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The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

The primary purpose of this study was to determine whether treatment with isradipine would prevent an exercise-induced increase in the concentration of anuclear carcasses of endothelial cells in the blood of men with angina pectoris. Endothelial cells were prepared for microscopic counting by a method involving differential centrifugation of venous blood. The endothelial cell count of 20 men increased from 0.78 +/- (SD) 0.41 per counting chamber approximately 2 h before exercise to 1.28 +/- 0.54 three minutes after moderate angina was induced by treadmill exercise (p = 0.003). After treatment with isradipine, the endothelial cell count decreased with or without treadmill exercise. These results suggest that exercise caused an increase in the endothelial cell count of men with coronary artery disease and that isradipine caused an acute decrease and prevented the exercise-induced increase in the endothelial cell count.

Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we have done a random-order, double-blind, crossover study of the effect of the platelet-active drug sulfinpyrazone on treadmill exercise-induced angina pectoris in 30 men with coronary artery disease. The mean duration of exercise before onset of angina was 43 s longer after taking sulfinpyrazone than before and 11 s shorter after taking placebo than before. Analysis of variance for crossover design showed that the mean difference between the values obtained before and after sulfinpyrazone was significantly different (p < 0.01) from the mean difference between the values before and after placebo. Sulfinpyrazone had no effect on the mean heart rate-blood pressure product at onset of angina, change in ST segment during exercise, or preexercise platelet aggregate ratio and bleeding time. Exercise until angina occurred did not affect the platelet aggregate ratio.

Although valvular lesions are rare in acromegaly, two patients with click-murmur syndrome and one patient with aortic insufficiency secondary to myxomatous degeneration and cystic medial necrosis of the aorta have been reported. Growth hormone excess has been postulated to potentiate these connective tissue defects. Excess mucopolysaccharide deposition is stimulated by growth hormone and is characteristic of both cystic medial necrosis and myxomatous degeneration. Both lesions are found in experimental lathyrism, which is potentiated by growth hormone. We observed a patient with mitral insufficiency, acromegaly documented by growth hormone levels, myxomatous degeneration of all four cardiac valves, and cystic medial necrosis of the aorta and pulmonary artery. This case presents further evidence that excess growth hormone may potentiate the connective tissue cardiovascular lesions in acromegaly.

A randomized, double-blind clinical trial in 1266 men with unstable angina showed that 324 mg of aspirin daily for 12 weeks reduced the incidence of myocardial infarction by 51% (p = .001), and the data suggested a similar reduction in mortality. The only other therapy for unstable angina that has been studied in randomized trials of adequate size to evaluate mortality and rate of infarction is aortocoronary bypass surgery. Results with heparin therapy have been encouraging, but the studies in which this drug has been tested have been flawed. Nitrates, beta-blockers, calcium blockers, fibrinolytic therapy, and coronary angioplasty have not been adequately evaluated. Randomized trials of aortocoronary bypass surgery have not demonstrated decreased mortality or rates of myocardial infarction in patients with unstable angina. Although surgical techniques have improved since these trials were conducted, medical management has also improved. Mortality and infarct rate in patients with unstable angina are now lower than in the early 1970s. New well-controlled clinical trials are needed.

We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent--10 patients (1.6 per cent) as compared with 21 (3.3 per cent)--although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality.

In recent years, it has been recommended that "high-risk" patients receive influenza immunizations annually. During the 1976 National Influenza Immunization Program, a higher priority was given to these patients than to the general population. The present study was undertaken to compare the antibody response of high-risk patients with that of a group of individuals with no underlying disease after immunization with 0.5 ml of bivalent, split-virus vaccine containing 200 CCA units each of influenza A/New Jersey/76 and A/Victoria/75. Sera were obtained before and after immunization from 41 "healthy" volunteers and from 57 cariology, 31 hematology, 13 hemodialysis, and 16 renal transplant patients. The control, cardiology, and hemodialysis groups responded equally well to A/Victoria/75 antigen, but the hematology and renal transplant groups did not respond as well (P less than .05). Only the hematology patients responded at a significantly lower level (P less than .05) than the control group to A/New Jersey/76. The control and renal transplant groups had a significantly greater response to A/New Jersey/76 antigen than to A/Victoria/75 antigen (P less than .002). Although the same pattern was demonstrated by the other patient groups, the differences were not significant. Because hematology and renal transplant patients responded relatively poorly to influenza immunization, prophylactic administration of amantadine during influenza outbreaks should be considered in patients with renal function adequate to excrete this drug.

Bacterial endocarditis is a serious complication of valve replacement, with an overall mortality of 59%. Fever, although a constant feature of the condition, is a nonspecific finding; other manifestations may or may not be present and the diagnosis may be overlooked. Any patient with a prosthetic heart valve and bacteremia should be considered to have endocarditis and should be treated accordingly.

Increased cardiovascular morbidity and mortality among cigarette smokers may be mediated in part by enhanced platelet function. Previous data showed that cigarette smoking--induced lowering of the platelet aggregate ratio of normal individuals was prevented by taking aspirin before smoking. Our study was undertaken to determine whether similar results would occur in men with coronary artery disease and whether platelet factor 4 would be released. A random-order, double-blind crossover study comparing the effects of placebo, 0.15 gm aspirin, and 0.30 gm aspirin was done in 30 male habitual smokers with coronary artery disease. Each man took a tablet containing placebo or aspirin and then abstained from smoking for 12 hours before each of three 20-minute periods of smoking two tobacco cigarettes. Immediately before and after smoking, the platelet aggregate ratio and the concentration of platelet factor 4 in platelet-poor plasma were determined from antecubital venous blood. Twelve hours after placebo, the geometric mean concentration of platelet factor 4 was 13.6 ng/ml before and 19.7 ng/ml after smoking (P = 0.0006). The mean platelet aggregate ratio was 0.77 and 0.72, respectively (P less than 0.00001). Neither dose of aspirin affected the presmoking value of or the smoking-induced change in either variable. The data indicate that smoking stimulated platelet aggregate formation and release of the contents of platelet alpha-granules, which were unaffected by preadministration of aspirin. This contrasts with the previous study of normal habitual smokers whose ingestion of 0.32 gm aspirin prevented a smoking-induced decrease in the platelet aggregate ratio.

Using a turbidimetric technique, we determined 1.7 micrometer adenosine diphosphate--induced platelet aggregation and disaggregation at 37 degrees C in the platelet-rich plasmas of two groups of men with coronary artery disease. Eleven men were nondiabetic and 11 had adult-onset diabetes mellitus without retinopathy. There were no significant differences (P greater than .05) between diabetics and nondiabetics of the following variables: age, platelet count in platelet-rich plasma, first and second phases of platelet aggregation, maximum extent of aggregation, and percent disaggregation at three minutes after maximum aggregation occurred. Although the mean adenosine diphosphate--induced platelet aggregation in the platelet-rich plasmas of adult-onset diabetic men with coronary artery disease and no retinopathy was not enhanced, and the mean rate of disaggregation was not reduced, when compared with nondiabetic men with coronary artery disease or with healthy men; a slow rate of platelet disaggregation (less than 10%) occurred more frequently in the platelet-rich plasmas of men with coronary artery disease.

Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we did a random-order, double-blind, crossover study of the effect of the platelet aggregation inhibitor, aspirin, on treadmill exercise-induced angina in 13 men with coronary artery disease. Although collagen-induced platelet aggregation and the second phase of adenosine diphosphate (ADP)-induced platelet aggregation were significantly decreased and the rate of disaggregation of ADP-induced platelet aggregates was significantly increased after 650 mg aspirin in buffered solution, there was no delay in onset of exercise-induced angina, change in heart rate-blood pressure product at onset of angina, or change in S-T segment depression at onset of angina. Regardless of whether the patients had received placebo or aspirin on the preceding day, treadmill exercise until angina was followed by no changes in platelet aggregation or disaggregation, platelet count in blood or platelet-rich plasma, or of the plasma concentration of nonesterified fatty acids.

Two large placebo-controlled, randomized, double-blind clinical trials have demonstrated the benefit of aspirin therapy in preventing myocardial infarction and death in patients with unstable angina. The Veterans Administration Cooperative Study of 1266 men hospitalized with unstable angina showed that 324 mg of aspirin daily for 12 weeks reduced the incidence of myocardial infarction by 51% (p = 0.001), and the data suggested a similar reduction in mortality. The Canadian McMaster University multicenter trial of 555 patients showed that treatment with 1300 mg of aspirin per day for a mean of 18 months reduced the incidence of cardiac death and nonfatal myocardial infarction together by 51% (p = 0.008). The reduction in death alone was 71% (p = 0.004). In the Canadian study there was no observed benefit of sulfinpyrazone. The Canadian trial confirmed the results of the VA Cooperative Study and showed statistical significance for reduction by aspirin of death as well as of myocardial infarction. It showed similar benefits in women as in men with unstable angina. The life-table curves for aspirin-treated and control patients continued to separate throughout the 2-year study period, demonstrating the value of continued treatment. The VA study showed no evidence of gastrointestinal side effects from 324 mg of aspirin daily administered in a buffered solution. Heparin therapy for unstable angina has appeared promising, but no properly conducted randomized trial has been accomplished.(ABSTRACT TRUNCATED AT 250 WORDS)