Increased risk of urgent revascularization

J

THoRAc CARDIOVASC SURG

1987;93:291-9

Increased risk of urgent revascularization To detennine the risk factors for operative mortality and morbidity, we performed a prospective analysis of 1,980 patients undergoing isolated coronary artery bypass operations between 1982 and 1984. The operative mortality was 3.5 %, and the incidence of perioperative myocardial infarction was 8.6 % and low output syndrome, 12.0%. Stepwise logistic regression identified sex, preoperative left ventricular ejection fraction, and the urgency of operation as independent risk factors for postoperative mortality. Urgent revascularization was performed in patients with unstable angina refractory to maximal medical therapy. In these patients the operative mortality was 8.5 %. Independent risk factors of postoperative morbidity, in addition to sex, ejection fraction, and urgent revascularization, included a previous bypass procedure, age, and New York Heart Association functional class. Unstable angina unresponsive to medical therapy contributed significantly to the operative risk. Interventions to reduce perioperative ischemic injury, such as improved methods of myocardial protection, may improve the results in high-risk patients.

Kevin H. Teoh, M.D., George T. Christakis, M.D., Richard D. Weisel, M.D., Arnon M. Katz, M.D., Cathy P. Tong, H.R.A., Lynda L. Mickleborough, M.D., Hugh E. Scully, M.D., Ronald J. Baird, M.D., and Bernard S. Goldman, M.D.,

Toronto, Ontario, Canada

Although the overall results of coronary artery bypass have improved in recent years, some patients face an increased mortality and morbidity. Identification of risk factors may permit the development of alternate methods to improve the results of the procedure. Information on 1,980 patients undergoing coronary artery bypass was collected prospectively and analyzed by univariate and multivariate techniques to identify current risk factors. Methods Patient population. A total of 1,980 patients undergoing isolated coronary artery bypass between January 1982 and December 1984 were prospectively evaluated. During this period 3,110 patients underwent cardiac operations at our institution. Coronary artery bypass was performed in combination with valvular From the Division of Cardiovascular Surgery, Toronto General Hospital, Toronto, Ontario Canada. Supported by the Heart and Stroke Foundation of Ontario and the Canadian Heart Foundation. Received for publication Jan. 27, 1986. Accepted for publication March 7, 1986. Address for reprints: Richard D. Weisel, M.D., Cardiovascular Surgery, Toronto General Hospital, 200 Elizabeth St., Eaton N. 13-224, Toronto, Ontario, Canada, M5G 2C4.

procedures in 154 patients, left ventricular aneurysm resection in 87 patients, and other procedures in 29 patients; these patients were excluded from this analysis. Clinical presentation. The following information was collected preoperatively: age, sex, New York Heart Association (NYHA) functional class, and previous bypass operations. The patients' ages were categorized into the following groups: 1 = <40 years, 2 = 40 to 49 years, 3 = 50 to 59 years, 4 = 60 to 69 years, and 5 = >70 years. The timing of the operation was designated as elective, semielective, or urgent. Patients admitted to the coronary care unit with unstable angina were entered into a management protocol, which was followed consistently during this period (Fig. 1). The protocol was intended to delay the operation if possible. Unstable angina was defined as prolonged (greater than 15 minutes) rest angina, with or without electrocardiographic (ECG) changes or cardiac enzyme elevations. Initial medical treatment in the coronary care unit consisted of the administration of beta blockers, calcium channel antagonists, and/or intravenous nitrates. Patients who had angina despite medical therapy proceeded to cardiac catheterization and urgent operation within 72 hours of catheterization. Patients who responded to medical therapy in the coronary care unit were admitted to the ward and received oral antianginal 291

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Fig. 1. Management protocol for patients with unstable angina. CCU, Coronary care unit. ACB, Aorta-coronary bypass.

