Faculty Bibliography

Left ventricular aneurysm has been associated with increased mortality rates. The Cardiac Arrhythmia Suppression Trial (CAST) database was used prospectively to assess (1) the prognostic significance of left ventricular (LV) aneurysm after myocardial infarction on mortality rates and (2) the relation of LV aneurysm to ventricular arrhythmias and their suppressibility. All patients in the CAST study were enrolled after myocardial infarction. They had > or = 6 ventricular premature depolarizations (VPDs) per hour and ejection fraction < or = 55%; they were enrolled in the study an average of 96 days after the index myocardial infarction. Of 2494 patients with wall motion data, 164 had LV aneurysm, 600 had only dyskinesis, 913 had only akinesis, and 817 had none of these. Radionuclide scan was used in 39%, two-dimensional echocardiography in 30%, and LV angiogram in 31%. Baseline VPDs and nonsustained ventricular tachycardia were similar in all groups. LV aneurysm patients were more frequently eliminated during open-label titration. The incidence of sustained VT during follow-up was only 2.8% for aneurysm patients, a rate that was similar to the other groups. Patients with LV aneurysm had significantly lower survival rates (82% vs 91%) at 16 months after study entry than those without these wall motion abnormalities (p < 0.005). When survival rates were adjusted for ejection fraction there was still a moderately large hazard ratio (1.34) of LV aneurysm that was not statistically significant (p = 0.18). We conclude that (1) the presence of LV aneurysm does not independently worsen prognosis, and (2) older concepts of LV aneurysm and ventricular arrhythmias must be reevaluated

BACKGROUND. The Cardiac Arrhythmia Suppression Trial (CAST) tested the hypothesis that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarizations in survivors of myocardial infarction would decrease the number of deaths from ventricular arrhythmias and improve overall survival. The second CAST study (CAST-II) tested this hypothesis with a comparison of moricizine and placebo. METHODS. CAST-II was divided into two blinded, randomized phases: an early, 14-day exposure phase that evaluated the risk of starting treatment with moricizine after myocardial infarction (1325 patients), and a long-term phase that evaluated the effect of moricizine on survival after myocardial infarction in patients whose ventricular premature depolarizations were either adequately suppressed by moricizine (1155 patients) or only partially suppressed (219 patients). RESULTS. CAST-II was stopped early because the first 14-day period of treatment with moricizine after a myocardial infarction was associated with excess mortality (17 of 665 patients died or had cardiac arrests), as compared with no treatment or placebo (3 of 660 patients died or had cardiac arrests); and estimates of conditional power indicated that it was highly unlikely (less than 8 percent chance) that a survival benefit from moricizine could be observed if the trial were completed. At the completion of the long-term phase, there were 49 deaths or cardiac arrests due to arrhythmias in patients assigned to moricizine, and 42 in patients assigned to placebo (adjusted P = 0.40). CONCLUSIONS. As with the antiarrhythmic agents used in CAST-I (flecainide and encainide), the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful

OBJECTIVE: To determine the effect of age on the response to anti-arrhythmic drugs. DESIGN: Randomized controlled trial comparing particular drugs. SETTING: Multi-institutional (The Cardiac Arrhythmia Suppression Trial, CAST). PARTICIPANTS: 2,371 patients, age less than 80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as less than or equal to 55, 56-65, and 66-79 years. INTERVENTION: Upwardly titrated doses of encainide, flecainide or moricizine. After identification of a tolerated and effective dose of one of the drugs, participants were randomized to that drug and dose versus its placebo for up to 10 months. MAIN OUTCOME MEASURES: Efficacy of drug (suppression of ventricular premature depolarizations and/or non-sustained ventricular tachycardia), side effects and mortality. RESULTS: Older patients had more previous MIs, congestive heart failure (CHF), hypertension, NSVT, repolarization abnormalities, digitalis use, and diuretic use. They had less pathologic Q-waves or electrocardiographic injury pattern, and their left ventricular ejection fraction (LVEF) was lower. First dose VPD suppression with the first drug averaged 53% and is not associated with age (P = 0.29). Adverse events including death are more frequent in older patients taking study drugs (P less than 0.001). This trend is consistent in all three study drugs and at varying LVEFs. History of prior MI, low LVEF, VPD (in log scale), and digitalis therapy also correlates with adverse events (all P less than 0.05). Following adjustment for these factors, older age is an independent predictor of adverse events (relative risk 1.30 per decade of age, P less than 0.001). CONCLUSIONS: Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents

