Risk of developing an acute myocardial infarction or sudden coronary death in patients with exercise-induced silent myocardial ischemia. A report from the Coronary Artery Surgery Study (CASS) registry

To evaluate whether patients with silent myocardial ischemia during exercise testing are at increased risk for developing a subsequent acute myocardial infarction or sudden death, the data on 424 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. These patients (group 1) were compared with 456 other patients with CAD (group 2) who had both ischemic ST depression and angina pectoris during exercise testing and with 1,019 control patients without CAD. The probability of remaining free of a subsequent acute myocardial infarction or sudden death at 7 years was 80 and 91%, respectively, for group 1, 82 and 93%, respectively, for group 2 (difference not significant, compared with group 1), and 98 and 99%, respectively, for the control patients (p less than 0.001), compared with group 1 or 2). Among patients in group 1, the probability of remaining free of myocardial infarction and sudden death at 7 years was related to the severity of CAD and presence of left ventricular (LV) dysfunction, and ranged from 90% for patients with 1-vessel CAD and preserved LV function to 38% for patients with 3-vessel CAD and abnormal LV function (p less than 0.001). Thus, patients with either silent or symptomatic ischemia during exercise testing have a similar risk of developing an acute myocardial infarction or sudden death--except in the 3-vessel CAD subgroup, where the risk is greater in silent ischemia. The risk of patients with silent myocardial ischemia is based primarily on angiographic variables.     

The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study

The effect of medical and surgical treatment on subsequent sudden cardiac death was assessed in 13,476 patients in the Coronary Artery Surgery Study registry who had significant coronary artery disease, operable vessels, and no significant valvular disease. (Patients were assigned to medical or surgical therapy on the basis of clinical judgment and not according to a randomization scheme; therefore, biases associated with unknown variables could not be evaluated.) Sudden cardiac death occurred in 452 patients (3.4%) during a mean follow-up of 4.6 years. Five year survival free of sudden death for medically treated patients was 94 +/- 0.3%, and that for surgically treated patients was 98 +/- 0.2% (p less than .0001). Twelve baseline clinical, electrocardiographic, and angiographic variables were significantly different between patients alive at the last follow-up and those suffering sudden death. Data on these variables were available for 11,508 patients. Sudden death occurred in 257 (4.9%) of 5258 medically treated and 101 (1.6%) of 6250 surgically treated patients. In a high-risk patient subset with three-vessel disease and history of congestive heart failure, 91% of surgically treated patients had not suffered sudden death compared with 69% of medically treated patients. After Cox survival analysis was used to correct for baseline variables, surgical treatment had an independent effect on sudden death (p less than .0001). This reduction was most pronounced in high-risk patients.     

Significance of silent myocardial ischemia during exercise testing in patients with diabetes mellitus: a report from the Coronary Artery Surgery Study (CASS) Registry

To evaluate the significance of ischemic ST depression without anginal chest pain during exercise testing among patients with diabetes mellitus, the data on 45 such patients from the Coronary Artery Surgery Study registry were analyzed. These patients (group 1, silent ischemia) were compared with 37 diabetic patients with both ischemic ST depression and chest pain (group 2, symptomatic ischemia), with 31 diabetic patients without ischemic ST depression or chest pain (group 3, no ischemia), and with 429 patients without diabetes who had silent ischemia during exercise testing. All patients had documented coronary artery disease (CAD) (greater than 70% diameter narrowing). The 6-year survival among patients with silent ischemia was worse in diabetic than nondiabetic patients (59 vs 82%, respectively, p less than 0.001). By contrast, the 6-year survival among patients without ischemia was similar among diabetic and nondiabetic patients (93 vs 85%, respectively, p = 0.476). Among diabetic patients, survival at 6 years with medical treatment was 59% for group 1, 66% for group 2 and 93% for group 3 (p = 0.008). Survival among subsets of patients with diabetes and silent ischemia (group 1) based on the extent of CAD and left ventricular function ranged from 100 to 32% (p = 0.093). The survival of the 45 patients with diabetes mellitus and silent ischemia (group 1) treated medically was compared with that of 28 patients receiving coronary artery graft bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Features of cardiac arrest episodes with and without acute myocardial infarction in the Coronary Artery Surgery Study (CASS)

