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J Thorac Cardiovasc Surg 1995;110:971-978
© 1995 Mosby, Inc.

SURGERY FOR ACQUIRED HEART DISEASE

DETERMINANTS OF OPERATIVE MORTALITY IN REOPERATIVE CORONARY ARTERY BYPASS GRAFTING

Portland, Ore., Hong Kong, and Dallas, Tex.

Supported in part by St. Vincent Medical Foundation, Portland, Ore.

Received for publication Sept. 29, 1994. Accepted for publication Jan. 20, 1995. Address for reprints: Guo-Wei He, MD, PhD, Professor, Chair of Cardiothoracic Surgery, Department of Surgery, University of Hong Kong, The Grantham Hospital, 125 Wong Chuk Hang Rd., Aberdeen, Hong Kong.

Abstract

Previously suggested risk factors for operative mortality in reoperative coronary artery bypass grafting are contradictory. Therefore, we analyzed our data of 622 patients who underwent reoperative bypass grafting from January 1986 through June 1993. Among these patients, 258 had saphenous vein grafts alone and 364 had internal mammary artery grafting, including unilateral (342 patients) and bilateral (22 patients) mammary artery grafting with or without additional saphenous vein grafting. Overall operative mortality was 11.4% for reoperation compared with only 3.6% for primary bypass grafting during the same time frame. To determine risk factors for mortality and the influence of internal mammary artery grafting on the outcome, we analyzed 82 variables (31 preoperative, 17 intraoperative, and 34 postoperative) by univariate analysis. Significant variables or the variables having a trend (p < 0.2) to be associated with the mortality were included in stepwise multiple logistic regression analyses. Two regression analyses were separately performed. Regression 1 only included preoperative and intraoperative variables whereas regression 2 included postoperative variables as well. The logistic regressions demonstrate that preoperative variables (low ejection fraction [p = 0.0002], old age [p = 0.003], female gender [p = 0.011], and history of arrhythmia [p = 0.023]), intraoperative variables (emergency operation [p = 0.0001] and long perfusion time [p = 0.0001]), and postoperative variables (complications) are independently associated with higher mortality. Unlike previously described results, aortic crossclamp time, route of cardioplegia, use of internal mammary artery, number of grafts, and year of operation are not associated with operative mortality. The identification of these risk factors may have important implications in further improvement of the results of reoperative coronary artery bypass grafting. (J THORAC CARDIOVASC SURG 1995;110:971-8)

Coronary artery bypass grafting (CABG) has been performed in large number of patients since its introduction in the 1960s. With the increasing number of the patients who have undergone CABG, the incidence of reoperative CABG is also increasing. In an early report, the reoperative incidence for CABG is approximately 3% at 5 years, higher than 11% at 10 years, and 17% at 12 years. ¹ Other reports have given an incidence of reoperation at a range of 3% to 8.65%. ^2-6 Therefore, a large patient population after the primary CABG will be at high risk of reoperation. The Society of Thoracic Surgeons (STS) national database experience also indicates that the incidence of reoperation for CABG has a progressive increase, from 1.9% in 1980 to 7.0% in 1990. ⁷ It is widely documented that reoperative CABG carries a higher mortality than primary CABG, ranging from 3.4% to 12.5%. ^3-11 However, although risk factors for operative mortality or long-term survival were studied, apart from the experience from the Cleveland Clinic, ^8-11 little information on such factors is available. In addition, in studies regarding risk factors for coronary reoperations the determinants for operative mortality demonstrated from one study are not corroborated by another. For example, a study from the Cleveland Clinic ⁸ has identified that the independent risk factors for reoperative CABG are left main disease, New York Heart Association functional class III or IV, advanced age, year of operation, and incomplete revascularization. However, another study has shown that the only risk factor for reoperative CABG is emergency or urgent operation. ³

Furthermore, the risk factors may also change the pattern from time to time because of the more advanced management. We recently reviewed our cases of isolated CABG during 1986 to 1993 and found that year of operation is no longer correlated with operative mortality. We speculate that this obviously reflects the maturity of surgical, anesthesiologic, medical, and nursing management for CABG. This improvement may be also true in reoperative CABG. Therefore, in the present study, we retrospectively reviewed the data of reoperative CABG in Dallas since the middle 1980s in an attempt to provide new information for determinants of operative mortality.

