Incidence and prognostic significance of inducible ventricular arrhythmias in the early post-infarction phase

To identify patients at risk of sudden cardiac death or sustained ventricular tachycardia (VT) after recent acute myocardial infarction, 100 patients younger than 70 years (80 male, 20 female; 47 anterior wall infarction, 53 inferior wall infarction) were studied prospectively. 25 days (mean) after onset of myocardial infarction, programmed ventricular stimulation was performed, including the introduction of single (S2) and double (S2-S3) ventricular extrastimuli both during sinus rhythm and at paced ventricular cycle lengths (S1-S1) of 500, 430, 370, and 330 ms. The end of the protocol was reached as soon as 4 or more consecutive ventricular echo beats (VE) were initiated. Four or more VE were initiated in 46% of patients, 4 to 9 VE in 21%, greater than or equal to 10 VE or sustained VT in 25%. During follow-up (15 +/- 8 months), 5 patients died suddenly (less than or equal to 1 h), and 5 further patients developed spontaneous sustained ventricular tachycardia. In 3 patients who died suddenly and 4 with spontaneous sustained VT, greater than or equal to 4 VE had been induced by programmed ventricular stimulation (sensitivity 60% and 80% respectively). With regard to sudden cardiac death and spontaneous ventricular tachycardia, the predictive value of a positive test was 15%, that of a negative (normal) test 94%. False negative results occurred in 6%, whereas 85% of all abnormal results had to be regarded as false positive, as these patients did not develop an arrhythmic event during follow-up. Thus patients after recent myocardial infarction frequently have signs of increased ventricular vulnerability during programmed ventricular stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-response range of encainide for benign and potentially lethal ventricular arrhythmias

A multicenter, 2-week, double-blind, placebo-controlled, parallel group study was performed to determine the dose-response relation of encainide administered 3 times daily and to determine its onset of action. To be included in the study, patients with benign or potentially lethal ventricular arrhythmias were required to have an average of at least 30 ventricular premature complexes (VPCs) per hour on 48-hour Holter monitoring after a 48-hour washout period without antiarrhythmic drug treatment. Patients were randomly assigned to receive either placebo or 10, 25 or 50 mg of encainide 3 times daily (tid) for 2 weeks. Of the 125 patients who entered the study, 122 were available for efficacy analysis. Efficacy was determined using 24-hour Holter monitoring on days 1, 7 and 14. There was no difference in frequency of VPCs or of ventricular tachycardia events in the placebo and 10-mg-tid encainide arms. At doses of 25 and 50 mg of tid, encainide was effective in suppressing VPCs and in reducing the number of episodes of ventricular tachycardia. A positive dose-response relation was identified. The onset of effect of encainide was apparent at 3 hours and lasted for 24 hours with tid dosing. No difference in on-therapy conditions were found among the 4 study arms. No patients were discontinued from the study because of electrocardiographic changes. There was no statistically significant change in vital signs or physical examination data. In 1 patient an elevated serum glucose level developed. No symptomatic proarrhythmic events occurred and none required discontinuation of study medication.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bepridil hydrochloride for treatment of benign or potentially lethal ventricular arrhythmias

To define the efficacy and safety of a new once-a-day calcium antagonist, bepridil, 21 patients with frequent ventricular premature complexes (VPCs) underwent a 14-day inpatient monitored trial. After Holter monitoring during placebo administration, patients underwent 2 days of a loading dose of bepridil followed by 12 days of bepridil, 400 mg/day. Holter monitoring during therapy showed that 10 patients (48%) had more than a 70% reduction in VPC frequency and 8 of 16 patients (50%) at least a 95% reduction in frequency of nonsustained ventricular tachycardia. Gastrointestinal and central nervous system side effects considered to be mild occurred in 13 patients (62%). One patient had an asymptomatic increase in VPC frequency and another had sustained ventricular tachycardia associated with a loading dose of 900 mg of bepridil. Thus, bepridil has moderate antiarrhythmic efficacy in patients with ventricular arrhythmias, but further definition of its potential for causing proarrhythmia must be determined.     

Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias

Classification of ventricular arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents--the beta-adrenergic blocking drugs--have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined. beta blockers are efficacious in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. beta blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the beta blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of greater than 75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider beta blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation.     