medications. Patients remaining asymptomatic in the hospital were usually discharged. Some patients returned for elective coronary angiography and a bypass operation if symptoms persisted despite medical therapy. Patients continuing to have angina in the hospital despite maximal oral therapy underwent catheterization and a semielective operation during that hospitalization. During this period, 224 patients underwent urgent operation and 152 patients had semielective operations. The remaining 1,604 patients had operation on an elective basis. Of the patients undergoing urgent operation, 131 patients had acute coronary insufficiency characterized by prolonged angina with reversible ECG changes and no enzyme changes. Seventy-seven patients had persistent ECG changes and enzyme changes (less than twice normal) and were believed to have suffered a preoperative subendocardial infarction. Sixteen patients continued to have rest angina after the development of new Q waves and had enzyme elevations consistent with a diagnosis of a transmural myocardial infarction before urgent operation. Fifty-four patients required intraaortic balloon pump counterpulsation to achieve anginal relief before urgent operation, and five patients required counterpulsation for preoperative hemodynamic stabilization before urgent revascularization for persistent ischemic chest pain. Among the 152 patients who underwent semielective operation, 137 were treated for acute coronary insufficiency in the coronary care unit. Thirteen patients had a subendocardial infarction, and two patients had a transmural myocardial infarction in the coronary care unit. Catheterization data. Cardiac catheterization was performed in all patients to assess ventricular function and the extent of coronary artery disease. The left ventricular ejection fraction was estimated from a single-plane contrast ventriculogram and graded on a scale from 1 to 4 (1 = >60%, 2 = 40% to 60%, 3 = 20% to 40%, and 4 = <20%). The degree of coronary artery

Thoracic and Cardiovascular Surgery

narrowing was determined from a review of at least two views of each coronary vessel. In assessing the extent of coronary disease, the left ventricle was divided into three regions: left anterior descending, circumflex, and right coronary artery, A significant stenosis to the major artery supplying one of these regions was defined as a narrowing equal to or greater than 50% stenosis by diameter. Anesthetic management and operative technique. Similar anesthetic and surgical techniques were used by the anesthetists and five surgeons. Fentanyl citrate was used for the induction and maintenance of anesthesia. Moderate hemodilution (hematocrit 20% to 25%) and systemic hypothermia (25 to 28° C) were maintained during cardiopulmonary bypass. Multidose cold crystalloid cardioplegia was employed in the majority (1,569) of patients. Cold blood cardiopelgia was employed in 150 patients, and intermittent anoxic arrest was employed in 255 patients. Postoperative outcomes. The postoperative outcomes were operative mortality, perioperative myocardial infarction, and low output syndrome. Operative mortality was defined as a death occurring within 30 days of operation or during the hospital stay. A perioperative myocardial infarction was defined as the appearance of a new Q wave on the ECG or an elevation in creatine kinase (CK-MB) isoenzyme greater than 50 IV /L or 8% of the total CK when the ECG revealed a left bundle branch block or inadequate R wave progression. Preoperative and postoperative ECGs were reviewed by a cardiologist who was not involved in the clinical care of the patient. Low output syndrome was defined as the requirement for inotropic medications for greater than 30 minutes and/or intra-aortic balloon counterpulsation to maintain systolic blood pressure greater than 90 mm Hg. Statistical analysis. The SAS* and BMDPt statistical programs were used for statistical analysis. The predictors of operative mortality, perioperative myocardial infarction, and low output syndrome were determined by univariate and multivariate techniques. For the univariate analysis, discrete data were analyzed with chi square analysis, Fisher's exact test, and MannWhitney V tests where appropriate. Continuous data were evaluated by t tests or an analysis of variance. Statistical significance was assumed when the p value was less than 0.05. All discrete and continuous variables, which were significant by univariate analysis, were entered into the "Statistical Analysis Systems Institute Inc., Cary, N. C. tBMDP Statistical Software,Los Angeles, Calif.