PATIENTS AND METHODS

From January 1986 through June 1993, isolated CABG was performed in 6360 patients by Cardiothoracic Surgery Associates of North Texas surgeons in Dallas, Texas. Of these patients, 622 were having reoperations. One hundred forty-one patients were operated on between 1986 and 1988, 322 between 1989 and 1991, and 159 between 1992 and 1993. Inasmuch as the STS database included a field of reoperative reason (June 1992), the reason for reoperation was recorded in 102 patients. The reasons were prior saphenous vein graft occlusion (n = 46), prior internal mammary artery (IMA) graft occlusion (n = 3), prior IMA and saphenous vein occlusion (n = 1), and progression of native coronary disease (n = 52). The mean age of these patients was 62.1 ± 0.4 years (range 36.4 to 93.0 years). Patients who had concomitant valve operations or resection of ascending aortic aneurysm were excluded from this study. Among these patients, 258 had saphenous vein grafting alone and 364 had IMA grafting, including unilateral (n = 342) and bilateral (n = 22) IMA grafting with or without additional saphenous vein grafting. A computerized cardiac surgery registry based on the STS database provided the basis for this study. Operative death was defined as any in-hospital death and all out of hospital deaths occurring within 30 days after operation.

The clinical characteristics were recorded by cardiologists. The criterion of obesity was based on the body mass index. Body mass index was calculated by dividing measured body weight in kilograms by the height in meters squared. A body mass index greater than 27.5 kg/m ² (over 120% "normal" body mass index) was considered as obesity. ¹² Perioperative myocardial infarction was defined as new Q waves and was diagnosed by cardiologists or surgeons.

Catheterization data
All patients underwent preoperative left heart catheterization and coronary angiography. Patients were grouped into categories of single, double, and triple vessel disease. Significant coronary artery disease was defined as 70% or more stenosis in any view of the right, left anterior descending, left circumflex artery, or their major branches. Left main artery disease was defined as 50% or more stenosis. Left ventricular ejection fraction was calculated according to left ventriculography. Left ventricular function was classified as normal (ejection fraction 50%) and mild (ejection fraction 40% to 50%), moderate (ejection fraction 30% to 39%), or severe (ejection fraction <30%) dysfunction. Stenosis of coronary artery branches was classified as up to 50%, 51% to 70%, 71% to 90%, 91% to 99%, and 100%.

History of congestive heart failure was defined by the cardiologists in terms of cardiac failure in the patient's history that necessitated medical treatment. History of arrhythmia included ventricular arrhythmia, atrioventricular block, or atrial fibrillation recorded in the patient's chart. The decision for emergency operation was made by the cardiology and cardiac surgery teams together. This refers a need for emergency operation immediately. Low cardiac output was defined as cardiac index less than 2.5 L/m ² with clinical symptoms (systemic hypotension and low urine output). Insertion of an intraaortic balloon pump included preoperative (11 patients), intraoperative (16 patients), and postoperative (4 patients) insertion. Indications for intraaortic balloon pumping were unstable angina, low cardiac output, inability to be weaned from cardiopulmonary bypass, and shock. Perioperative myocardial infarction was defined as new Q waves. Stroke was defined as neurologic deficiency that appeared after the operation, either transient (recovery before discharge) or permanent (remained on discharge). Renal failure was defined as increased creatinine concentration (2.5 mg/dl). Pulmonary complications were defined as one or more of the following: ventilatory assistance for more than 5 days, pulmonary insufficiency, pulmonary embolism, pneumonia, adult respiratory distress syndrome, or need for a tracheostomy.

Operative technique
The conduct of reoperative surgery always requires flexibility to adjust to intraoperative findings. However, certain principles were standard during the course of this study. Except for emergency or unusual preoperative concerns, cannulation was performed through the redo sternotomy, which was carefully made with an oscillating saw. After the heart was dissected away from the sternum, the right atrium and aorta were exposed starting at the diaphragmatic surface of the heart. This would allow early cannulation if cardiac decompensation occurred. Attempts were made to avoid manipulation of patent grafts as much as possible, but cardioplegic arrest of the heart was not routinely performed before determination of the distal sites for coronary bypass. Antegrade cardioplegia was used throughout this experience. When retrograde cardioplegia became commonly available (since 1990), hypothermic crystalloid retrograde cardioplegia was adopted for all redo procedures in combination with antegrade cardioplegia. Cardioplegic solution was also given through each completed vein graft. Moderate systemic hypothermia was used during cardiopulmonary bypass. Proximal anastomoses were most often performed after removal of the aortic crossclamp to decrease the period of ischemic arrest. Weaning from bypass and sternal closure followed usual protocol.