Natural history of potentially lethal ventricular arrhythmias in patients treated with long-term antiarrhythmic drug therapy

To examine the natural history of long-term anti-arrhythmic therapy in patients with benign and potentially lethal ventricular premature complexes (VPCs), 28 patients with initial efficacy with moricizine (greater than 75% suppression of baseline mean VPCs/hr and greater than 90% suppression of repetitive VPCs) were prospectively followed for 1 to 56 (mean +/- standard deviation 25 +/- 17) months. Patients were examined during baseline placebo, anti-arrhythmic drug therapy and intermittent pulsed-placebo reexamination periods. The mean VPCs of all patients at baseline entry were 233 +/- 47 VPCs/hr, and after moricizine therapy 14 +/- 4 VPCs/hr. Follow-up demonstrated that antiarrhythmic efficacy decreased to 75% at 12 months and to 62% at 24 months. Loss of antiarrhythmic drug efficacy most commonly occurred as a "transient" event (10 patients [36%]), and efficacy was spontaneously reestablished without a change in antiarrhythmic therapy. In contrast, increased dose titration of moricizine was necessary to reestablish antiarrhythmic suppression efficacy in 4 patients (14%), and 4 patients (14%) lost antiarrhythmic drug responsiveness during follow-up. Spontaneous decrease in baseline VPCs resulted in discontinuation of antiarrhythmic therapy in 3 patients, and increase in baseline VPCs was associated with a loss of antiarrhythmic response in 2 patients. Late proarrhythmic effects (2 patients, 7%), delayed side effects necessitating drug withdrawal (6 patients, 21%) and medical events (4 patients, 14%) occurred during 56 months of follow-up. Individual serum moricizine levels remained in the therapeutic range throughout the study and did not correlate with changes in antiarrhythmic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 greater than 75% reduction in ventricular premature complexes combined with a greater than 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 greater than 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.     

Comparative efficacy and safety of oral tocainide and quinidine for benign and potentially lethal ventricular arrhythmias

The antiarrhythmic efficacy and safety of oral tocainide hydrochloride and quinidine sulfate were compared in a double-blind, 3-center, parallel trial involving 133 patients with benign and potentially lethal ventricular arrhythmias. Baseline demographic, etiologic, functional and ventricular arrhythmia data were not significantly different between the 2 groups. Two weeks of an initial placebo period were followed by 8 weeks of active drug treatment, concluding with 4 weeks of washout. Frequent 24-hour ambulatory electrocardiographic monitoring was used to judge efficacy. Ten of 27 patients (37%) receiving tocainide and 12 of 24 patients (50%) receiving quinidine had a 75% reduction with drug treatment compared with the initial placebo period (p greater than 0.25). Total abolition of ventricular tachycardia occurred in 6 of 16 patients (37%) receiving tocainide and 6 of 13 patients (43%) receiving quinidine (p greater than 0.25). Conditions that required discontinuation of therapy occurred in 18 of 67 patients (27%) receiving tocainide and 16 of 66 (24%) receiving quinidine (difference not significant). More patients had dizziness during tocainide treatment and diarrhea during quinidine treatment. Quinidine caused a prolongation in the QT interval (0.03 second); tocainide caused a slight reduction (0.01 second). No important changes in vital signs or laboratory measurements were observed in left ventricular ejection fraction when measured. Thus, tocainide, the new oral analog of lidocaine, appears to be as safe as quinidine but is slightly less effective in suppressing ventricular arrhythmias.     

Comparative efficacy and safety of oral mexiletine and quinidine in benign or potentially lethal ventricular arrhythmias

The antiarrhythmic efficacy and safety of oral mexiletine hydrochloride and quinidine sulfate were compared at 29 clinical centers in a double-blind, parallel-group trial involving 491 patients with benign or potentially lethal ventricular arrhythmias. Responders were defined as those who had at least a 70% reduction in the frequency of ventricular premature complexes (VPCs) that persisted for 12 weeks, and who experienced no intolerable side effects that required discontinuation of therapy. Of the patients available for analysis, 71 of 232 (31%) in the mexiletine and 73 of 225 (32%) in the quinidine group met these criteria. The dose range used for mexiletine was 200 to 400 mg every 8 hours, and that for quinidine 200 to 400 mg every 6 hours. More than half of the patients in each group were successfully treated with the smallest dose (200 mg every 8 hours mexiletine vs 200 mg every 6 hours for quinidine). Quinidine significantly prolonged the QT interval, whereas mexiletine did not. Proarrhythmic reactions were recorded in 18 of 221 (9%) patients taking quinidine and 10 of 217 (5%) patients taking mexiletine. There was no difference in the incidence of adverse reactions between the 2 groups; in both, the most common side effects were related to the gastrointestinal and central nervous systems. Mexiletine thus represents an alternative to quinidine for the treatment of patients with ventricular arrhythmias.     

Mexiletine. Long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias

The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.     