The CAST was a randomized, double-blind placebo-controlled multicentre trial of antiarrhythmic medications designed to suppress ventricular arrhythmias in patients after an acute myocardial infarction (MI). A collection of 21 items derived from established scales was used to assess aspects of quality of life in CAST. The questions focused on symptoms, mental health, physical functioning, social functioning, life satisfaction, and life expectancy. Additional aspects included exposure to major stressful life events, and perceived social support and social integration. Work status was also recorded. Using the baseline values of 1465 (98%) out of 1498 patients enrolled in the CAST main study between 15 June 1987 and 19 April 1989, the reliability and validity of the scales used in CAST were computed. High internal consistency reliability (> or = 0.70) was found for Symptoms, Mental Health, and Physical Functioning. The discriminative validity, in particular for Symptoms, Mental Health, Physical and Social Functioning, showed that patients with heart failure and previous MI, as well as those suffering from angina and dyspnea, had a worse quality of life than those patients who were not experiencing these symptoms. It was concluded that the scales selected to form the CAST quality of life questionnaire were both reliable and clinically valid for this patient population and therefore could be used to detect disease progression and treatment effects

This report examines whether in the Cardiac Arrhythmia Suppression Trial death and cardiac arrest from encainide, flecainide and moricizine during the titration phase and from encainide and flecainide during the follow-up phase were related to presence (Q-wave acute myocardial infarction [Q-AMI]) or absence (non-Q-AMI) of pathologic Q waves. In all, 2,371 patients (70% with Q-AMI, 26% with non-Q-AMI, and 4% unknown) entered the titration phase, starting 117 +/- 163 days after index AMI and lasting for an average of 21 days. For the titration phase, no significant differences existed between Q-AMI and non-Q-AMI patients for death and cardiac arrest rate, ventricular premature complex suppression rate, and nonrandomization rate. A total of 1,498 patients entered the follow-up phase of an average of 10 months (starting 129 +/- 158 days after the index AMI), and were randomized to encainide or flecainide, or their matching placebos. In the placebo group, non-Q-AMI patients had a significantly lower rate of death and cardiac arrest than Q-AMI patients (1.0 and 4.6%, respectively; p = 0.04). Encainide and flecainide significantly elevated death and cardiac arrest rate in both non-Q-AMI patients (8.7%, p less than 0.01) and Q-AMI patients (7.8%, p = 0.04). The relative risk for encainide or flecainide over placebo in the non-Q-AMI patients was 8.7, which was significantly higher than 1.7 observed for the Q-AMI patients (p = 0.03). None of the baseline characteristics had any significant interaction with encainide or flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.

The prevalence, characteristics and significance of ventricular arrhythmias detected by ambulatory electrocardiography were evaluated in 1,498 patients who were randomized to encainide, flecainide or placebo in the Cardiac Arrhythmia Suppression Trial. The mean ventricular premature complex (VPC) frequency at baseline was 133 +/- 257 VPCs/hour. Nonsustained ventricular tachycardia (VT) (rate greater than or equal to 120 beats/min) was present in 22% of patients. Accelerated idioventricular rhythm (rate less than 120 beats/min) occurred in 22% of subjects. There were 63 deaths/resuscitated cardiac arrests in the active treatment (encainide/flecainide) group and 26 in the placebo group. In the treatment group mortality increased with increasing VPC frequency, (p = 0.006), whereas in the placebo group such a relation was not present. Mortality/resuscitated cardiac arrest increased in patients with greater than or equal to 2 VT episodes than in those with less than or equal to 1 episode in the active treatment group (p = 0.04). There was no significant association between VT and mortality/resuscitated cardiac arrest in the placebo group. The presence of accelerated idioventricular rhythm was not associated with increased mortality/resuscitated cardiac arrest in either the active treatment or placebo groups. However, mortality was lower in patients with accelerated idioventricular rhythm rates less than 100 beats/min than in those with rates greater than or equal to 100 beats/min (p = 0.05). Thus, in the Cardiac Arrhythmia Suppression Trial the previously described association between mortality/resuscitated cardiac arrest and ventricular arrhythmias (VPC and VT) were only observed in the active treatment group. In addition, based on the results obtained in this highly selected population, it is suggested that the definition of accelerated idioventricular rhythm should be a rate less than 100 beats/min, and at a rate greater than or equal to 100 beats/min it should be categorized as VT