Ventricular Ectopic Depolarizations Research Articles

Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy

Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the "guarded-receptor" model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals < 600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 +/- 2% in these patients without side effects. In the "nonresistant" but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with "fast-off" and one with "slow-off" kinetics, which may provide a general rationale for choosing drug combinations.

Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy

Summary: Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals <600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 ± 13% for 400 and 800 mg/day ethmozin and 18 ± 12 and 55 ± 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 ± 2% in these patients without side effects. In the “nonresistant” but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with “fast-off” and one with “slow-off” kinetics, which may provide a general rationale for choosing drug combinations.

Part IV: Class II, Class III, and Class IV Antiarrhythmic Drugs, Comparative Efficacy of Drugs, and Effect of Drugs on Mortality — A Review of Their Pharmaco kinetics, Efficacy, and Toxicity*

Part IV: Class II, Class III, and Class IV antiarrhythmic drugs, comparative efficacy of drugs, and the effect of drugs on mortality — review of their pharmacokinetics, efficacy, and toxicity. This part reviews the Class II antiarrhythmic agents that share the property of beta adrenergic antagonism, but include several drugs with other unique features. Also reviewed are the Class III agents, which prolong the action potential duration, with a focus on amiodarone. The Class IV agents, which antagonize the calcium channel, are reviewed. Finally, this part reviews the comparative efficacy of antiarrhythmic agents for treatment of ventricular ectopic depolarizations and examines their effect on mortality.

Pirmenol: An antiarrhythmic drug with unique electrocardiographic features—a double‐blind placebo‐controlled comparison with quinidine

Previous reports have stated that pirmenol is a Class IA antiarrhythmic drug that prolongs the QT interval, but did not use computerized electrocardiography. We randomized 18 patients with frequent ventricular ectopic depolarizations to pirmenol (8 patients) or quinidine (10 patients). Pirmenol was effective and tolerated for suppression of arrhythmia in all 7 patients treated (1 patient withdrew for personal reasons) but quinidine was effective and tolerated for 4 weeks in only 5 of 10 patients (p less than 0.05). Using computerized 12-lead electrocardiography, the mean change in PR interval from placebo to treatment was 5 +/- 18 ms for quinidine and 5 +/- 11 ms for pirmenol (p = NS). The mean change in QRS interval was 5 +/- 14 ms for quinidine and 10 +/- 5 ms for pirmenol (p = NS). The mean change in QT interval was 46 +/- 30 ms for quinidine and 8 +/- 9 ms for pirmenol (p less than 0.01) and the mean change in JT interval was 41 +/- 36 ms for quinidine and -2 +/- 10 ms for pirmenol (p less than 0.01). After the double-blind phase, 4 quinidine patients had computerized electrocardiographic intervals measured on pirmenol; the above findings were confirmed. These electrocardiographic features of pirmenol clearly distinguish it from quinidine, the prototype Class IA drug. However, pirmenol has minimal effect on the PR and QRS intervals, and thus does not appear to be a Class IC drug either. Although its electrocardiographic features are closest to Class IB, its electrophysiology in isolated cells and its antiarrhythmic and side effect profile are atypical for a IB agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac arrhythmias identified in horses with duodenitis/proximal jejunitis: Six cases (1985-1988)

Summary During a 3½-year period, cardiac arrhythmias were identified in 6 of 67 horses diagnosed with duodenitis/proximal jejunitis (dpj). Arrhythmias were detected by auscultation of irregular cardiac rhythm and subsequently were characterized by electrocardiographic evaluation. Arrhythmias included frequent second-degree atrioventricular block, ventricular ectopic depolarizations, and atrioventricular conduction disturbance. In 4 horses, arrhythmias resolved with recovery from the primary problem. One horse died suddenly 66 hours after admission, and another was euthanatized at 72 hours after admission. Clinical and laboratory data from horses with dpj and cardiac arrhythmias (group l) were compared with findings for horses with dpj and without arrhythmias (group 2). Group-1 horses had significantly (P &lt;0.05) higher serum bicarbonate concentration and serum creatine kinase activity. Normal sinus rhythm returned in all 4 group-1 horses that recovered from dpj, suggesting a causal relationship between dpj and the arrhythmias. Two group-1 horses were necropsied, and both had myocarditis. The cause of these lesions was not determined.