Incidence of proarrhythmic effects from quinidine in the outpatient treatment of benign or potentially lethal ventricular arrhythmias

To determine the prevalence and importance of proarrhythmic events secondary to the initiation of quinidine therapy in outpatients with benign or potentially lethal ventricular arrhythmias, the data from 360 patients treated with quinidine as part of 3 outpatient drug trials were retrospectively reviewed. These patients had at least 30 ventricular premature complexes per hour during placebo treatment and had no evidence of unstable clinical states, hypokalemia, digitalis toxicity, atrial fibrillation or a prolonged QT interval (longer than 0.50 second). The quinidine dose varied from 200 to 400 mg 4 times a day for 2 to 4 weeks. Proarrhythmic effect was defined on Holter monitoring as a 400% increase in frequency of ventricular premature complexes, the presence of new ventricular tachycardia not previously identified or a 10-fold increase in the number of beats of ventricular tachycardia. There was no difference in the demography, response to quinidine therapy or side effects on quinidine among the 3 trials. Six of 360 patients (2%) had a proarrhythmic response and none of these patients had hemodynamic symptoms, required hospitalization or died from the proarrhythmic event. Thus, quinidine can be safely initiated to outpatients who meet the inclusion criteria cited herein.     

The clinical significance of ventricular arrhythmias after myocardial infarction

Based on a sound foundation of data in thousands of patients who underwent ambulatory ECG recording after myocardial infarction, it is clear tht ventricular arrhythmias are harbingers of sudden cardiac death. Ambulatory electrocardiography, usually performed for 24 hours, continues to be the standard by which clinicians can identify patients at risk for sudden cardiac death after acute myocardial infarction. Ideally, this test should be performed in the late hospitalization phase of acute myocardial infarction, usually 1 to 2 days prior to discharge from the hospital, and the results made known to the clinician prior to the patient's departure from the hospital. Although performed less frequently, low-level exercise testing prior to discharge from the hospital has been shown in some studies to be of prognostic value in defining a group at high risk for sudden cardiac death. This test offers the additional benefit of allowing the clinician to more knowledgeably prescribe an exercise regimen after hospitalization. The specific role of electrophysiologic testing is presently under clinical investigation. At present, only patients with documented spontaneous sustained ventricular tachycardia or sudden cardiac death after myocardial infarction should be candidates for this study. Although it may be possible in the future that electrophysiologic testing will also be used in patients with high-risk arrhythmia detected on ambulatory electrocardiography, at present this is the subject of clinical investigation in academic medical centers and is not recommended as part of standard therapy.     

Prognostic significance of ventricular arrhythmias post-myocardial infarction

Despite improvements in management strategies, ventricular arrhythmias remain important markers of electrical instability and contribute to the identification of patients at increased risk of sudden cardiac death post-myocardial infarction (MI). Over the past 20 years, understanding of pathophysiological mechanisms and implications of various types of ventricular arrhythmias has evolved remarkably. This systematic review details the prognostic significance of ventricular arrhythmias classified by type and time of onset post-MI. Subacute and late premature ventricular complexes are associated with increased mortality independent of left ventricular function. Although nonsustained ventricular tachycardia (VT) in the acute phase post-MI is of questionable significance, later onset heralds poorer prognosis. Sustained monomorphic VT in the acute post-MI phase is associated with infarct extension, heart failure and increased mortality. Extensive wall motion abnormalities, left ventricular dysfunction and aneurysm formation correlate with later postinfarct sustained VT. Inhospital mortality is higher when ventricular fibrillation presents in the acute phase but long term prognosis is not adversely affected.     

Efficacy of amiodarone during long-term treatment of potentially dangerous ventricular arrhythmias in patients with chronic stable ischemic heart disease

Amiodarone was administered orally to 30 patients with chronic stable coronary artery disease and severe ventricular arrhythmias. Control studies revealed frequent (more than 30/hr) ventricular premature beats (VPBs) (27 patients), bigeminy (21 patients), couplets (29 patients), R-on-T phenomenon (14 patients), ventricular tachycardia (16 patients), and ventricular fibrillation (1 patient). Two 24-hour Holter recordings and stress tests were performed before treatment, and an average of 3.6 per patient were done during treatment. Amiodarone caused suppression of all ventricular arrhythmias in 13 (43%) of the 30 patients and suppression of all complex forms and greater than 90% reduction of VPB number in 14 patients (47%) during a follow-up of 12.4 months. The mean dose was 590 mg/day in the 27 responders and 300 mg/day in the three nonresponders. A similar antiarrhythmic response was observed during stress testing. One of the 30 patients died due to massive pulmonary embolism and no arrhythmias were detected. In addition, amiodarone suppressed the occurrence of anginal pain and effort-induced ST changes in 9 of 10 patients and in 11 of 13 patients, respectively. The rate—pressure product and peak heart rate were significantly reduced in all patients. Our results suggest that amiodarone may be ideally suited for treatment of ventricular arrhythmias and for possible prevention of sudden death in patients with ischemic heart disease.     