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293

Table I. Patient profile Patient group

No. Age (yr) Sex (male) NYHA class 1 II III

IV Reoperation Ejection fraction >60% 40-60% 20-40% <20% Diseased vessels 1 2 3 Left main stenosis No. of bypasses I 2 3 4 5

All

Elective

Sernielective

Urgent

1,980 57.1 ±8.9 1,630 (82.3%)

1,604 56.7 ± 8.8 1,341 (83.6%)

152 57.5 ± 9.4 123 (80.9%)

224 59.5 ± 8.8 166 (74.1%)

56 330 819 775 104

( 2.8%) (16.7%) (41.4%) (39.1%) ( 5.3%)

56 325 742 581 34

( 3.5%) (20.3%) (46.3%) (29.9%) ( 2.1%)

5 51 96 3

( 3.3%) (33.5%) (63.2%) ( 2.0%)

26 (11.6%) 198 (88.4%) 18 (8.0%)

1,018 556 353 53

(51.4%) (28.1%) (17.8%) ( 2.7%)

839 451 272 42

(52.3%) (28.1%) (17.0%) ( 2.6%)

73 40 37 2

(48.0%) (26.3%) (24.4%) ( 1.3%)

106 65 44 9

(47.3%) (29.0%) (19.7%) (4.0%)

128 490 1,362 223

( 6.5%) (24.7%) (68.8%) (11.3%)

97 ( 6.1%) 392 (24.4%) 1,115 (69.5%) 158( 9.9%)

7 30 115 28

( 4.6%) (19.7%) (75.7%) (18.4%)

24 68 132 37

(10.7%) (30.3%) (59.0%) (16.5%)

103 357 896 530 99

( 5.2%) (18.0%) (45.1%) (26.7%) ( 5.0%)

6 24 78 41 3

(3.9%) (15.8%) (51.3%) (27.0%) (2.0%)

17 54 92 50 II

(7.6%) (24.1 %) (41.1%) (22.3%) (4.9%)

multivariate analysis using the stepwise logistic regression technique (see appendix) with the BMDP program. Interpretation and illustration of the logistic curves were based on the predicted probability for postoperative outcome using the variables found to be significant. Results Clinical presentation and angiographic results. The patient profile is presented in Table I. The majority of patients were male. Elective operations were performed in 81% of patients, semielective operations in 8%, and urgent operations in 11%. Second or third operations were performed in 5.3% of the patients. Eighty percent ofthe patients were in NYHA Functional Class III or IV. Catheterization data revealed that the majority (79%) of the patients had good left ventricular function, with an ejection fraction greater than 40% (Table 1). Ninety-four percent of the patients had double- or triple-vessel coronary artery disease, and 11% had significant narrowing of the left main coronary artery. The average number of bypasses performed was 3.1 ± 0.9 per patient. Patients with single-vessel disease received 1.5 ± 0.7 bypasses per patient, those with

80 278 724 438 84

( 5.0%) (17.3%) (45.1%) (27.3%) ( ).)%)

double-vessel disease received 2.6 ± 0.7, and those with triple-vessel disease received 3.4 ± 0.8 bypasses per patient. There was no difference in the extent of revascularization among patients undergoing elective (3.1 ± 0.9), semielective (3.1 ± 0.8), or urgent (2.9 ± 1.0 bypasses per patient) operations. Postoperative outcomes. The outcome of patient's operations was similar among the five surgeons. Seventy patients (3.5%) died, and 170 patients (8.6%) had a perioperative myocardial infarction. Postoperative low output syndrome occurred in 12.0% (237 patients). Other complications were infrequent and included reexploration for postoperative bleeding (2.1%), a persistent focal neurologic deficit (1.9%), or a sternal infection (2.4%). Cardiac failure was the cause of death in the majority of cases (59 patients, 84.2%). The remaining 11 patients died of other causes: postoperative stroke (seven patients, 10%), sternal wound infection (two patients, 2.9%), and pulmonary embolism (two patients, 2.9%). Patients undergoing urgent revascularization had an operative mortality of 8.5% (19 patients), an incidence of perioperative myocardial infarction of 11.2% (25 patients), and low output syndrome of 21.4% (48

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Table II. Univariate risk factors of postoperative outcome for all patients

Variable Ejection fraction <60% 40-60% 20-40% <20% NYHA class I II III IV Timing of operation Elective Semi elective Urgent Sex Male Female Age (yr) Alive Dead Reoperation No Yes Diseased vessels I