A comparison of antiarrhythmic drugs for the suppression of ventricular ectopic depolarizations: A meta-analysis

This article reports the results of a meta-analysis of the effectiveness of antiarrhythmic drugs for the suppression of ventricular ectopic depolarizations. We analyzed 97 published articles that referred to a total of 27 drugs and contained data from 2989 patient-treatment trials; our goal was to determine the number of patients responding to therapy, defined as ≥ 80% suppression of ventricular ectopic depolarizations. By means of logistic regression we tested the effect of 10 clinical and experimental variables on the likelihood of response to therapy. The likelihood of a drug response was significantly affected by the following six variables: increased by the use of dose titration ( t = 3.59, p < 0.0001), increased by the use of a higher daily dose ( t = 3.21, p < 0.0001), decreased by older age ( t−2.67, p = 0.004), decreased by the use of blinding ( t = −2.28, p = 0.011), increased by treating more male patients ( t = 1.72, p = 0.043), and decreased by the presence of cardiovascular disease ( t = −1.52, p = 0.064). Incorporating these six variables into our logistic regression model, we adjusted the response rate in each published study and calculated the mean response and standard error for each drug. Of the drugs tested in at least 100 patients, the most effective were amiodarone (estimated response rate 90%), encainide (80%), flecainide (79%), and propafenone (74%). Class IC drugs were significantly more effective than class IB and II drugs ( p < 0.05). With the exception of lorcainide and moricizine, class IC drugs were also more effective than class IA drugs ( p < 0.05). Amiodarone was significantly more effective than all drugs except encainide and flecainide ( p < 0.05). We found no significant differences among the response rates to class IA, IB, and II drugs. Whereas several patient and study characteristics affect the likelihood of response to antiarrhythmic drugs, class IC drugs and amiodarone are significantly more effective than other drugs in suppressing ventricular ectopic depolarizations.

CLASS IA AND CLASS IB ANTIARRHYTHMIC DRUGS — A Review of Their Pharmacokinetics, Electrophysiology, Efficacy, and Toxicity

Class 1A agents share the electrophysiologic property of slmuing of Vmax of phase 0 of the action potential and moderate prolongation of the action potential duration and refractoriness. Their electrocardiographic effect in therapeutic doses is to prolong the QTc. interval due to prolongation of the JTc interval. The PR and QRS intervals are not prolonged in therapeutic doses. This group of agents contains the standard antiarrhythmic agents released prior to 1984. The older drugs in this group wilt be reviewed only briefly in this report. Their effect on suppression of ventricular ectopic depolarizations will be reviewed for comparison with the newer agents.

Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.

To investigate the mechanisms of ventricular arrhythmia suppression by propranolol, we determined the antiarrhythmic efficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-propranolol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (greater than or equal to 80% VED reduction), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920 +/- 360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858 +/- 681). For the entire group, the QTc interval shortened by 4 +/- 4% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta-blockade, racemic propranolol was then administered in dosages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was effective via a non-beta-mediated action. By contrast, in 5/8 patients racemic propranolol also suppressed VEDs. We conclude that propranolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor-mediated effects.

Antiarrhythmic Drug Therapy for Suppression of Ventricular Arrhythmia: Experience with 122 Patients Treated for Two Years

