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J Thorac Cardiovasc Surg 1994;107:1317-1322
© 1994 Mosby, Inc.
SURGERY FOR ACQUIRED HEART DISEASE |
Los Angeles, Calif.
From the Department of Cardiac Surgery, Southern California Regional Center, Kaiser Permanente Medical Center, and the University of California, Los Angeles, Calif.
Address for reprints: Colleen F. Sintek, MD, Kaiser Permanente Medical Center, 1505 N. Edgemont St., Los Angeles, CA 90027.
Abstract
At present no consensus exists regarding the timing of surgical revascularization after acute myocardial infarction. Patients admitted with acute myocardial infarction between January 1990 and April 1993 underwent early cardiac catheterization if they had postinfarction ischemia or positive results on a low-level exercise stress test. If indications for surgical intervention were found at the time of catheterization, patients were operated on within 1 or 2 days or were discharged and returned for the operation within 2 to 3 weeks. During this period, we performed 2175 isolated coronary artery bypass graft procedures; 23 patients were operated on within 24 hours of acute myocardial infarction with an operative mortality of 4.4%, 30 patients underwent surgery between 24 and 72 hours after infarction with no deaths, 193 patients were operated on between 3 and 7 days after infarction with an operative mortality of 2.1%, 284 patients underwent revascularization between 1 week and 1 month after infarction with an operative mortality of 1.4%, and the 1645 patients without a recent infarction had a mortality rate of 1.9%. Multivariate statistical analysis was performed to evaluate mortality with these independent variables: reoperative surgery, sex, age, diabetes, timing of infarction, location of infarction, and type (transmural versus subendocardial). Myocardial infarction at any time interval less than 1 month before the operation was not associated with mortality when adjusted by these other risk factors. In addition, no differences were noted in length of stay, stroke rate, or prevalence of renal failure or pulmonary insufficiency. We conclude that nonemergency surgical revascularization can be done safely at any time interval after acute myocardial infarction, certainly after 72 hours, with no increase in operative mortality and acceptable morbidity. (J THORACCARDIOVASCSURG1994;107:1317-22)
Over the past 10 to 15 years, many authors have evaluated the timing of surgery after acute myocardial infarction (AMI). 
1-5 Surgical intervention for AMI may be required when thrombolytic therapy, percutaneous transluminal coronary angioplasty, or both have been unsuccessful and the AMI is less than 6 hours old. Patients with ongoing ischemia, hemodynamic instability, or both, with angiographically confirmed multivessel coronary artery disease, require emergency surgical revascularization. Those patients with the mechanical defect of ventricular septal defect or papillary muscle rupture obviously require prompt surgical attention. The condition of many patients can be stabilized after AMI and they may then be referred for cardiac catheterization because of postinfarction angina or positive results of a noninvasive test for ischemia. On review of the catheterization data and coronary artery anatomy, many of these patients are found to be candidates for surgical intervention. Today there is no consensus regarding the optimal timing of surgical revascularization in this subgroup of patients. In an effort to define the practice patterns that have evolved in our group for management of AMI and to assess the risk of surgical revascularization related to timing of the procedure after AMI, we reviewed our own experience as a large health maintenance organization.
METHODS
The Kaiser Permanente Health Plan is a prepaid Health Maintenance Organization that provides care to approximately 2.2 million members in Southern California. The Los Angeles Medical Center serves as the cardiac surgical referral center for all Kaiser members, except the San Diego area, covering approximately a 120-mile radius. Referral hospitals include ten Kaiser facilities, two of which have cardiac catheterization capabilities, as well as contract hospitals to which patients are referred for investigation and diagnosis of AMI. All of these patients are then funneled through the Los Angeles facility once they have been stabilized for consideration regarding further treatment after AMI.
All patients with AMI who have no contraindication and present less than 6 hours after onset of chest pain receive thrombolytic therapy. Subsequently, they undergo risk stratification and are referred for cardiac catheterization if they have postinfarction angina or positive results on a low-level treadmill test. Every patient undergoing cardiac catheterization is reviewed at a daily combined catheterization–cardiac surgical conference, and individual patient management decisions are made jointly by the cardiologists and cardiac surgeons. If surgical intervention is indicated, most patients are operated on within 1 or 2 days. A few patients who are in clinically stable condition with nonthreatening anatomy are allowed to return home and their operation is scheduled within 2 to 3 weeks.
All patients undergoing isolated revascularization procedures from January 1990 through April 1993 were entered into the study. Patients in full cardiac arrest undergoing cardiopulmonary resuscitation on the way to the operating room (four patients within this time frame) were excluded. This leaves 2175 patients receiving isolated coronary artery bypass grafting during this time interval; 23 patients were operated on within 24 hours of AMI (group 1), 7 patients underwent operation between 24 and 48 hours after AMI (group 2), 23 patients had the operation between 48 and 72 hours of their AMI (group 3), 193 patients were operated on between 3 and 7 days after AMI (group 4), 284 patients underwent revascularization between 1 week and 1 month after AMI (group 5), and 1645 patients had not had an AMI within 1 month of the operation (group 6, control group).
Coronary angiography was performed in all patients before the operation. Vessel stenosis of 50% or more of luminal diameter by angiogram was deemed to be significant. Ventriculograms in the right anterior oblique projection were performed in most patients excluding those with left ventricular end-diastolic pressures greater than 20 mm Hg or significant renal insufficiency, or both. Five segments (anterobasal, anterolateral, apical, diaphragmatic, posterobasal) were analyzed and assigned a numeric score (1, normal; 2, moderate hypokinesis; 3, severe hypokinesis; 4, akinesis; 5, dyskinesis; 6, aneurysm) according to the classification of the Coronary Artery Surgery Study (CASS). 6 A total of 1660 patients had ventriculograms analyzed for wall motion scores. All patient demographic data, preoperative catheterization findings, operative data, and postoperative complications were entered into the computer database during the patient's hospital stay. These data were subsequently retrieved and analyzed.
Transmural infarction was defined as ST-segment changes that progressed to pathologic Q waves, accompanied by characteristic cardiac enzyme abnormalities. Subendocardial infarction was defined as ST-segment and T-wave abnormalities that did not progress to pathologic Q waves, but with abnormal elevation of creatinine kinase (CK) before any intervention. Anterior AMI occurred when changes were confined to the precordial or lateral leads. Changes in the inferior, inferoposterior, posterior, or inferolateral leads were defined as inferior AMI.
The diagnosis of surgical wound infection was made according to the Centers for Disease Control and Prevention criteria. Respiratory insufficiency was diagnosed in patients requiring support with a ventilator for more than 7 days after the operation. Stroke was diagnosed in patients demonstrating a neurologic deficit with positive computed tomographic scan findings (hemorrhagic or nonhemorrhagic infarction). The complication of postoperative AMI was defined as development of new Q waves on the postoperative electrocardiogram or elevation of total CK-MB level above 75 IU/L. Length of stay was defined as days of hospitalization beginning with the date of operation through the day of discharge.
Surgical technique consisted of standard cardiopulmonary bypass with moderate systemic hypothermia. All distal anastomoses were performed during a single crossclamp time with antegrade blood cardioplegic solution in 1:1 dilution being administered in an initial dose of 1000 ml with application of the crossclamp and subsequent 300 ml aliquots being given into the aortic root after completion of each distal anastomosis. Many of these patients received warm induction with glutamate-aspartate blood cardioplegic solution followed by standard blood cardioplegia during the crossclamp time, with warm glutamate-aspartate blood cardioplegic solution being infused just before the aortic crossclamp was removed. Those patients with severe left ventricular dysfunction or instability before cardiopulmonary bypass were selected to receive warm induction and reperfusion cardioplegia as described by Dr. Buckberg (personal communication).
Proximal anastomoses were carried out under partial-occlusion clamping during the rewarming period. Left internal mammary artery grafting was used in all patients younger than the age of 75 years unless they were in unstable condition or had unsuitable targets for in situ left internal mammary artery grafting. Bilateral internal mammary grafts were used in patients younger than the age of 60 years excluding those patients with insulin-dependent diabetes or hemodynamic instability. Intraaortic balloon pump support was initiated if the patient could not be weaned successfully from cardiopulmonary bypass with moderate inotropic support or if electrocardiographic changes were noted, especially ST-segment elevations in an otherwise hemodynamically stable patient.
Data management and statistical analysis
All data were compiled and stored in a computerized data bank on an SCO Unix system (Santa Cruz Operation, Inc., Santa Cruz, Calif.) and were analyzed with the SPSS statistical analysis package (SPSS Inc., Chicago, Ill.). Univariate analyses with Mantel-Haenszel 
2 and Fisher's exact tests where appropriate for discrete variables were used to assess the effect of a number of variables on 30-day mortality and morbidity. Multiple logistic regression was used to select the independent predictors of 30-day mortality. A p value of less than 0.05 was considered significant.
RESULTS
During the study period, 2175 patients underwent isolated coronary revascularization procedures. The average age was 63.4 years (range 32 to 85 years). Forty-eight percent of patients were aged 65 years and older and 244 patients (11.2%) were older than 75 years of age (Table I). Group 5 comprised a statistically higher percentage of female patients than the control group. Group 1 and group 5 contained significantly more patients with diabetes and group 5 had significantly fewer patients with a history of previous revascularization procedures. Six hundred eighty-five patients (42%) in the control group had had previous transmural AMIs more than 1 month before coronary artery bypass grafting. The average wall motion score for each group is listed in Table II. Only 48%, 57%, and 65% of patients in groups 1, 2, and 3, respectively, had wall motion scores calculated because left ventriculograms were not performed. Most of these patients had left ventricular end-diastolic pressures greater than 20 mm Hg and therefore had significant left ventricular dysfunction and would be expected to have higher wall motion scores if they had undergone left ventriculography.
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Table III). A significantly lower percentage of patients in groups 1 and 4 had internal mammary artery grafting than in the control group. Intraaortic balloon pump support was required in 4.3% of group 1, 14.3% of group 2, 8.7% of group 3, 2.6% of group 4, 3.9% of group 5, and 2.6% of group 6 patients. No significant difference in the need for intraaortic balloon pump placement was observed in any study group compared with the control group.
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Table IV). The postoperative AMI rate is significantly higher in group 5 patients. The average length of hospital stay for all six groups is similar, ranging from 8.0 to 10.6 days with no statistically significant difference noted in any group compared with the control group.
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Table V). According to univariate analysis, the operative mortality is significantly higher in female patients in group 6. Some studies have suggested that anterior transmural AMI is an important predictor of 30-day mortality when the operation is performed in the early post-AMI period. 7,8 Table VI summarizes the mortality rates for the 202 patients undergoing revascularization within 1 month of an anterior AMI. Although one death occurred among the four patients with transmural infarctions in group 1, this increased mortality rate is not statistically significant by univariate analysis because of the small numbers involved. Wall motion score was analyzed as an independent risk factor for mortality and shows a significant association only in group 6 patients, with wall motion scores greater than 7.
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Table VII). As can be seen, the confidence intervals for groups 1, 2, and 3 are wide, so that the conclusion that there is no difference in mortality rates for these three groups is not certain. A greater number of patients would have to undergo surgery within 72 hours of AMI for any definite conclusion to be reached.
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Discussion
Before the 1970s, the treatment of AMI consisted mainly of bedrest for a period of several days to several weeks. Beginning in the early 1970s, acute surgical intervention was introduced by the group in Spokane, Washington. 2 This group demonstrated that early surgical reperfusion, that is, less than 6 hours after the onset of AMI, was associated with an impressively low in-hospital mortality rate that was sustained in a 10-year follow-up period. However, this approach was not readily applicable to the population at large, basically because of procedural delays, enormous costs, and a lack of general availability. Only 20% of all hospitals in the United States have catheterization laboratory facilities and even fewer have the capabilities of undertaking cardiac surgery on a 24-hour a day standby basis. 9
In the 1980s, thrombolytic therapy revolutionized the treatment of AMI, and many multiinstitutional studies have verified its effectiveness at decreasing the mortality of AMI and preserving left ventricular function. 10-14 However, thrombolytic therapy affects only the acute thrombus and has no effect on the underlying atherosclerotic lesion or stenosed non-infarct-related vessels. These constitute a potential source of continued myocardial ischemia. In addition, it is estimated that only 25% to 35% of all patients who have had an AMI qualify for thrombolytic therapy. Some patients require emergency intervention after AMI because of mechanical problems or evidence of ongoing ischemia. Those patients whose condition can be stabilized may be candidates for elective revascularization. This analysis of all patients undergoing nonemergency isolated coronary artery revascularization demonstrates that timing of the procedure after AMI, certainly after 72 hours, is not associated with increased operative mortality. The length of hospital stay is not increased when patients are operated on in the early postinfarction period. A statistically significant increase in the rate of wound infection (1.6%) was noted in patients undergoing revascularization between 3 and 7 days after AMI, and a significantly higher postoperative AMI rate (2.8%) was found in patients operated on between 1 week and 1 month of AMI. These increased complication rates are well within the acceptable range. This retrospective analysis did not identify any subgroup of patients who might benefit from a period of stabilization before surgical intervention after AMI.
Appendix: DISCUSSION
Dr. Forrest L. Junod (Sacramento, Calif.).
Our experience supports the efficacy and safety of early operation in patients with AMI and also raises some questions. A total of 1543 patients had coronary artery bypass in the 2 years 1991 and 1992 at Sutter Memorial Hospital, Sacramento, California. The operative mortality was 2.3% (36/1543). Four hundred forty patients had the operation in the presence of AMI.
For first-time operations, coronary artery bypass in patients with AMI showed a mortality of 3.3% (13/389), significantly greater than in patients having coronary bypass without AMI, who had an operative mortality of 1.0% (10/955) (p < 0.01).
For all repeat coronary artery bypass operations an operative mortality of 6.5% was experienced. Although mortality and morbidity were increased over first-time operation, AMI did not alter mortality significantly in the patients having repeat operations. Perhaps the small sample size, 51 patients with four deaths, did not permit differentiation from those without infarcts.
Although operative mortality is a measure of operative risk, it is a poor correlate for operative benefit. Operative mortality is of little benefit in assessing the result for survivors. In your report, for example, 33% of patients had transmural infarcts if operated on within 1 week, whereas 80% had transmural infarcts if operated on 1 week to 1 month after AMI. The increase in transmural AMIs may be a consequence of delay or the result of selection.
About 10% of your patients were operated on in 7 days, compared to 95% in our series. In your report less than 3% (53/2175) were operated on in the first 3 days, as compared with 16% of all patients in our data. Difference in sample size, coupled with exclusion of patients in unstable condition, will affect conclusions regarding the timing and risk of surgical treatment.
Internal mammary artery grafting is suggested to confer protection against mortality in patients operated on within 1 week of an AMI. The Methods section indicated that patients older than 75 years of age, or who are in unstable condition or without suitable targets, were excluded from internal mammary artery grafting. The same reasons are frequently used in our series. Patients with internal mammary artery grafts may survive better, but the finding may be one of selection rather than protection.
While preparing these comments, I was struck by the difficulty of clinically identifying the extent and reversibility of myocardial ischemia. What electrocardiographic change, enzyme elevation, scan data, or wall motion abnormality characterizes the degree of damage or potential recovery? How is myocardial ischemia, with and without permanent damage, to be evaluated both before and after any treatment method? Definition of patients at risk and adequate review of all methods of therapy are needed for better patient care.
Excellent results in patients having coronary bypass after recent AMI lead the authors to propose operative treatment in the early postinfarct period to avoid the complications of reinfarction and death, as well as the added expense and uncertainty of rehospitalization. AMI remains a factor of increased risk for coronary artery bypass in our experience, although the added risk is small. Delay may be worse.
I have some questions for Dr. Sintek: How was AMI defined? Was one test acceptable or was a combination needed to confirm the diagnosis? What happened to the patients who were in unstable condition? Was an attempt made to delay beyond 3 days for stability? About one third of our AMI patients had thrombolysis and only 2% had angioplasty. What were these treatment modalities in your series?
Dr. Sintek.
Thank you, Dr. Junod. First to clarify the issue of transmural AMIs: 33% of patients who were operated on within 1 week of AMI had had transmural as opposed to subendocardial infarctions. The postoperative AMI rate for this group of patients was less than 1%. Eighty percent of patients operated on between 1 week and 1 month of their infarction had had transmural infarctions before the operation. This group had a postoperative AMI rate of 2.8%. In addition, 246 patients (46.4%) underwent surgery within 7 days of AMI, not 107, as you indicated.
To address your first question regarding AMI: Transmural AMI was defined as ST-segment changes that progressed to pathologic Q waves accompanied by elevated CK-MB levels. Subendocardial infarction was defined as ST-segment and T-wave abnormalities that did not progress to pathologic Q waves but with abnormal elevation of CK-MB before any intervention.
This study did not exclude any patients in unstable condition. In no case was surgery delayed in an effort to stabilize the patient before operative intervention. The only patients excluded from this study were patients brought to the operating room with cardiopulmonary resuscitation in progress for a so-called salvage procedure. A probable explanation for the finding that fewer of our patients were operated on within 1 week of their AMI is the distribution of the population that the Kaiser–Los Angeles Cardiac Surgery Department serves. Kaiser members having an AMI are admitted to other facilities or contract hospitals and then transferred to our facility only if they are believed to require urgent cardiac catheterization and possible surgical intervention. This may well explain the time delay from the day of infarction to the day of operation.
Regarding thrombolysis and angioplasty, I do not have the exact figures available for AMI patients treated at Kaiser facilities during this time period.
Acknowledgments
We express our sincere appreciation to Timothy DuFrene, Janis Fan-Fang Yao, and Girma Wolde-Tsadik, PhD, for their expert assistance in the statistical analysis of the data.
Footnotes
Read at the Nineteenth Annual Meeting of The Western Thoracic Surgical Association, Carlsbad, Calif., June 23-26, 1993. 
References
This article has been cited by other articles:
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  P. Sorajja, B. J. Gersh, D. A. Cox, M. G. McLaughlin, P. Zimetbaum, C. Costantini, T. Stuckey, J. E. Tcheng, R. Mehran, A. J. Lansky, et al. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction Eur. Heart J., July 2, 2007; 28(14): 1709 - 1716. [Abstract] [Full Text] [PDF]
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 P. Voisine, P. Mathieu, D. Doyle, J. Perron, R. Baillot, G. Raymond, J. Metras, and F. Dagenais Influence of time elapsed between myocardial infarction and coronary artery bypass grafting surgery on operative mortality Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 319 - 323. [Abstract] [Full Text] [PDF]
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 D. C. Lee, M. C. Oz, A. D. Weinberg, and W. Ting Appropriate timing of surgical intervention after transmural acute myocardial infarction J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 115 - 120. [Abstract] [Full Text] [PDF]
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 D. C. Lee, M. C. Oz, A. D. Weinberg, S. X. Lin, and W. Ting Optimal timing of revascularization: transmural versus nontransmural acute myocardial infarction Ann. Thorac. Surg., April 1, 2001; 71(4): 1198 - 1204. [Abstract] [Full Text] [PDF]
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L. L. Creswell, M. J. Moulton, J. L. Cox, and M. Rosenbloom Revascularization After Acute Myocardial Infarction Ann. Thorac. Surg., July 1, 1995; 60(1): 19 - 26. [Abstract] [Full Text]
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T. K. Kaul, B. L. Fields, S. L. Riggins, G. C. Dacumos, D. A. Wyatt, and C. R. Jones Coronary Artery Bypass Grafting Within 30 Days of an Acute Myocardial Infarction Ann. Thorac. Surg., May 1, 1995; 59(5): 1169 - 1176. [Abstract] [Full Text]
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