significantly greater incidence of &gt;0 repetitive PVCs (RPVCs) per 24 hours and &gt;25 RPVCs/24 hours in patients with low ejection fraction (EF), defined as either ≤0.30 (P = 0.003) or ≤ 0.22 (P = 0.02). The occurrence of VT events was significantly associated with EF ≤ 0.30 (P = 0.007). The prevalence of &gt;100 PVCs/24 hours was significantly higher in patients treated with digoxin (P &lt; 0.02).ConclusionsPVCs are more frequently observed and more frequent in number in patients with heart failure than in normal subjects, and arrhythmia severity correlates with severity of left ventricular dysfunction.

Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia

A combined use of noninvasive techniques and eloctrophysiologic study in the prediction of arrhythmic events was prospectively evaluated in 303 surviving patients of acute myocardial infarction (AMI). The most powerful combination of non-invasive prognostic variables in identifying patients suitable for invasive strategies was also assessed. Patients who had ≥2 variables among left ventricular ejection fraction < 0.4, ventricular late potentials and repetitive ventricular premature complexes (VPCs) were considered eligible for programmed ventricular stimulation. After 15 ± 7 months of follow-up, 19 patients (6%) had an arrhythmic event. Left ventricular dyskinesia (p < 0.00001) and ejection fraction < 0.4 (p < 0.000001), late potentials (p < 0.001), filtered QRS duration ≥106 ms (p < 0.00001), VPCs/hour > 6 (p < 0.05), paired VPCs (p < 0.01), ≥2 runs of unsustained ventricular tachycardia (VT) per monitoring (p < 0.001), heart rate variability index ≤29 (p < 0.00001) and mean RR interval ≤750 ms (p < 0.01) were found to be significant univariate predictors of events. At multivariate analysis, only low left ventricular ejection fraction, prolonged filtered QRS duration, reduced heart rate variability index and detection of ≥2 runs of unsustained VT per monitoring had an independent relation to late arrhythmic events. Of 67 eligible patients, 47 (70%) consented to undergo programmed stimulation. A positive etectrophysiologic study was found to be the strongest independent predictor of events among patients preselected by noninvasive techniques. With a good sensitivity (81%), a combined use of noninvasive tests and electrophysiologic study selected a group of post-AMI patients at sufficiently high risk (event rate 65%) to be considered candidates for interventional therapy. The combination of ≥2 variables among left ventricular ejection fraction < 0.4, filtered QRS duration ≥106 ms and ≥2 runs of unsustained VT was superior to the other ones in identifying high-risk subjects (positive and negative predictive values for arrhythmic events of 44 and 99%, respectively). On the basis of the data, this scheme appears to be the most appropriate for selecting patients suitable for etoctrophysiologic testing and invasive strategies after AMI.

Suppressant effects of conventional beta blockers and sotalol on complex and repetitive ventricular premature complexes

Beta-blocking drugs have been shown to reduce the overall mortality and risk of sudden cardiac death in survivors of acute myocardial infarction. It is not known whether such an effect is mediated by suppression of ventricular premature complexes (VPCs). The circadian rhythmicity of ventricular arrhythmia can also be suppressed by β-blocking drugs, and this may help reduce the risk of sudden cardiac death during the morning hours. Recent studies have also shown that β blockers can provide a safe and effective combination with class IA antiarrhythmic agents when arrhythmias cannot be controlled with class IA agents alone. Sotalol, a nonselective β antagonist, has unique electrophysiologic properties, and several studies have shown it to be more effective than conventional β blockers in suppressing ventricular arrhythmias. However, direct comparative studies of the suppression of VPCs are lacking. In a recent double-Mind, placebo-controlled, parallel study, the antiarrhythmic effects of sotalol and propranolol were compared in 172 patients with >30 VPCs/ hour. After the initial 1-week washout and 1-week placebo period, patients were randomly assigned to either 160 mg of sotalol administered twice daily (76 patients) or 40 mg of propranolol administered 3 times daily (91 patients). Those responding to therapy (decreases >75% VPCs) continued to take these closes, but nonresponders were given higher doses, 320 mg of sotalol twice daily or 80 mg of propranolol 3 times daily, respectively. The baseline mean hourly VPC count, derived from two 24-hour Holter recordings during the placebo phase, was 274 for sotalol and 255 for propranolol patients and was reduced to 54 (80% decrease) for sotalol and 104 (59% decrease) for propranolol-treated patients at 6 weeks (p < 0.002). A significantly greater percentage of patients (56%) responded to sotalol compared with those who responded to propranolol (29%) (p < 0.001). The class III antiarrhythmic activity of sotalol may account for its superiority over propranolol.