Statistical analysis
The correlation between preoperative, intraoperative, and postoperative variables and operative mortality was tested by univariate analysis; operative mortality and operative morbidity were compared between the IMA and saphenous vein graft groups, as well. Univariate testing of variables was performed with ² analysis or Fisher's exact test on discrete variable comparisons. The unpaired t test was used on continuous variable comparisons. To investigate the influence of IMA grafting on the operative mortality, we separately tested IMA grafting and unilateral, bilateral, and right IMA grafting. After the univariate analysis, stepwise multiple logistic regression analysis was used to further test significant variables in a multivariate situation. ^13-19 Any variables that had trend associated with operative mortality (p < 0.2) were also included in stepwise multiple logistic regression analysis. The univariate analysis and the logistic regression were performed with the SAS Program (SAS Institute Inc., Cary, NC) in an IBM compatible personal computer linked with a VAX computer (Digital Equipment Corp., Maynard, Mass.). A p value of less than 0.05 was considered significant.

RESULTS

Univariate analysis
Overall operative mortality was 11.4%. The causes of death are listed in Table I. Univariate analysis was performed for 82 variables to determine the risk factors correlated to the operative mortality in patients undergoing reoperative CABG. These variables included 31 preoperative, 17 intraoperative, and 34 postoperative (see the appendix). Tables II and III list significant variables for operative mortality. Some statistically insignificant but particularly concerned variables (such as year of operation or number of reoperations) are also listed. No difference in operative mortality was detected among different years of operation. The average age of operative survivors (61.8 ± 0.4 years) was younger than that of nonsurvivors (64.4 ± 1.1 years, p = 0.024). Female patients had higher mortality (19.0%) than male patients (10.1%, p = 0.012). Other preoperative variables associated with the operative mortality were height, diabetes, cardiomegaly, history of congestive heart failure, myocardial infarction, or arrhythmia, angina, New York Heart Association class, left ventricular ejection fraction, left ventricular function, stenosis of the left anterior descending coronary artery, and previous percutaneous transluminal coronary angioplasty. Perioperative (intraoperative and postoperative) variables associated with operative mortality (p < 0.2) were emergency operation, surgeons, number of grafts, IMA grafting or saphenous vein grafting, unilateral IMA grafting versus saphenous vein grafting, perfusion time, intraaortic balloon pumping, and postoperative complications (Table III) including postoperative low cardiac output, reoperation for bleeding, septicemia, stroke (permanent), pulmonary complications, ventilatory support for more than 5 days, and renal failure.

This study demonstrates that long perfusion time, emergency operation, low ejection fraction, old age, female gender, history of arrhythmia, and postoperative complications are independent determinants of operative mortality for reoperative CABG.

With an increased need for reoperation in patients who have undergone primary or reoperative CABG, studies on risk factors for the operative mortality for reoperation in those patients have attracted more attention recently. ^5-8 This is particularly important in reoperative CABG because it carries higher mortality than primary CABG. ^3,6,7 Although the Cleveland Clinic ⁸ reported an operative mortality for reoperative CABG of 3.4%, most centers have reported a higher operative mortality, up to 12.5% ² with a median of about 6% to8%. ^3,6,7 In our study, although the operative mortality for reoperation was high, in our patients undergoing primary CABG the operative mortality was only 3.6% (205/5738) during the same time frame. Application of multivariable logistic regression analysis makes risk analysis possible. The risk factors identified by the Cleveland Clinic ¹⁰ in early 1980s are incomplete first operation, incomplete reoperation, left main coronary artery disease (greater than 50% stenosis), and advanced age. However, in their later study, ⁸ the risk factors changed into left main stenosis, class III or IV symptoms, advanced age, early year of reoperation, and incomplete revascularization. This indicates that the risk factors may change their pattern with increased experiences in surgical, medical, anesthesiologic, and nursing management. On the other hand, the risk factors identified from one cardiac surgical center may not be demonstrated by another. In contrast to the studies from the Cleveland Clinic, a report from the New York Hospital–Cornell Medical Center ³ suggests that the only risk factor for operative mortality in reoperative CABG is emergency or urgent operation. The diverse results from these two centers prompt such analysis from other data sets.