Clinical implications of new studies in the treatment of benign, potentially malignant and malignant ventricular arrhythmias

For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. Benign arrhythmias occur in the setting of structurally normal hearts and do not require therapy unless associated with debilitating symptoms. Malignant arrhythmias such as sustained ventricular tachycardia or fibrillation deserve aggressive therapy to prevent recurrence. Arrhythmias occurring in the presence of organic heart disease (often ischemic disease) are frequently asymptomatic but prognostically important as a risk factor for sudden death or cardiac arrest. The common empiric practice to treat such arrhythmias (by about 40 to 50% of cardiologists in the United States) needs to be reassessed in the face of the Cardiac Arrhythmia Suppression Trial. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment, and class IB agents (e.g., mexiletine) may be used as alternative or additive therapy. Class IC agents are used as second-line therapy, especially in the setting of ischemic heart disease. Class III therapy with amiodarone is reserved for refractory patients because of potential toxicity. Sotalol, a new class II-III agent, may become a first-line drug. For prognostically important arrhythmias, beta blockers remain the agents of choice, class IC agents are contraindicated, and class IA or IB drugs, or both, should be used conservatively (i.e., only for symptomatic arrhythmias). For symptomatic but benign arrhythmias requiring treatment, beta blockers are safe although not always effective. Class IA, IB and IC agents may then be considered. In these patients, the proarrhythmic potential of quinidine and class IC agents remains a concern.(ABSTRACT TRUNCATED AT 250 WORDS)     

The natural history of benign and potentially malignant ventricular arrhythmias with special reference to nonsustained ventricular tachycardia

Ambulatory ECG recordings are routinely used to identify patients at increased risk of sudden cardiac death and to monitor changes in ventricular arrhythmias during antiarrhythmic drug therapy. The arrhythmia frequency established during the initial baseline has previously been reported to change during a second placebo monitoring period in patients with non-life-threatening ventricular arrhythmias, but the extent to which this applies to patients with nonsustained ventricular tachycardia has not been examined. To extend these observations to patients with potentially lethal ventricular arrhythmias, we studied 53 patients enrolled in one of two investigational antiarrhythmic drug trials that introduced a second single-blind placebo period (placebo-pulse) an average of 16 months after successful arrhythmia suppression. Thirty-eight of the 53 patients had runs of nonsustained ventricular tachycardia recorded during the initial baseline (placebo I) period, with 63% averaging greater than or equal to 10 runs per day. There was a marked reduction in the arrhythmia frequencies between the two placebo periods: 55% for ventricular premature beats, and 77% for pairs (p less than 0.001, respectively). Of the 38 patients with nonsustained ventricular tachycardia, there was a 72% reduction (892 +/- 531 vs 245 +/- 18 runs of VT/day, placebo I vs II; p = 0.0001), with 32% having total suppression of nonsustained ventricular tachycardia during the second placebo period. The results of this trial extend our previous observations of long-term spontaneous changes in arrhythmia frequency to patients with symptomatic, potentially lethal ventricular arrhythmia and support the recommendation for periodic reassessment of baseline arrhythmia frequency to determine the continued need for antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and prognostic significance of hyperkinetic ventricular arrhythmias

Ventricular arrhythmias, mainly ventricular premature beats (VPBs) are omnipresent in the general population. They may be detected or induced by means of different techniques such as routine ECG, ambulatory ECG-monitoring, exercise testing and ventricular stimulation during an intracavitary electrophysiologic study. The prevalence and clinical-prognostic significance of VPBs are highly related to the presence and severity of an underlying heart disease. Simple and complex (bigeminal, multiform, repetitive or R on T) VPBs are much more frequent in cardiac patients than in normal subjects. Acute myocardial infarction (AMI), chronic coronary heart disease (CCHD), cardiomyopathies and mitral valve prolapse are the most common clinical conditions in which VPBs occur. In apparently healthy persons, the presence of VPBs does not seem to indicate a greater risk for the future development of cardiac disease. In patients with AMI frequent, and complex VPBs often precede primary ventricular fibrillation and appear to be directly related to the size of the infarct. In the posthospital phase of AMI, as well as in CCHD, the occurrence of high-grade VPBs usually indicates more advanced degrees of both coronary and left ventricular disease as well as the possibility of cardiac and/or sudden death. In cardiomyopathies and mitral valve prolapse the VPBs do not correlate with either clinical, electrocardiographic, echocardiographic or hemodynamic parameters but their complex patterns appear to be a good indicator of patients with high sudden death risk.     