Occurrence, characteristics and prognostic significance of early postacute myocardial infarction angina pectoris

To determine the incidence, clinical characteristics and prognostic significance of early spontaneous angina after acute myocardial infarction (AMI), the database involving the 867 participants of the Multicenter Post-AMI Program, who were followed for 1 to 4 years after AMI, was analyzed. Two hundred eighty-six patients (33%) had in-hospital postinfarction angina. During a mean follow-up of 31 months, patients with postinfarction angina were more frequently (p < 0.001) hospitalized for cardiac causes and underwent coronary artery bypass graft surgery; however, their cardiac mortality rates at 1 year (8.4%) and at 4 years (14.3%) were not significantly different from those among patients without postinfarction angina (7.1 and 12.9%, respectively). The only anginal characteristic found to be associated with increased subsequent cardiac mortality (17.9% at 1 year, 39.2% at total follow-up) was high frequency angina (≥1 daily episodes). High frequency angina occurred in a small subset of 28 patients (3.2% of the study population, 9.8% of patients with postinfarction angina). Clinical variables representing higher grades of mechanical dysfunction and electrical instability after infarction were significantly more common among patients with high frequency angina than among those with low frequency angina. Cox survivorship analysis revealed that high frequency angina made a significant contribution to the risk of post-AMI cardiac death (hazard ratio 2.5, p = 0.01), which was independent of the effect of predischarge reduced radionuclide ejection fraction and Holter-recorded frequent or repetitive ventricular premature complexes. Low frequency angina (present in 90.2% of patients with postinfarction angina) did not make a significant contribution to the risk of post-AMI cardiac death (hazard ratio 0.9, p = 0.75).

The cardiac arrhythmia pilot study

Frequent or repetitive ventricular premature complexes (VPCs) occurring soon after acute myocardial infarction are predictors of subsequent mortality independent of left ventricular dysfunction. The Cardiac Arrhythmia Pilot Study (CAPS) is a 10-center study sponsored by the National Heart, Lung, and Blood Institute to determine whether postinfarction ventricular arrhythmias can be satisfactorily reduced for 1 year after acute myocardial infarction. Patients younger than 75 years are screened for arrhythmias 6 to 60 days after acute myocardial infarction. To qualify for CAPS, patients must have at least 10 VPCs or at least 5 runs of 3 to 9 consecutive VPCs in a 24-hour electrocardiographic recording and a left ventricular ejection fraction greater than 0.20. Eligible patients without exclusion criteria are randomized into 1 of 5 treatment tracks (4 active treatment and 1 placebo). Within a treatment track, patients are permitted to change drug and dosage in order to achieve at least 70% reduction in VPC frequency and at least 90 % reduction in runs of VPCs over 1 year of follow-up. In addition to efficacy assessment, adverse effects, particularly proarrhythmic effects, are being monitored. The results in CA PS will be pivotal for deciding whether a fullscale trial to determine whether controlling ventricular arrhythmias will reduce mortality risk is feasible.

