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Prognostic significance of left ventricular aneurysm in the Cardiac Arrhythmia Suppression Trial (CAST) population
Hochman, J S; Brooks, M M; Morris, M; Ahmad, T; Patt, M
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
PMID: 8154420
ISSN: 0002-8703
CID: 113730
Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. CAST Investigators
Kennedy, H L; Brooks, M M; Barker, A H; Bergstrand, R; Huther, M L; Beanlands, D S; Bigger, J T; Goldstein, S; Patt, Mitchell
The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional beta-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of < or = 40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional beta-blocker therapy prescribed at baseline. CAST patients receiving beta-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed beta-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, beta-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of beta-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of beta-blocker therapy against proarrhythmic events experienced in the CAST
PMID: 7942525
ISSN: 0002-9149
CID: 97988
Sabin lessened fear while defeating Polio [Newspaper Article]
Patt, Mitchell
ORIGINAL:0006631
ISSN: n/a
CID: 101877
Methods for assessing quality of life in the cardiac arrhythmia suppression trial (CAST)
Willund, I; Gorkin, L; Pawitan, Y; Schron, E; Schoenberger, J; Jared, L L; Shumaker, S; Patt MV; CAST investigators
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
PMID: 1301128
ISSN: 0962-9343
CID: 92586
Effects of advancing age on the efficacy and side effects of antiarrhythmic drugs in post-myocardial infarction patients with ventricular arrhythmias. The CAST Investigators
Akiyama, T; Pawitan, Y; Campbell, W B; Papa, L; Barker, A H; Rubbert, P; Friedman, L; Keller, M; Josephson, R A; Patt, Mitchell
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
PMID: 1607582
ISSN: 0002-8614
CID: 97991
The cardiac arrhythmia suppression trial [Letter]
Buss, J; Lasserre, J J; Heene, D L; Patt, M
PMID: 1359413
ISSN: 0028-4793
CID: 97790
Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators
Patt MV; et al
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
PMID: 1377359
ISSN: 0028-4793
CID: 84008
DISSOCIATION OF LETHAL AND NONLETHAL EVENTS IN THE CARDIAC ARRHYTHMIA SUPPRESSION TRIAL CAST [Meeting Abstract]
ECHT D S; LIEBSON P R; MITCHELL L B; PETERS R W; OBIAS-MANNO D; BARKER A H; ARENSBERG D; BAKER A; FRIEDMAN L; PATT M; ET AL
BIOSIS:PREV199140113388
ISSN: 0735-1097
CID: 169044
Events in the cardiac arrhythmia suppression trial: baseline predictors of mortality in placebo-treated patients
Capone, R J; Pawitan, Y; el-Sherif, N; Geraci, T S; Handshaw, K; Morganroth, J; Schlant, R C; Waldo, A L; Patt, Mitchell
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.
PMID: 1939943
ISSN: 0735-1097
CID: 169043
Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-Q-wave acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial. CAST Investigators
Akiyama, T; Pawitan, Y; Greenberg, H; Kuo, C S; Reynolds-Haertle, R A; Patt, Mitchell
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)
PMID: 1720917
ISSN: 0002-9149
CID: 97989