Prognostic significance of ventricular arrhythmias in coronary patients

Treatment of ventricular arrhythmias in coronary patients is based on the supposition that these forms of rhythm disorders have an adverse prognostic outcome. Initiated by the advent of ambulatory monitoring, several prospective studies have attempted to verify and to specify this assumption. Although the prognostic validity of ventricular arrhythmias could be demonstrated with respect to several prognostic criteria, the statistical significance of these associations was low. One reason for this result seems to be that adequate use has not yet been made of all the informations obtained in ambulatory monitoring. With respect to individual parameters, frequent premature beats and repetitive forms appear to be of particular prognostic importance, whereas the expected role of early premature beats has not been confirmed.     

Calcium antagonists and acute myocardial ischemia: Comparative effects of gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias,epicardial conduction times,and ventricular fibrillation thresholds

Summary The comparative effects of the calcium-antagonists gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, particularly ventricular fibrillation (VF), were assessed in a total of 40 mongrel dogs in two experimental preparations. In part I of the study, changes in the time course of spontaneous ventricular arrhythmias and VF parallel to changes in epicardial conduction following acute coronary artery occlusion lasting 20 minutes and followed by subsequent reperfusion were determined. In part II, repeated coronary artery occlusions (20 min) followed by reperfusion (60 min) were performed, and changes in ventricular fibrillation threshold (VFT) were assessed. Gallopamil proved to be highly effective in preventing ventricular arrhythmias and VF following coronary artery occlusion. Simultaneously, peak epicardial conduction delay was reduced. The ischemia-induced fall in VFT occurring during the first few minutes after occlusion (phase Ia) was significantly reduced. In contrast, nifedipine failed to influence the incidence of ventricular arrhythmias and VF. Following reperfusion, neither drug reduced the incidence of VF nor the associated fall in VFT at the onset of reperfusion. The time course of recovery of epicardial conduction was not affected by either drug. However, the increase in the VFT during the early postreperfusion period was significantly enhanced by both agents. The effects of gallopamil were more pronounced than those of nifedipine. Delayed reperfusion ventricular arrhythmias arising 5 to 10 minutes after release of coronary artery obstruction were significantly reduced by gallopamil whereas nifedipine proved ineffective. The results show that calcium antagonists display direct antiarrhythmic and cardioprotective actions in acute transient myocardial ischemia. The different effectiveness of gallopamil compared to nifedipine can be explained by differences in electrophysiological properties of the drugs. Enhanced ventricular vulnerability following acute transient coronary artery occlusion and subsequent release of coronary artery obstruction, first described by Tennant and Wiggers [1], has been extensively investigated over the past decade in a variety of experimental and clinical settings. However, the basic mechanisms underlying ischemia- and reperfusion-induced ventricular arrhythmias and ventricular fibrillation (VF) have not yet been fully elucidated. Furthermore, the results of pharmacological approaches to prevent ventricular arrhythmic activity are conflicting. The present study aimed to evaluate the antiarrhythmic efficacy of calcium antagonists in acute myocardial ischemia and reperfusion. We have examined the effects of gallopamil and nifedipine on the time course of ventricular arrhythmias during the first 20 minutes after acute coronary artery occlusion and subsequent reperfusion. We have studied the underlying mechanisms by mapping epicardial conduction and by assessing the electrically induced ventricular fibrillation threshold (VFT) both within and outside ischemic areas.     

The effects of metoprolol given early in acute myocardial infarction on ventricular arrhythmias

The effects of metoprolol, administered in the early stages of acute myocardial infarction was studied in 126 patients. Patients were treated in a double-blind randomized fashion, with metoprolol -15 mg, intravenously followed by 100 mg twice daily for 15 days or placebo, with a mean delay of 8.1 hours from onset of symptoms. All patients underwent 24 hour Holter monitoring on days 1, 5 and 15 after randomization. Although there was no antiarrhythmic effect on day 1, metoprolol reduced the number of hours with warning arrhythmias (greater than 30 ventricular ectopics/hour, any R/T ectopics or ventricular tachycardia) on both days 5 (35 +/- 16% vs 8 +/- 11%; P less than 0.05) and day 15 (13 +/- 37% vs 4 +/- 13%; P less than 0.05). Metoprolol also reduced the incidence of ventricular fibrillation and ventricular tachycardia requiring cardioversion -6% vs 0%; P = 0.058. Metoprolol, administered in the early stages of acute myocardial infarction, had an antiarrhythmic effect which was evident only in the later phase of the study.