Although there are many reports of the short-term effectiveness of antiarrhythmic drugs for suppression of ventricular ectopic depolarizations, there are less data available on the long-term use of these drugs. We treated 122 patients for up to 2 years with antiarrhythmic drugs for suppression of frequent ventricular ectopic depolarizations. The percent suppression of ventricular ectopic depolarizations and nonsustained ventricular tachycardia for each drug was determined at 1, 3, 6, 12, 18, and 24 months of therapy. Among 33 patients treated with flecainide, the mean suppression of ventricular ectopic depolarizations (average of all data during 24 months) was 93 +/- 17% and of nonsustained ventricular tachycardia was 97 +/- 7%. In 27 patients treated with encainide, the mean suppression of ventricular ectopic depolarizations was 88 +/- 18% and of ventricular tachycardia was 95 +/- 16%. Among 26 patients treated with propafenone, the mean suppression of ventricular ectopic depolarizations was 77 +/- 32% and of ventricular tachycardia was 93 +/- 15%. For the 20 patients treated with moricizine, the mean suppression of ventricular ectopic depolarizations was 62 +/- 35% and of ventricular tachycardia was 90 +/- 14%. Among 16 patients treated with amiodarone, the mean suppression of ventricular ectopic depolarizations was 92 +/- 14% and of nonsustained ventricular tachycardia was 99 +/- 3%. In 54 of the 122 patients (44%), the study drug was stopped during 2 years of therapy because of death (2 sudden, 2 unwitnessed and 6 noncardiac), side effects (21 patients), lack or of loss of efficacy (13 patients), and noncompliance (10 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

The development and testing of intravenous dosing regimens: application to flecainide for the suppression of ventricular arrhythmias.

A two-part pharmacokinetic approach was used to prospectively develop and test intravenous flecainide infusion regimens for the acute therapy for ventricular arrhythmias. Initially, each of nine known responders to oral flecainide was given a rapid flecainide infusion to characterize pharmacokinetic parameters and determine the minimum effective concentration for each patient. These data were used to calculate individually appropriate three-stage flecainide infusions of predetermined durations in eight patients. The three-stage infusions (0.15 +/- 0.02 mg flecainide acetate/kg/min for 5 minutes, 0.046 +/- 0.004 mg/kg/min for 60 minutes, and 0.31 +/- 0.05 mg/kg/hr for 5 to 47 hours; mean +/- SE) resulted in 95% +/- 0.1% suppression of ventricular ectopic depolarizations. Based on these results, six additional patients received a uniform infusion regimen (0.1 mg/kg/min for 5 minutes, 0.025 mg/kg/min for 2 hours, and 0.25 mg/kg/hr for 46 hours). Supplemental doses of 0.25 mg/kg were given (four doses per patient). With this protocol, ventricular ectopic depolarizations were 82.6% +/- 8.5% suppressed. Measured plasma flecainide concentrations were not significantly different from those predicted by pharmacokinetic models. A prompt and sustained antiarrhythmic effect was obtained with an intravenous regimen of flecainide determined by a prospective pharmacokinetic approach. However, the dosages developed in this study may have to be modified for patients with impaired cardiac or renal function.

Indecainide for treatment of ventricular ectopic depolarizations: Efficacy, pharmacokinetics, hemodynamic effects and safety

Ten patients were treated with oral indecainide for frequent ventricular ectopic depolarizations during a short-term, dose-ranging, single blind inpatient trial followed by open label long-term therapy for 2 years. During dose ranging, patients received placebo followed by 50, 75 and 103 mg of indecainide three times daily. Eight of the 10 patients achieved ≥80% reduction in ventricular ectopic depolarizations during inpatient therapy. Mean ventricular ectopic depolarizations decreased from 15,792/24 h to 2,357/24 h on optimal dosage (p < 0.01). Nine patients had paired ventricular ectopic depolarizations; four of the nine had ≥99% reduction of these beats. Among seven patients with nonsustained ventricular tachycardia, five had 100% elimination of these events with indecainide and all had ≥90% reduction in these events. Indecainide prolonged the PR interval 44 ± 27 ms (p < 0.0001) and the QRS interval 11 ± 9 ms (p < 0,0901) from baseline without prolongation of the QTc or JTc interval. The mean trough plasma level of indecainide on optimal dosage was 409 ± 173 ng/ml and the mean plasma elimination half-life was 10.3 ± 2.3 h (range 7.1 to 14.2).No adverse hemodynamic effects of indecainide were detected. Side effects during short-term therapy were mild and did not require discontinuation of the drug. Efficacy was maintained for some patients during long-term therapy for 2 years, although five patients discontinued therapy because of loss of efficacy or side effects. Indecainide is a highly effective and well tolerated antiarrhythmic drug for suppression of frequent and repetitive ventricular ectopic depolarizations.