Angiographic evidence of coronary artery disease was present in 16,002 patients in the Coronary Artery Surgery Study (CASS) registry. Of these patients, 551 had a history of cardiac arrest before enrollment angiography. Cardiac arrest was a complication of acute myocardial infarction (AMI) in 372 patients (68%). Electrocardiographic documentation of the responsible rhythm was available in 283 patients. Ventricular fibrillation (VF) was present in 112 (60%), ventricular tachycardia (VT) in 41 (22%) and both VT and VF in 26 (14%) patients. Stepwise linear discriminant analysis comparing the 551 cardiac arrest patients with the other 15,451 patients selected left ventricular wall motion score (F = 265), use of digitalis (F = 71), impaired blood supply to any segment (F = 16) and particularly to the anterior wall (F = 11) as discriminating variables associated with cardiac arrest. Patients with cardiac arrest occurring as a complication of AMI were younger (F = 12), had greater impairment of coronary blood supply (F = 7) and were more likely to be on a cholesterol-lowering diet (F = 16) than were patients with arrest remote from infarction. Comparison of patients with VT versus those with VF showed a positive association of VT with age (F = 8), a trend toward worse left ventricular function and presence of a left ventricular aneurysm, but no difference in severity and collateralization of coronary artery disease. It is concluded that cardiac arrest is related to the extent of myocardial damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients

The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.     

Comparison of coronary artery bypass surgery and medical therapy in patients with exercised-induced silent myocardial ischemia: a report from the Coronary Artery Surgery Study (CASS) registry

To determine whether coronary artery bypass surgery would prolong survival in patients with silent myocardial ischemia during exercise testing, the data on 692 such patients from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients were followed up for up to 7 years after medical (n = 424) or surgical (n = 268) therapy. Stratification of patients into subsets was based on the results of cardiac catheterization. Surgical benefit was greatest in the patients with three vessel coronary artery disease or abnormal left ventricular function. Among the 75 patients with three vessel coronary disease and left ventricular dysfunction, the 7 year survival rate was 37% for the medical group and 90% for the surgical group (p less than 0.0001). Thus, among patients with silent myocardial ischemia during exercise testing in this nonrandomized study, survival appeared to be enhanced by coronary artery bypass surgery in subsets of patients with severe coronary artery disease and abnormal left ventricular function.     

Prognostic significance of angiographically documented left ventricular aneurysm from the Coronary Artery Surgery Study (CASS)

In order to evaluate the prognosis of medically treated patients with angiographically defined left ventricular aneurysm the data available from 1,136 patients with aneurysm (7.6 percent) from 15,019 patients with coronary artery disease in the Coronary Artery Surgery Study (CASS) registry were analyzed. Prior myocardial infarction, reduced ejection fraction, absence of angina and evidence of congestive heart failure were more commonly present in patients with aneurysm. The cumulative survival rates of medically treated patients at 1, 2, 3 and 4 years were 90, 84, 79 and 71 percent, respectively. The Cox analysis of survival indicated that the following variables predicted outcome: age, residual left ventricular function as assessed with angiography, left ventricular end-diastolic pressure, functional impairment due to congestive heart failure, number of vessels diseased, mitral regurgitation and S₃ gallop. When survival was stratified for similar degrees of left ventricular dysfunction and functional impairment there was no difference between the survival of patients with aneurysm and that of registry patients without aneurysm.The data from this large population study indicate that the survival of patients with left ventricular aneurysm is better than previously recognized. The mortality in this group is primarily related to age, left ventricular function and clinical severity of heart failure. The presence of an aneurysm does not independently alter survival.     

Complications of coronary arteriography from the Collaborative Study of Coronary Artery Surgery (CASS).

Data were collected prospectively on 7553 consecutive patients undergoing coronary arteriography. The studies were performed at 13 clinics of the Collaborative Study of Coronary Artery Surgery (CASS) using brachial and femoral techniques. There were eight deaths 0--24 hours and seven deaths 24--48 hours after arteriography (2/1000). There were 15 non-fatal myocardial infarctions (MIs) 0--24 hours and four MIs 24--48 hours after arteriography (2.5/1000). Of 657 cases with left main stenosis greater than or equal to 50%, five died and three had MI. Left main disease increased risk of death by 6.8 times (p less than 0.001). Other factors increasing risk were unstable angina, congestive heart failure, multiple premature ventricular contractions, and hypertension. Of the 1187 patients studied from the brachial artery, six died (0.51%) and five had MIs (0.42%). In 6328 patients studied from the femoral artery, nine died (0.14%) and 14 had MIs (0.22%). The brachial artery technique increased the risk of death 3.6 times compared with the femoral approach (p less than 0.05). This result did not apply when analysis was restricted to laboratories with 80% or more brachial procedures. Risk was not altered by heparin. Thus, a prospective, multicenter analysis of complications reveals low risk of coronary arteriography but significant difference between two techniques.     