Antiarrhythmic efficacy of pirmenol in the treatment of premature ventricular complexes

We assessed the antiarrhythmic effectiveness, therapeutic plasma concentrations and adverse effects of pirmenol in 16 patients with frequent (mean 933 h-1) premature ventricular complexes (PVC). Progressive increase in dose to a maximum of 200 mg twice daily suppressed PVC in a majority of patients. By preset criteria 11 patients (69%) exhibited an effective suppression of PVCs whereas in 5 patients (31%) the suppression was inadequate despite therapeutic plasma concentrations. The responders exhibited an 87% mean reduction of PVCs and a 97% reduction in repetitive PVC. This therapeutic effectiveness was verified against placebo by repetitive 24-hour ECG monitorings recorded in a double-blind cross-over fashion. The plasma trough concentration during the effective dose averaged 1.31 +/- 0.67 mg-1 (SD). The efficacy was maintained with the twice daily regimen despite an elimination half life of 6.3 +/- 1.7 h (SD) but a slight decrease in PVC suppression was observed towards the end of the administration interval. Pirmenol was well tolerated but aggravation of the arrhythmia occurred in one patient who shared an associated excessive prolongation of the Q-T interval, a feature observed with quinidine-like class I agents.

Pirmenol for control of ventricular arrhythmias: Oral dose-ranging and short-term maintenance study

The antiarrhythmic efficacy and safety of oral pirmenol hydrochloride were assessed during a controlled, dose-ranging and short-term maintenance study in 12 patients with frequent (> 480/8 hours) premature ventricular complexes (PVCs). Eleven patients (92%) responded favorably (> 70% PVC suppression) to a trial of different doses. Mean interval (8-hour) suppression of PVC frequency was 95% in these 11 and 86% in the entire group. Twenty-four-hour suppression was similar in responders (88%). Repetitive PVCs were essentially eliminated. The mean effective dose was 316 mg/day (105 mg/8 hours). The average predose (trough) plasma concentration at the end of dose ranging was 1.4 μg/ml and the drug elimination half-life 7.3 hours (n = 12). Of 11 responding patients, 10 completed a 2-week outpatient trial. Pirmenol continued to be effective and tolerated in 8 patients, maintaining an overall average outpatient PVC suppression of 80%. The electrocardiographic intervals were mildly prolonged after multiple dosing (PR +7%, QRS +12%, QTc +8%; all p < 0.01). Blood pressure and heart rate did not change during treatment. The echocardiographic ejection fraction was maintained. Thus, oral pirmenol appears to be effective, conveniently administered and well tolerated as an antiarrhythmic agent for control of ventricular extrasystoles.

A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes

The effectiveness of oral propafenone was evaluated for the treatment of ventricular premature complexes (VPCs) in 12 patients, using a singleblind, dose-ranging trial followed by a double-blind comparison with placebo, and then an open-label, long-term protocol. During dose ranging, 8 of 12 patients achieved ≥ 80 % suppression of total VPCs (mean 83%) (p < 0.01 vs single-blind placebo). Paired VPCs were suppressed ≥ 90 % and ventricular tachycardia was eliminated in 11 of the 12 patients (p < 0.01). The effectiveness of propafenone for treatment of VPCs was confirmed during the double-blind trial (p < 0.05 vs double-blind placebo) and during treatment for 6 months (p < 0.05 vs initial single-blind placebo). Propafenone prolonged the PR interval by 16% (p < 0.01 vs single-blind placebo) and the QRS interval by 18 % (p < 0.001). Left ventricular systolic performance decreased as assessed by 2-dimensional echocardiography (p < 0.01 vs single-blind placebo). Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase of 83 %). Side effects included exacerbation of congestive heart failure (1 patient) and conduction abnormalities (2 patients). Thus, propafenone is effective for treatment of total and repetitive VPCs. Although generally well tolerated, the drug reduces left ventricular systolic function and atrioventricular conduction and increases serum digoxin levels.

Double-blind placebo-controlled evaluation of propafenone in suppressing ventricular ectopic activity

The effectiveness of oral propafenone in treating ventricular premature complexes (VPCs) was assessed with a single-blind dose-ranging trial followed by a double-blind, randomized, crossover comparison of propafenone and placebo. Patients subsequently were treated with propafenone for up to 24 months. During dose ranging, the average of individual percent suppressions was 83% at the largest dose (300 mg/8 hours). During the double-blind trial, the effectiveness of propafenone was confirmed, with 7 of 12 patients achieving greater than or equal to 80% reduction in VPCs (p less than 0.05 versus double-blind placebo study). Propafenone was also effective in controlling couplets and nonsustained ventricular tachycardia. Seven patients were treated with propafenone for 24 months, during which effectiveness continued, with mean suppression ranging from 67 to 79% (p less than 0.05 versus initial single-blind placebo). Propafenone prolonged PR and QRS intervals by 16 and 18%, respectively; these prolongations continued during long-term therapy. Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase 83%). Cardiovascular side effects included congestive heart failure (1 patient) and conduction abnormalities (3 patients). Thus, propafenone was effective in the treatment of total and repetitive VPCs. Side effects were few, but congestive heart failure, conduction disturbances and increases in serum digoxin were observed.