Effects of different paced heart rates on canine coronary occlusion and reperfusion arrhythmias

Little information exists regarding the effect of heart rate on arrhythmias induced by coronary reperfusion. We therefore evaluated the effects of different heart rates on arrhythmias following canine coronary artery occlusion and reperfusion. Dogs were paced at either 350 msec cycle length (171 bpm; n = 30) or 480 msec cycle length (125 bpm; n = 30). They were then subjected to a 20-minute occlusion of the proximal left anterior descending coronary artery, followed by sudden reperfusion. Ligated vessel perfusion bed size (myocardial “at risk”) was measured with monastral blue and red dyes. The indidence of both occlusion and reperfusion arrhythmias correlated with the myocardium at risk. Dogs paced at 171 bpm had more ventricular ectopic depolarizations (371000 beats vs 81000 beats, p < 0.01) and a higher incidence of ventricular tachycardia during occlusion than those paced at 125 bpm (67% vs 33%, p < 0.05). Dogs paced at the faster rate also had a higher incidence of ventricular tachycardia (83% vs 60%, p = 0.08) and ventricular fibrillation (70% vs 40%, p < 0.05) after reperfusion. Thus, heart rate can have a substantial effect on occlusion and reperfusion arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.

The Efficacy of Propafenone for Treatment of Ventricular Ectopic Depolarizations

Propafenone is an effective agent for suppression of chronic ventricular ectopic depolarizations. Complete elimination of nonsustained ventricular tachycardia is achieved in most patients treated with propafenone. The efficacy of propafenone is best correlated with its prolongation of the PR and QRS intervals whereas its plasma level is a poor predictor of therapeutic efficacy. Although serious side effects do occur with propafenone therapy and the drug must be discontinued in some patients, successful therapy of patients for up to four years has been reported.

Low-level exercise testing after myocardial infarction: usefulness in enhancing clinical risk stratification.

Of 866 patients enrolled in our multicenter study, 667 performed a low-level exercise test early after myocardial infarction, most before discharge. Excluding seven patients who died before the test could be considered, there was a 14% 1 year cardiac mortality in 192 patients who did not take the test (150 for medical and 42 for logistic reasons) compared with 5% in those who did (p less than .0001). Of those who took the test, 12% subsequently underwent bypass grafts surgery compared with 14% of those who did not (p greater than .05). Decreased mortality in the year after the infarction in those taking the test was associated with an increase in blood pressure to 110 mm Hg or higher (3% vs 18%; p less than .001), ability to complete the 9 min test (3% vs 8%; p less than .01), and the absence of couplets (4% vs 13%; p less than .05) or any ventricular ectopic depolarizations (4% vs 7%, p less than .05) before, during, or after exercise. Achievement of a blood pressure of 110 mm Hg or higher during exercise in patients with no evidence of pulmonary congestion on the chest x-ray identified a group of 454 patients (70% of those taking the test) with a 1 year cardiac mortality of 1% compared with 13% in the remaining patients (p less than .0001). Logistic models showed that the exercise test contributed independent prognostic information for cardiac death, new infarction, and bypass surgery. Results of low-level exercise testing before hospital discharge combined with clinical features of the infarction can effectively identify patients at low risk for subsequent cardiac mortality.