Operative mortality (%)

p Value

1.5 3.1 8.2 17.0

0.0001

0.0 1.2 2.7 5.7

Low output syndrome (%)

P Value

Myocardial infarction (%)

p Value

8.2 10.2 22.1 35.9

0.0001

0.0002

8.2 8.1 10.6 15.4

0.002

8.3 5.7 7.5 4.3

0.02

2.9 3.9 8.5

0.001

10.8 14.5 21.4

0.001

8.1 11.8 11.7

0.04

2.7 7.4

0.001

10.9 16.9

0.002

57.1 ± 8.9 59.2 ± 8.4

0.05

56.8 ± 8.9 59.6 ± 8.7

0.0001

3.4 6.7

0.D7

11.4 23.1

0.003

8.6 8.2 13.7

0.003

11.4 16.1

0.04

11.4 16.1

0.03

2 3 Left main stenosis No Yes Endarterectomy No

Yes

patients). Operative mortality in the subgroup undergoing urgent operation after acute coronary insufficiency was 6.1% compared with 9.1% for those with subendocardial infarction and 25% for patients with transmural infarction (p < 0.(01). Patients who required preoperative intra-aortic balloon pump assistance had an operative mortality of 17.0% compared with 5.4% for patients undergoing urgent operation without balloon pump assistance. The complications of the intra-aortic balloon pump did not contribute to perioperative mortality. Limb ischemia developed in three patients (5.1%) and resolved with the removal of the balloon pump. Femoral artery occlusion developed in three patients who required thrombectomy. Patients undergoing semielective operation had results similar to those of patients undergoing elective operation. Determinants of outcome. The univariate predictors of operative mortality, perioperative myocardial infarc-

7.4 8.4 11.9

0.06

IJ.3

tion, and low output syndrome are listed in Table II. The significant variables were analyzed by multivariate logistic regression, which identified the independent predictors of postoperative outcome. Operative mortality was predicted by sex (p < 0.001 improvement, chi square analysis), ejection fraction (p < 0.001), and the need for urgent operation (p = 0.001). The logisticcurve is illustrated in Fig. 2. Patients at greatest risk (49% predicted mortality) were women with an ejection fraction less than 20% undergoing an urgent operation. The lowest risk «1 % predicted mortality) was found in men with an ejection fraction greater than 60% undergoing elective operation. Blood cardioplegia was associated with a lower mortality (0.7%) than either crystalloid cardioplegia (3.8%) or intermittent anoxic arrest (3.9%), but the differences were not statistically significant (p = 0.2). Postoperative low output syndrome was independent-

Volume 93 Number 2 February 1987

Urgent revascularization

295

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Fig. 2. The risk factors for operative mortality were sex, ejection fraction, and urgent operation (by stepwise logistic regression). The risk for a woman with an ejection fraction less than 20% undergoing urgent operation is 49%. LV, Left ventricle.

ly predicted by urgent operation (p < 0.001), ejection fraction (p < 0.(01), sex (p = 0.004), reoperation (p = 0.(07), and age (p = 0.008, Fig. 3). Patients at greatest risk for low output syndrome postoperatively were women between 50 and 60 years of age with poor ventricular function (ejection fraction <20%) undergoing urgent reoperation (74% risk of low output syndrome), The lowest risk patients were young men (30 to 40 years of age) with good ventricular function (ejection fraction >60%) undergoing an elective bypass as their first procedure (2.3% risk of low output syndrome). Patients undergoing reoperation tended to have poorer ventricular function (ejection fraction <40%, 29%) than patients undergoing their first operation (20%, p = 0.09). The NYHA functional class independently predicted perioperative myocardial infarction. Urgent operation and ejection fraction were the univariate but not multivariate predictors of myocardial infarction. Urgent revascularization. Since urgent revascularization was a significant risk factor for postoperative mortality, myocardial infarction; and low output syndrome, a separate analysis was performed on the group of 224 patients who required urgent operation. The clinical,angiographic, and intraoperative characteristics of these high-risk patients were similar to the entire group (Table I). The univariate risk factors for mortality, myocardial infarction, and low output syndrome are presented in Table III. The independent risk factors of mortality for patients undergoing urgent revasculariza-