Survival of black persons compared with white persons in the Coronary Artery Surgery Study (CASS)

From July 1974 to May 1979, 573 black persons in the Coronary Artery Surgery Study (CASS) underwent coronary angiography. Compared with 23,008 white persons, larger percentages of black men and women were current smokers and reported a history of systemic hypertension. Despite the presence of chest pain, larger percentages of blacks had normal coronary arteries by angiography than did whites. The 5-year age- and sex-adjusted survival rate was 88% for whites and 82% for blacks (p less than 0.0001). Cox analysis indicated that black race was related to poorer survival in the medical group (p = 0.0006) but not in the surgical group (p = 0.28). For blacks, surgical therapy was related to a better survival rate (p = 0.009). These results raise questions concerning the effects of excess cigarette smoking and systemic hypertension and the role of coronary artery bypass surgery on survival of black persons.     

The role of exercise-induced silent myocardial ischemia in patients with abnormal left ventricular function. A report from the Coronary Artery Surgery Study (CASS) registry

To evaluate the significance of ischemic ST depression without anginal chest pain (silent ischemia) during exercise testing among patients with abnormal left ventricular function, the data on 121 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients with silent ischemia (group 1) were compared to: 124 CAD patients with both ST depression and angina (symptomatic ischemia, group 2); 159 CAD patients with neither ST depression nor angina (no ischemia, group 3); and 37 patients without CAD (controls). Survival at 7 years with medical therapy was similar for groups 1 (55%) and 2 (60%), but was substantially better for group 3 (73%, p = 0.001). Among group 1 patients with silent ischemia, survival was related to the severity of CAD (p = 0.001). Patients with silent ischemia and three-vessel CAD had a poor 7-year survival rate (37%) when treated medically. A comparable but non-randomized group of patients with silent ischemia and three-vessel CAD who underwent coronary artery bypass surgery had a much better 7-year survival rate (83%, p less than 0.0001). These results suggest that among patients with CAD and abnormal left ventricular function, silent ischemia adversely affects survival and can identify a higher risk subset of patients whose survival might be improved after coronary bypass surgery.     

Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population

The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients.     

CASS in retrospect: lessons from the randomized cohort and registry. Coronary Artery Surgery Study

The Coronary Artery Surgery Study (CASS) was a prospective, randomized evaluation of the value of coronary artery bypass grafting compared with medical therapy for stable, mildly symptomatic coronary artery disease. Also, the CASS registry collected clinic information and follow-up data from 24,959 nonconsecutive patients undergoing cardiac catheterization from 1974 to 1979. CASS has had a major impact on current management of the coronary disease patient and represents an important contribution to the cardiovascular knowledge base. Despite the large size and valuable contributions of CASS, its findings have been widely misinterpreted, especially regarding indications for coronary artery bypass surgery. This review examines CASS from the viewpoint of its methodology and some of its many published reports. A full understanding of CASS is requisite to avoid clinical misapplication of the findings of this study.     

Asymptomatic left main coronary artery disease in the Coronary Artery Surgery Study (CASS) registry

Left main coronary artery disease (i.e., greater than or equal to 50% stenosis) was found in 1,477 of 20,137 patients in the Coronary Artery Surgery Study (CAS) registry. Of these patients, 53 (3.6%) were asymptomatic. Asymptomatic and symptomatic patients were similar in regard to 1) severity of left main coronary artery stenosis (67% vs. 70%), 2) extent of proximal coronary artery disease (no differences in number of or severity of proximal stenoses), 3) left ventricular end-diastolic pressure (13 mm Hg vs. 14 mm Hg), 4) left ventricular wall motion score 9.1 vs. 8.7), and 5) number of coronary artery segments with greater than 70% stenosis (4.4 vs. 4.8). Among the asymptomatic patients, 47% received medical and 49% received surgical treatment. In the symptomatic group, 20% received medical and 78% received surgical therapy. The survival rate 5 years after surgery for treatment of left main coronary artery stenosis was 84% for the symptomatic patients and 88% for the asymptomatic patients (p = NS). Medical management of left main coronary artery disease produced a 5-year survival rate of 57% for asymptomatic patients and 58% for symptomatic patients. Within the asymptomatic subgroup, 88% of those surgically treated survived 5 years, whereas only 57% of those medically treated survived 5 years (p = 0.02). Thus, for CASS patients with left main coronary artery disease, the percentage of those that were asymptomatic is low (3.6%); asymptomatic and symptomatic patients with left main coronary artery disease had no significant difference in severity of left main coronary artery stenosis, extent of overall coronary artery disease, or left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total occlusion of the left main coronary artery: The Coronary Artery Surgery Study (CASS) experience