Prognostic implications of complicated ventricular arrhythmias early after hospital discharge in acute myocardial infarction: A serial ambulatory electrocardiography study

To assess the prevalence and prognostic implications of complicated ventricular ectopic depolarizations (VEDs) after hospital discharge in patients with acute myocardial infarction (AMI), we obtained serial 24-hour Holter recordings in 85 patients during the first 6 weeks after AMI. Recordings were obtained during two coronary care unit time intervals, two hospital ward time intervals, and during four weekly time intervals after discharge. Complicated VEDs were defined as unifocal VEDs ≥ 10 1000 beats for 24 hours, multiform VEDs, pairs, or ventricular tachycardia. At 1 year follow-up, there were nine cardiac deaths (six sudden deaths and three deaths from recurrent AMI). The mean left ventricular ejection fraction at discharge in the cardiac death patients was 29 ± 12% (sudden death patients 24 ± 11% and AMI death patients 40 ± 6%) compared to 49 ± 13% in the survivors ( p < 0.001). Patients with complicated VEDs at discharge (2 weeks after AMI) or during the first 4 weeks after discharge (3 to 6 weeks after AMI) were significantly more likely to have sudden death at follow-up compared to patients without complicated VEDs. Of the six sudden death patients, four (66%) had complicated VEDs at discharge compared to 18 of 68 survivors (26%) ( p < 0.05). One of there patients who died of recurrent AMI had complicated VEDs. No Holter data were obtained at hospital discharge in eight of the survivors. Of the six patients with sudden death at follow up, six (100%) had complicated VEDs on three or more 24-hour Holter recordings during the first 4 weeks after discharge compared to 21 of 76 survivors (28%) ( p < 0.001). We conclude that AMI patients with complicated VEDs at discharge or during the first 4 weeks after discharge are at increased risk for sudden death at follow-up. Moreover, the persistence or appearance of complicated VEDs early after discharge in AMI patients may be a marker of continued or acquired myocardial electrical instability and for increased risk of sudden death at follow-up.

Potassium and magnesium abnormalities: Diuretics and arrhythmias in hypertension

Thiazide diuretics are widely accepted as the cornerstone of antihypertensive treatment programs. Hypokalemia is a commonly encountered metabolic consequence of long-term thiazide therapy but the effect of thiazide on serum magnesium is less well known. Thirty-eight patients (22 low renin, 16 normal renin) with moderate diastolic hypertension were treated with hydrochlorothiazide administered twice a day. The initial daily dose was 50 mg; this was increased at four week intervals to 50 mg, 100 mg, 150 mg, and 200 mg. Dose escalation was discontinued when either normalization blood pressure was attained or the 200 mg dose level was reached. Patients were then maintained with their hydrochlorothiazide dose for 24 weeks of continuous thiazide monotherapy. The serum potassium during the control period was 4.5 +/- 0.2 mmol/liter. During dose escalation and long-term maintenance therapy, the serum potassium and magnesium levels fell in a step wise, dose-dependent fashion. In another 38-patient study, the effects of hydrochlorothiazide therapy (100 mg daily) on the occurrence of premature ventricular contractions were observed during rest as well as during static and dynamic exercise. During rest 0.6 +/- 0.08 premature ventricular contractions per minute (mean +/- SEM) were observed, and during dynamic exercise 0.8 +/- 0.15 premature ventricular contractions per minute. During hydrochlorothiazide therapy (50 or 100 mg per day) premature ventricular contractions per minute were 1.4 and 5.7, respectively. The occurrence of premature ventricular contractions correlated significantly with the decrease observed in serum potassium (r = 0.71, p less than 0.001) and in serum magnesium (r = 0.68, p less than 0.001). Thiazide therapy appears to cause both potassium and magnesium depletion, and decreases in both correlate well with the appearance of ventricular ectopic depolarizations.

The antiarrhythmic activity of meobentine sulfate in man.