Logit Score -3.7 Sex M 1 LVGrade Urgent Surgery Redo AgeGroup

-32

F 1

-1.8 -1.4 -1.2 -0.7 F M F M 4 1 1 4 - + + - + + 1 3 4

-0.2 M

4

1.1 F 4

+ t

3

Fig. 3. Postoperative low output syndrome was independently predicted by sex, ejection fraction, age, reoperation, and urgent operation. Age group: I = < 40 years, 2 = 40 to 49 years, 3 = 50 to 59 years, 4 = 60 to 69 years.

tion are presented in Fig. 4 and included the presence of left main coronary artery disease (p = 0.002, improvement chi square) and ejection fraction (p = 0.005). The risk for a patient with left main coronary disease and poor ejection fraction «20%) was 66% compared with 2% for a patient without left main coronary stenosis and with good ventricular function (ejection fraction >60%). Reoperation independently predicted perioperative myocardial infarction (p = 0.04). The extent of coronary disease was a univariate but not multivariate risk factor (Table 11). Blood cardioplegia reduced the risk of perioperative myocardial infarction (9.1%) compared with crystalloid cardioplegia (13.8%), but the difference did not reach statistical significance (p = 0.07). Low output syndrome was predicted by ejection fraction (p = 0.(03), extent of coronary disease (p = 0.(06) and repeat operation (p = 0.(06) as depicted in Fig. 5. An ejection fraction of less than 20%, triple-vessel coronary disease and reoperation produced the highest risk of low output syndrome (90%). Discussion

In this prospective analysis of patients undergoing coronary artery bypass grafting, the independent preoperative predictors of operative outcome were sex, ejection fraction, urgent operation, reoperation, age, and functional class. Female gender has been previously reported to increase the risk of surgery.'? Fisher and associates'

The Journal of

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Teoh et al.

Thoracic and Cardiovascular Surgery

Table ill. Univariate risk factors of postoperative outcome for patients undergoing urgent revascularization for unstable angina Operative mortality Variable Ejection fraction >60 40-60% 20-40% Sex Male Female Left main stenosis

No Yes Endarterectomy

(%)

p Value

3.8 6.2 18.2

0.001

6.6 13.8

0.09

5.9 21.6

0.03

No Yes Reoperation

No Yes Diseased vessels I 2

3

postulated that small physical size and small coronary arteries rather than gender may have increased the risk of coronary artery bypass in women. Poor preoperative ejection fraction increased the surgical risk in patients undergoing elective or urgent operation. Using multivariate statistics the Coronary Artery Surgery Studies (CASS)1,2 also found ejection fraction to be predictive of operative mortality. Loop and associates' found that ventricular dysfunction and the presence of congestive heart failure increased the risk of myocardial revascularization. Hochberg and colleagues' reported an operative mortality of 37% for patients with an ejection fraction less than 20%. Age was an independent risk factor of postoperative ventricular dysfunction (low output syndrome). Miller," Kennedy," 10 and Chaitman, 1 and their associates have also identified age as an operative risk factor. Older patients had more diffuse coronary artery disease and poorer ventricular function. Brawley and colleagues" found that ventricular function and extent of coronary disease influenced the mortality of elderly (>70 years) patients undergoing revascularization for unstable angina. Reoperation did not increase the risk of perioperative mortality but was associated with an increased risk of perioperative myocardial infarction in patients undergoing urgent operation. Irarrazaval and associates? also