Definition of benign versus malignant ventricular arrhythmias: Targets for treatment

The most important characteristics of arrhythmias that determine the need for treatment are the prevalence and clinical significance of the ventricular arrhythmia. Ventricular arrhythmias occur more frequently with advancing age, severity of heart disease and ventricular hypertrophy. Malignant ventricular arrhythmias are of 3 forms: out-of-hospital ventricular fibrillation (VF), recurrent sustained ventricular tachycardia and torsades de pointes ventricular tachycardia in the long QT syndrome. Each condition has a high 1-year mortality rate. Potentially malignant ventricular arrhythmias are ventricular premature complexes (VPCs) of >10 per hour 10 to 16 days after acute infarction and repetitive VPCs. The most malignant arrhythmias occur with severely depressed ventricular function, but VPCs alone have independent prognostic significance. Benign ventricular arrhythmias occur in patients without known heart disease and do not require treatment. The exact effect of frequent and complex VPC in these patients needs further definition.

Heart rate levels and ventricular ectopic activity during cardiac rehabilitation

The heart rate levels and the incidence and types of premature ventricular complexes (PVCs) during the rehabilitation of 40 patients with coronary artery disease, were compared with those during 24-hour ambulatory monitoring and during a symptom-limited exercise test. Thirty-six patients were studied 3 months or later after a myocardial infarction and four patients were studied after coronary bypass surgery. The last patient suffered from moderate angina pectoris. Peak heart rates during rehabilitation exceeded those during other activities in 34 out of 40 patients. Half of the patients reached even higher heart rate levels during the exercise test. Twenty-three patients had PVC during rehabilitation; frequent, multiform or repetitive PVC occurred in nine of these. During the exercise test, 24 patients had PVCs, while PVCs were observed on the ambulatory tape recording in 34 patients. Frequent, multiform, and repetitive PVCs occurred in eight patients during exercise testing and in 20 patients during monitoring. No relation was found between either the incidence or the type of PVC in individual patients under these three conditions. Thus, selection of patients with a high risk for arrhythmias during rehabilitation is not feasible by either exercise testing or ambulatory tape recording.

Limitations of 24 hour ambulatory electrocardiographic recording in predicting coronary events after acute myocardial infarction

Twenty-four hour Holter electrocardiographic tape recordings were made in 200 survivors of an acute myocardial infarction 1 to 7 days after discharge from the hospital. Patients taking beta adrenergic blocking or antiarrhythmic drugs were excluded. Eighty-nine percent of the patients participated after completion of the Holter tape recording in an ongoing 1:1 placebo-controlled intervention study with a cardioselective beta adrenergic blocking drug. The incidence and grade of ventricular premature complexes in the standard electrocardiogram and Holter tape recording were correlated with subsequent coronary events: sudden death, fatal recurrent myocardial infarction and uncomplicated recurrent myocardial infarction during the 1st year after the myocardial infarction. Frequent, multiform and repetitive ventricular premature complexes were found in 81 percent of the patients. The occurrence of ventricular premature complexes in the standard electrocardiogram showed a positive correlation with repetitive forms during Holter tape recording. Although more coronary events occurred in the patients with more severe forms of ventricular premature complexes, a statistically significant correlation could not be demonstrated because of the relatively small number of patients studied. It is concluded that a greater proportion of patients than hitherto suspected have severe forms of ventricular premature complexes on 24 hour Holler tape recording 1 to 7 days after hospital discharge. Even if a correlation could be demonstrated between ventricular premature complexes and subsequent coronary events the incidence of this rhythm disturbance is so great that the clinical usefulness of this finding may be limited.