Meobentine (sulfate) has antifibrillatory and antiarrhythmic activity in canine models. The antiarrhythmic, pharmacokinetic, and adrenergic neuronal blocking effects of meobentine were assessed in 15 patients with chronic, high-frequency ventricular ectopic depolarizations (VEDs). Eleven of the 15 patients had recurrent nonsustained ventricular tachycardia. The patients were given a series of gradually increasing single doses of meobentine; six received oral meobentine and nine had infusions. The antiarrhythmic efficacy of meobentine was assessed by a comparison of arrhythmia frequency during placebo given on days just prior to meobentine. Oral therapy with meobentine at dosages above 20 mg/kg caused diarrhea, and well-tolerated dosages achieved peak concentrations of 0.69 micrograms/ml (range 0.5-1.0 micrograms/ml). Antiarrhythmic activity was seen in only one patient with oral meobentine. In contrast, intravenous infusions (6.75-34.2 mg/kg) achieved concentrations ranging from 1.3-9.8 micrograms/ml. There was a linear relationship between pseudo-steady-state plasma concentrations and dosage, r = 0.82, p less than 0.01. Antiarrhythmic activity was seen in four of nine patients who received intravenous meobentine over a range of concentrations from 2.5-4.5 micrograms/ml. Four patients developed evidence of adrenergic neuronal blockage (loss of the venous reflex response); two at dosages of 16.2 mg/kg, one at 24.3 mg/kg, and one at 34.2 mg/kg. In one individual (24.3 mg/kg), the adrenergic neuronal blockade was associated with an acute episode of shortness of breath, orthopnea, and cough. With intravenous meobentine, there was a linear relationship between dosage and AUC, and the elimination half-life ranged from 11-27 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of ventricular ectopy with intravenous metoprolol in patients with chronic obstructive pulmonary disease.

Intravenous metoprolol, 0.2 mg/kg, was given to 11 patients with stable, partially reversible chronic obstructive pulmonary disease (COPD) and frequent ventricular ectopic depolarizations (VEDs). The frequency of VEDs during 8 h of continuous ECG recording was reduced from a mean of 214/h to 86/h (p less than .001). Four/11 patients had a greater than 90% reduction in VEDs. There were no adverse clinical effects during the period of drug administration. However, metoprolol produced small declines of 14% in the forced expiratory volume in 1 sec (FEB1) and 21% in the forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25-75). These data suggest that iv metoprolol is effective in reducing the frequency of VEDs in patients with COPD, although the extent of reduction in VEDs shows considerable interindividual variation. Metoprolol can be administered iv without inducing clinical bronchospasm in most patients.

Risk Stratification and Survival after Myocardial Infarction

We assessed the role of physiologic measurements of heart function in predicting mortality after myocardial infarction. Most of the 866 patients enrolled in our multicenter study underwent 24-hour Holter monitoring and determination of the resting radionuclide ventricular ejection fraction before discharge. Univariate analyses showed a progressive increase in cardiac mortality during one year as the ejection fraction fell below 0.40 and as the number of ventricular ectopic depolarizations exceeded one per hour. Only four risk factors among eight prespecified variables were independent predictors of mortality: an ejection fraction below 0.40, ventricular ectopy of 10 or more depolarizations per hour, advanced New York Heart Association functional class before infarction, and rales heard in the upper two thirds of the lung fields while the patient was in the coronary-care unit. Various combinations of these four factors identified five risk subgroups with two-year mortality rates ranging from 3 per cent (no factors) to 60 per cent (all four factors).

Recurrent ventricular tachycardia in the absence of overt heart disease: clinical characteristics and response to drug therapy.

Eight patients, seven of them women, have been followed up for a mean of 8.1 years (range, three to 18) with the uncommon syndrome of recurrent frequent episodes of ventricular tachycardia in the absence of overt cardiac abnormality. The mean age at diagnosis was 25 years (range, 12 to 44). Serious symptoms were common: five patients had syncope, cardiac arrest, and/or cerebrovascular accidents. Multiple measures to characterize this population, including study of symptoms, response to exercise, degree of prematurity of ventricular ectopic depolarizations, and response to antiarrhythmic drugs, showed little uniformity. An individualized approach to therapy, taking into account age and symptoms as well as frequency of arrhythmia, was used. Excellent control of arrhythmia was eventually achieved in four patients, but only after multiple drug trials (mean 5.3, range two to eight trials per patient) had been ineffective. Prognosis in this syndrome is generally good, but serious complications occur frequently enough that vigorous therapy is justified in selected patients.