Low output syndrome (%)

p Value

Myocardial infarction (%)

p Value

14.2 18.5 36.4

0.003

19.3 40.9

0.02

18.9 50.0

0.002

9.7 27.8

0.02

12.5 11.8 28.0

0.02

0.0 7.4 15.2

0.05

reported an increased risk of perioperative myocardial infarction after reoperation. They attributed the increased risk to the longer duration of these operations and the presence of diffuse atherosclerosis in patients undergoing reoperation. These factors may have contributed to the increased risk of postoperative lowoutput syndrome in patients undergoing reoperation. The extent of coronary artery disease and left main stenosis were univariate predictors of morbidity in all patients and were independent predictors in patients undergoing urgent operation. Others have also reported the extent of coronary disease to be predictive of surgical outcome."!" Severe coronary obstructions may limit cardioplegic delivery and increased the potential for perioperative ischemic injury. Patients who required urgent revascularization for unstable angina resistant to maximal medical therapy faced an increased risk of operative mortality, perioperative myocardial infarction, and postoperative low output syndrome. Miller and colleagues" also found that the urgency of operation was an independent risk factor. Operative mortality was 12%, and the incidence of perioperative myocardial infarction was 8% for patients undergoing urgent operation compared with I % and 3% for those undergoing elective operation. The CASS experience':' also identified the urgency of operation as an independent predictor of outcome.

Volume 93 Number 2 February 1987

100


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Fig. 4. The independent risk factors for operative mortality in patients with unstable angina undergoing urgent revascularization were ejection fraction and the presence of left main coronary stenosis.

The causes of the increased risk of operation in patients with unstable angina are unknown but are likely due to severe and prolonged preoperative ischemia. Patients with unstable angina have a high incidence of abnormal pyrophosphate scans,12.13 resting ECG changes," and elevated cardiac enzymes preoperatively," which suggests persistent ischemia and diminished myocardial metabolic and functional reserve. In addition, patients in whom ischemic ECG changes developed during rest angina have been shown to have intermittent coronary artery oclusion" and transient reductions in regional myocardial perfusion." In this series, mortality was higher in patients who had a subendocardial or a transmural myocardial infarction preoperatively and in those requiring the intra-aortic balloon preoperatively for control of angina. This higher mortality suggests that the degree of preoperative ischemia increased the risk of perioperative ischemic injury. Since 1978 we have attempted to delay surgical revascularization to avoid operative intervention during ischemia." In this study, patients who responded to medical therapy and underwent semielective coronary bypass operation had satisfactory results similar to those patients undergoing elective operation. Huret and associates" also reported good results in 80 patients with unstable angina who were stabilized medically before saphenous vein grafting. It is possible that our attempt to delay operation in all patients with unstable angina increased the ischemic injury and contributed to the higher risks in those who failed to respond to medical treatment and required

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Logit Score -2.9 -2.5 LVGrade 1 2 Reoperation No. CAD 2 2

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urgent operation. Alternative techniques of preoperative preparation or intraoperative protection may reduce the risk in these patients. Preoperative intra-aortic balloon pump assistance may reduce preoperative ischemic injury and may restore myocardial metabolic and functional reserve before coronary revascularization." Several nonrandomized trialszo•2 1 have reported that preoperative intraaortic balloon pumping eliminated ischemic chest pain and improved results of urgent revascularization for unstable angina. The physiologic mechanisms for the relief of ischemic chest pain in patients with unstable angina remain controversial but may include a reduction in myocardial oxygen demand>" and an increase in regional collateral coronary blood flOW. 25• 26 In selected patients the risks of preoperative balloon pump assistance are minimal, and the benefits may be substantial." Patients in this study with preoperative intraaortic balloon pump assistance had poorer results, probably because they had more severe preoperative ischemic injury than patients who did not require the balloon pump for relief of ischemic pain. Their operative results may have been even worse without balloon counterpulsation. Preoperative metabolic preparation may also reduce the risks. Blood cardioplegia provided better protection than crystalloid cardioplegia for elective coronary bypass" by permitting oxidative metabolism, preserving high-

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energy phosphates, and improving postoperative function, but the clinical differences were subtle. A prospective randomized trial in patients undergoing urgent or semielective operation for unstable angina demonstrated that blood cardioplegia reduced mortality, myocardial infarction, and low output syndrome and postoperative ischemic injury (by CK-MB analysis)." The addition of calcium antagonists, 3D metabolic substrates," or the technique of warm induction" may further improve myocardial protection for these high-risk patients. Patients with unstable angina requiring urgent revascularization face an increased risk of operation. Preoperative preparation and improved myocardial protection may reduce the extent of perioperative ischemia and improve the results in these patients.

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We wish to extend our appreciation to Ms. Susan Slattery, Ms. Eslyn Kesper, and Ms. M. Mindy Madonik for preparation of the manuscript. REFERENCES

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Chaitman BR, Rogers WJ, Davis K, et at. Operative risk factors in patients with left main coronary artery disease. N Engl J Med 1980;303:953-7. Kennedy JW, Kaiser GC, Fisher LD, et al. Clinical and angiographic predictors of operative mortality from the collaborative study in coronary artery disease (CASS). Circulation 1981;63:793-802. Fisher LD, Kennedy JW, Davis KB, et at. Association of sex, physical size, and operative mortality after coronary artery bypass in the Coronary Artery Surgery Study (CASS). J THORAC CARDIOVASC SURG 1982;84:334-41. Loop FD, Berretion IN, Pichard A, et al. Selection of the candidate for myocardial revascularization. J THORAC CARDIOVASC SURG 1975;69:40-51. Hochberg MS, Parsonnet Y, Gielchinsky I, Hussain SM. Coronary artery bypass grafting in patients with ejection fractions below forty percent. Early and late results in 466 patients. J THORAC CARDIOVASC SURG 1983;86:519-27. Brawley RK, Merrie W, Gott YL, Donahoo JS, Watkins L, Gardner TJ. Unstable angina pectoris. Factors influencing operative risk. Am Surg 1980;191:745-50. Irarrazaval MJ, Cosgrove DM, Loop FD, Ennix CL Jr, Groves LK, Taylor Pc. Reoperations for myocardial revascularization. J THORAC CARDIOVASC SURG 1977; 73:181-8. Laugou RA, Wiles JC, Cohen LS. Coronary surgery for unstable angina pectoris. Incidence and mortality of perioperative myocardial infarction. Br Heart J 1978; 40:767-72. Baur HR, Peterson TA, Arnar D, Gannon PG, Gobel FL. Predictors of perioperative MI in coronary artery operation. Ann Thorac Surg 1981;31:36-44. Kennedy JW, Kaiser GC, Fisher LD, et al. Multivariate discriminant analysis of the clinical and angiographic predictors of operative mortality from the Collaborative

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Study in Coronary Artery Surgery (CASS). J THORAC CARDIOVASC SURG 1980;80:876-87. Miller DS, Stinson EB, Oyer PE, et al. Discriminant analysis of the changing views of coronary artery operations: 1971-1979. J THORAC CARDIOVASC SURG 1983; 85:197-213. Jaffe AS, Klein MS, Patel BR, Siegel BA, Roberts R. Abnormal technetium-99m pyrophosphate images in unstable angina: ischemia versus infarction? Am J Cardiol 1979;44:1035-9. Olson HG, Lyons KP, Aronow WS, Stinson PJ, Kuperus J, Waters HJ. The high-risk angina patient: identification by clinical features, hospital course, electrocardiography and technetium-99m stannous pyrophosphate scintigraphy. Circulation 1981;64:674-84. Johnson MS, Mauritson Dr, Winniford MD, et al. Continuous electrocardiographic monitoring in patients with unstable angina pectoris: identification of high-risk subgroup with severe coronary artery disease, variant angina, and/or impaired early prognosis. Am Heart J 1982;103:412. Neill WA, Wharton TP, Fluri-Lundeen J, C Cohen IS. Acute coronary insufficiency-coronary occlusion after intermediate ischemic attacks. N Engl J Med 1980: 302:1157-62. Parodi 0, Uthurralt N, Severi S, et al. Transient reduction of regional myocardial perfusion during angina at rest with ST-segment depression or normalization of negative T waves. Circulation 1981;63:1238-47. Goldman BS, Weisel RD, Christakis GT, et at. Predictors of outcome after coronary artery bypass graft surgery for stable and unstable angina pectoris. In: Hugenholtz PG, Goldman BS, eds. Unstable angina. current concepts and management. Stuttgart, Schattauer, 1985. Huret JH, Agier B, Rosier DP, et at. Delayed semielective coronary bypass surgery for unstable angina pectoris. J THORAC CARDIOVASC SURG 1978;75:476-82. Goldman BS, Gunstensen J, Gilbert BW, et at. Increasing operability and survival with intra-aortic balloon pump assist. Can J Surg 1976;19:69-78. Weintraub RM, Youkydis PC, Aroesty JM, et al. Treatment of preinfarction angina with intraaortic balloon counterpulsation and surgery. Am J Cardiol 1974;34:80914. Weintraub RM, Aroesty JM, Paulin S, et al. Medically refractory unstable angina pectoris. 1. Long-term followup of patients undergoing intraaortic balloon counterpulsation and surgery. Am J Cardiol 1979;43:877-82. Williams DO, Korr KS, Gewritz H, Most AS. The effect of intraaortic balloon counterpulsation on regional myocardial blood flow and oxygen consumption in the presence of coronary artery stenosis in patients with unstable angina. Circulation 1982;66:593-7. Aroesty JM, Weintraub RM, Paulin S, O'Grady GP. Medically refractory unstable angina pectoris. II. Hemodynamic and angiographic effects of intraaortic balloon counterpulsation. Am J Cardiol 1979;43:883-8.

