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 < .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 < .0001). This reduction was most pronounced in high-risk patients. Circulation 73, No. 6, 1254-1263, 1986. SUDDEN CARDIAC DEATH is a major health problem, with approximately 400,000 deaths per year in the United States." 2 Information on the clinical setting and mechanism has been obtained from autopsy series, coronary care units, and patients resuscitated after outof-hospital arrest.31-6 Patients at increased risk can be identified by clinical features and angiographic findings.5 1-21 Although ventricular arrhythmias are the usual mechanism,'6 22, 23 the initiating events remain unknown.2F In some patients, the arrhythmia may result from ischemia. If ischemia is important, coronary artery bypass grafting (CABG) could potentially play an important role and may reduce the incidence of sudden cardiac death. Previous studies on the role of CABG for prevention of sudden cardiac death have suggested a benefit from From the Mayo Clinic and Mayo Foundation, Rochester, MN. Address for correspondence: David R. Holmes, Jr.. M.D., Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Received July 30, 1985; revision accepted Feb. 27, 1986. *Contributing investigators and clinical sites are listed before the references. operation but have been limited by small sample size, variable patient selection, or the retrospective nature of the study.23 27,26 The Coronary Artery Surgery Study (CASS) circumvents some of these problems by virtue of the study design, sample size, and prospective entry and follow-up. This study analyzes the CASS registry, characterizes patients at increased risk for sudden cardiac death, and compares the impact of medical therapy alone with that of CABG on the incidence of sudden cardiac death in patients with coronary artery disease (CAD). Materials and methods Details of the CASS study, including methods, definition of terms, quality control, and baseline data, have been described.7 From 1975 to 1979, 20,270 patients without prior CABG who were undergoing coronary angiography for evaluation of suspected CAD were enrolled and prospectively studied. Except for 780 patients enrolled at 1 1 CASS randomizing centers, most of the patients (19,490) received medical or surgical treatment on the basis of patient and physician judgment. This analysis of observational data deals with the CASS registry and is not confined to randomized patients. Biases associated with unknown variables could not be evaluated. CIRCULATION 1254 by gest on Jauary 5, 2018 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-cORONARY ARTERY DISEASE The vital status as of December 1982 was known for 98% of the initially enrolled 20,270 patients: 98.1% of medically and 98.9% of surgically treated patients. The purpose of this study was to evaluate the effect of medical and surgical therapy on sudden cardiac death. We did not analyze the effect of medical and surgical therapy on all causes of death; this is the topic of forthcoming studies. The analysis is restricted to patients with significant CAD and operable vessels but no significant valvular heart disease at the time of initial angiography. Definitions Sudden cardiac death. Sudden cardiac death is defined as the sudden occurrence of death within 1 hr after the onset of symptoms and generally before the availability of medical attention. The circumstances under which death occurred were specified whenever possible. Sudden deaths were classified as occurring at home, at work, during recreational activity, in the hospital, or en route to the hospital. Sudden deaths were further classified as witnessed or unwitnessed. The definition of unwitnessed sudden cardiac death is difficult. A subcommittee of the steering committee of CASS reviewed all deaths of the randomized patients and categorized them as sudden death, nonsudden cardiac death, and noncardiac death. Unwitnessed sudden cardiac death was thought to have occurred when the patient was alive and well when last seen and soon after was discovered to be dead (for example, during sleep). In this study, 23 patients died suddenly within 30 days after cardiac operation; their deaths were considered cases of perioperative mortality and not sudden deaths. Coronary artery disease. Significant CAD was defined as 70% or more luminal diameter narrowing of the right coronary artery or of the left anterior descending or circumflex coronary arteries or their major branches or as 50% or more stenosis of the left main coronary artery. In a patient with a dominant right or balanced coronary artery system, significant stenosis of the left main coronary artery was coded as two-vessel disease; in a patient with a dominant left coronary artery, significant stenosis of the left main coronary artery was coded as three-vessel disease. Operable vessel. The term "operable vessel" is a measure of anatomic suitability for CABG. In a patient with significant CAD, an operable vessel is one with 50% or more stenosis but a normal-sized distal vessel. Left ventricularfunction. Left ventricular function was quantitated by use of monoplane left ventricular angiography. Ejection fraction was calculated by the area-length method.30 The left ventricle was divided on the right anterior oblique projection into five segments, each of which was coded for wall motion as normal, hypokinetic, akinetic, or dyskinetic. The following scoring system was used for the left ventricle: 5, normal left ventricle; 6 to 9, mild left ventricular hypokinesis; 10 to 12, moderate left ventricular regional wall motion abnormalities; and greater than 12, severe left ventricular dysfunction.29 31 Myocardialjeopardy index.31 This index was derived to identify myocardium at risk for the development of ischemia. It is used to evaluate the importance of a specific stenosis supplying an area of myocardium. Anterior myocardial jeopardy was present when a significant stenosis of the left main coronary artery or the left anterior descending artery occurred in conjunction with "viable myocardium" (that is, normal or only hypokinetic anterior left ventricular wall segments). Inferior jeopardy was present when a significant stenosis of the proximal or mid right coronary artery (or left main coronary artery or proximal circumflex artery in a left dominant system) occurred in conjunction with normal or only hypokinetic inferior wall segments. Congestive heartfailure (CHF) score. CHF was graded from 0 (no CHF) to 4 (severe CHF). This score is a count of four items: a history of CHF, the presence of pulmonary rales at baseline, the use of digitalis, and the use of diuretics at baseline. Functional impairment due to CHF was assessed with a score ranging from 0 (no CHF) to 5 (symptoms of severe CHF). Statistical analysis. Statistical comparisons between groups were performed by use of t test analysis for continuous variables and x2 analysis for discrete variables. Differences in the rates of sudden death between medically and surgically treated patients were tested by the log-rank test on the basis of the entire followup experience.32 34 Patients who died from other causes were included in the group at risk for sudden death up to the time of death. Medically treated patients were those who did not undergo operation or those who underwent operation late in the study period. Surgically treated patients were those who had CABG during hospitalization at their enrolling institution, when 95% of patients have surgery. The number of days after enrollment within which 95% of the operations were performed was determined for each hospital (average time, 4 months). At each hospital, patients who had an operation during this period, or within 90 days if this period was less than 90 days, were excluded from the medical group. Survival time was counted from the average days to operation for the hospital where the patient was enrolled.33 (Eleven medically treated patients had sudden death within 30 days after this point; these patients were included.) Patients who died before this cutoff were excluded from the analysis. This type of analysis removes the unfair bias of early deaths attributed to medical therapy in patients who may have been assigned to undergo operation.33 Cox regression analysis of the time to sudden cardiac death was used to adjust the comparison of medically and surgically treated patients for covariates. For the medically treated patients alone, five variables were selected by stepwise analysis of the time to sudden death from a group of 36 potential covariates (table 1). These variables and the coefficients estimated by the Cox analysis were used to construct a linear index of risk. The index was used to separate patients into quartiles ranging from low to high risk (see Appendix). Medically and surgically treated patients were compared within quartiles. Both medically and surgically treated patients were included in a second stepwise Cox analysis using the same 36 covariates. The effect of operation on the time to sudden cardiac death was assessed by adding a variable for operation at the final step and testing that its coefficient was significantly different from zero. The relative risk of sudden death for patients undergoing CABG was estimated by exp (b), where b is the coefficient estimated by the Cox analysis for the therapy covariate.32