Total occlusion of the left main coronary artery was confirmed on review of the coronary angiograms in 12 (0.06 percent) of the 20,197 patients entered into the Coronary Artery Surgery Study (CASS) before coronary arterial surgery. Clinical features alone could not distinguish the patients with total occlusion of the left main coronary artery from those enrolled in the CASS with subtotal stenosis of this vessel. The right coronary artery had a stenosis greater than or equal to 70 percent of luminal diameter in 7 of the 12 patients. Collateral flow to the left coronary artery was defined as “substantial” or “limited” based on the presence or absence of clear visualization of the main channel of either the left anterior descending or left circumflex coronary artery during coronary angiography. Of the eight patients with “substantial” collateral flow, one (13 percent) had an aneurysmal or dyskinetic left ventricular wall segment, whereas all (100 percent) of the three patients with “limited” collateral flow had dyskinesia or an aneurysm (p < 0.05). Seven patients underwent coronary bypass graft surgery; 6 (86 percent) of these patients were living at their most recent follow-up, a mean of 46 months after entry into the CASS. Two of these patients continued to have angina pectoris. Five patients did not undergo coronary bypass grafting and 2 (40 percent) were still alive at their most recent follow-up, a mean of 45 months after entry into the CASS. One of these patients had angina pectoris. The difference in survival between the medical and surgical groups was not statistically significant.

This study indicates that patients with total occlusion of the left main coronary artery are uncommon and cannot be distinguished by presenting features alone from patients having subtotal stenosis of the left main coronary artery. “Substantial” coronary collateral blood flow is associated with better left ventricular wall motion than is “limited” collateral flow. Prolonged survival and lessening of symptoms may occur after coronary bypass grafting although long-term survival is possible without it.     

Age variation in the association between angiographic coronary disease and angina from the Coronary Artery Surgery Study (CASS)

Between July 1974 and May 1979, 19,153 non-randomized patients without prior cardiac surgery and with chest pain were studied angiographically and enrolled in the Coronary Artery Surgery Study (CASS). The primary question addressed by this paper is: for fixed levels of coronary artery disease, are the presence and severity of angina pectoris greater for older than for younger patients? For those with the same extent of disease, older patients were more likely to have angina and to exhibit more severe symptoms. After adjustment for covariates using logistic regression analysis, age was found to be an important, independent predictor of the presence and severity of angina. There are many possible explanations for these findings, although physiologic factors related to aging, the disease process, and deconditioning associated with an increased sedentary life style seem most reasonable. Another possibility has to do with referral patterns for study and the prevalence of angina in the different age groups.     

Ten-year outcome after coronary angioplasty in patients with single-vessel coronary artery disease and comparison with the results of the Coronary Artery Surgery Study (CASS)

The 10-year results of randomized trials comparing percutaneous transluminal coronary angioplasty (PTCA) in patients with single-vessel coronary artery disease (CAD) with coronary artery bypass grafting (CABG) and medical treatment are not available yet. The aim of this evaluation was to compare our 10-year follow-up results after PTCA in patients with single-vessel CAD with the 10-year follow-up results after CABG and medical treatment in the Coronary Artery Surgery Study (CASS) trial. We evaluated the clinical outcome of 509 patients with single-vessel CAD 10 years after coronary angioplasty. The data were compared with the results of 214 patients with single-vessel CAD after CABG or medical treatment from the CASS trial. End points were defined as death and myocardial infarction. Statistical evaluation was performed by life-table analysis and 2-sided Fisher's exact test. The rate of survival was 86% 10 years after PTCA compared with 85% after CABG and 82% after medical treatment in patients from the CASS trial (p = NS). Survival free from myocardial infarction was 77% after coronary angioplasty, 70% after CABG, and 72% after medical treatment (p = NS). Thus, in patients with single-vessel CAD, infarct-free survival 10 years after coronary angioplasty compared favorably with the results after bypass surgery or medical treatment from the CASS trial.     

Comparison of the long-term, postsurgical survival of women and men in the Coronary Artery Surgery Study (CASS)

This study compares the survival of men and women an average of 6 years after coronary artery bypass graft surgery (CABG) by means of the Coronary Artery Surgery Study (CASS) registry. Subjects included in these analyses were the 6100 men and 1097 women who survived surgery. Medical history and physical and laboratory information were collected from each patient at baseline. Men and women were compared for differences in baseline characteristics, long-term survival (by means of the Cox proportional hazards models), and predictors of long-term survival. In this study women, at baseline, were older and more likely to have hypertension and diabetes compared to men; whereas men were more likely to have had prior coronary heart disease. In this study of CASS participants there was no difference between men and women with regard to survival after CABG. There was also no difference between men and women in predictors of 6-year mortality. Two baseline variables were strongly related to subsequent mortality in both men and women: a high left ventricular wall motion score and taking both digitalis and diuretics (for women: relative risk = 2.31, confidence interval = 1.38 to 3.87; for men: relative risk = 1.90, confidence interval = 1.45 to 2.50).     

Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry.

BACKGROUND. Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS. The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS. Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction.