Donald W. Romhilt

Events in the cardiac arrhythmia suppression trial (CAST): Mortality in the entire population enrolled

To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the natural mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Timing, mechanism and clinical setting of witnessed deaths in postmyocardial infarction patients.

The temporal distribution and mechanism of death were studied in a large multicenter secondary prevention trial (Aspirin Myocardial Infarction Study) in which acute witnessed death represented 72% (270 of 376) of the deaths due to arteriosclerotic heart disease. Instantaneous deaths represented 28.9% (78 of 270) of the acute witnessed deaths; 45.2% (122 of 270) occurred in the first hour after the onset of symptoms and were defined as sudden deaths. In the subsequent 23 hours, an additional 113 deaths (41.8%) occurred and were defined as intermediate deaths; 29 late deaths (10.7%) occurred after 24 hours. Cardiac arrhythmia was the mechanism of death in 83% (194 of 235) of deaths within 24 hours. Univariate analysis of baseline clinical and electrocardiographic characteristics indicates that a history of congestive heart failure, cardiomegaly, angina pectoris, multiple myocardial infarctions and therapy with digitalis and nitroglycerin were more common in those who died than in survivors, regardless of the timing of death.

Cesium-129 Myocardial Scintigraphy to Detect Myocardial Infarction

Cesium-129 is concentrated in the myocardium after intravenous administration permitting myocardial imaging. The dosage used was 2-2.5 mCi in dogs and 3-4 mCi in patients. Four or more views with 200,000 counts per view were obtained 30 to 90 minutes after administration. Control images were obtained in 30 dogs. In two dogs anatomic landmarks were obtained using technetium-99m markers. In 24 dogs, either the anterior descending or circumflex coronary artery was ligated. An area of absent uptake of 129Cs was seen involving the anterior wall and apex or the inferior-posterior wall, respectively. At postmortem this represented a myocardial infarction (MI) averaging 4×5 cm. Smaller MI (2×3 cm) at postmortem were seen as defects of the anterior wall. Evolution of an acute MI was followed in four dogs. The defect appeared at one hour and gradually increased on serial images. Fifty patients were studied. Each of 20 patients without evidence of MI had the normal horseshoe or doughnut appearance of the left ventricle surrounding the interventricular cavity. Each of 15 patients with acute MI and 10 of the 13 patients with an old MI had a defect on the myocardial image. The three patients without defects had infarction of the inferior wall. One of two patients with coronary insufficiency had a defect. These studies show that good quality myocardial images were obtained with 129Cs and strongly suggest its potential usefulness in quantification of an acute MI.

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and 129Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of 129Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia. Six dogs were given 129Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given 129Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of 129Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.