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24 Leinbach RC, Buckley MJ, Austen WG, et al. Effects of intraaortic balloon pumping on coronary blood flow and metabolism in man. Circulation 1971;43(Pt 2):177-81. 25 Fuchs RM, Brin KP, Brinker JA, Guzman PA, Heujer RR, Yin Fe. Augmentation of regional coronary blood flow by intraaortic balloon counterpulsation in patients with unstable angina. Circulation 1983;68:117-23. 26 Jett GK, Dengle SK, Barnett PA, Platt MR, Willerson JT, Watson JT. Intraaortic balloon counterpulsation: its influence alone and combined with various pharmacological agents on regional myocardial blood flow during experimental acute coronary occlusion. Ann Thorac Surg 1981;31:144-54. 27 Brawley RK, Merril W, Gott VL, Donahoo JS, Watkins L, Gardner TJ. Unstable angina pectoris. Factors influencing operative risk. Ann Surg 1980;191:745-50. 28 Fremes SE, Christakis GT, Weisel RD, et al. A clinical trial of blood and crystalloid cardioplegia. J THORAC CARDIOVASC SURG 1984;88:726-41. 29 Christakis GT, Fremes SE, Weisel RD, et al. Reducing the risk of urgent revascularization for unstable angina: randomized clinical trial. 1985. J Vase Surg 1986;3:76472. 30 Magovern GJ, Dixon CM, Burkhooder JA. Improved myocardial protection with nifedipine and potassiumbased cardioplegia. J THORAC CARDIOVASC SURG 1981; 82:239-44. 31 Lazar HL, Buckberg GO, Manganaro AJ, Becker H. Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood

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cardioplegia with amino acids during reperfusion. J THORAC CARDIOVASC SURG 1980;80:350-9. 32 Rosenkranz ER, Buckberg GO, Laks H, Mulder DG. Warm induction of cardioplegia with glutamate-enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon support. Initial experience and operative strategy. J THORAC CARDIOVASC SURG 1983;86:507-18.

Appendix Stepwise logistic regression selected each variable in a stepwise fashion and estimated the coefficients for a logistic regression model to predict the probability of postoperative outcome (mortality, myocardial infarction, or low output syndrome). The predictive model has the following form:

1+

,C + PIXI + P2X2 + eC + PIXI + P2X 2 +

+p"X" + poX"

where Xl> X2, ••• , X" are the independent variables and C and PI' P2, ••• , P, are the coefficients generated by the stepwise logistic regression. Step selection was based on the maximum likelihood ratio. A p value of less than 0.15 was required for entry into the model, and a p value greater than 0.10 was required for removal. An improvement chi square was calculated for each variable entered. Variables were considered independently significant if the improvement-of-fit chi square was significant (p < 0.01).