In the present study, we have investigated the risk factors for reoperative CABG. Our study was primarily focused on preoperative and intraoperative variables because they are more important than postoperative variables in predicting operative mortality. We have found that although many preoperative and intraoperative variables are associated with a higher mortality by univariate analyses, the independent variables are long perfusion time, emergency operation, low ejection fraction, old age, female gender, and a history of arrhythmia. Among these predictors, the strongest are long perfusion time and emergency operation. This is demonstrated by the fact that these two variables remained in the second logistic regression model (Table V), in which the strong influence of postoperative complications (low cardiac output, intraaortic balloon pump, stroke, and renal failure) was included.

In a previous report, ³ long perfusion time was not an independent risk factor for reoperative CABG although it was significant in univariate analysis. Our study suggests that this variable is the strongest predictor for operative mortality in patients undergoing reoperative CABG. The mean perfusion time for nonsurvivors (172.7 ± 7.9 minutes) was significantly longer than that for survivors (125.9 ± 1.8 minutes) (Table III). In contrast, the difference in aortic crossclamp time between operative survivors and nonsurvivors was not significant (Table III). Accordingly, there were no differences between survivors and nonsurvivors regarding the number of grafts, although in general long aortic crossclamp time is required when more grafts are performed. As indicated in a previous study, ¹⁶ a long cardiopulmonary bypass time is related to (1) long aortic crossclamp time and (2) long reperfusion time. Usually, a long aortic crossclamp time reflects the complexity of the operation and a long reperfusion time implies that the heart requires longer support by a cardiopulmonary machine. Therefore long cardiopulmonary bypass time may be more important to reflect the cardiac functional status after ischemia, that is, during the reperfusion period.

A recent study ³ has suggested that emergency operation is the only risk factor for reoperative CABG determined by multivariate analysis. Our study is in agreement, although we have found other risk factors as well. In the present study, emergency operation carries a significantly higher mortality (Table III) and is an independent risk factor for mortality (Table IV).

Four preoperative variables are independent risk factors for operative mortality in reoperative CABG: low ejection fraction, old age, female gender, and a history of arrhythmia. The survivors had higher ejection fractions than the nonsurvivors (48.8% ± 0.6% versus 41.5% ± 1.7%, Table II). This difference obviously reflects the important role of preoperative cardiac function on outcome. However, although the study by the Cleveland Clinic ⁸ suggests that functional class III or IV is a risk factor for operative mortality in reoperative CABG, the present study has demonstrated that this variable did not enter into the logistic regression model as an independent factor, despite the fact that it is significant in univariate analysis (Table II). Therefore, our study has demonstrated that ejection fraction is more important than functional class in predicting the outcome of reoperative CABG.

The influence of age on the outcome for patients undergoing either primary or reoperative CABG have been demonstrated. ^7,8 The findings in our study confirm the role of advanced age on mortality. First, the survivors were younger than the nonsurvivors (61.8 ± 0.4 versus 64.4 ± 1.1 years, Table II). Second, age is an independent variable correlated with operative mortality, demonstrated by the multivariable logistic regression (Table IV). Similarly, female gender is correlated to the mortality. In the present study, women had a higher mortality than men (19.0% versus 10.1%, Table II), and this variable entered into the logistic regression model. In contrast, none of the previous studies suggested that gender was a risk factor, ^1-9 although female gender has been repeatedly demonstrated as an independent risk factor for both operative mortality ⁷ and late survival ^7,21 in primary CABG.

Another risk factor is history of arrhythmia. A number of preoperative variables examined in the present study were associated with mortality from univariate analysis, as shown in Table II. These variables are diabetes, cardiomegaly, history of congestive heart failure, history of myocardial infarction, angina, and history of arrhythmia. However, history of arrhythmia is the only one entered into the multivariable logistic regression model. This predictor has not been previously found ^1-9 and it may have a role in predicting the outcome.

Left main artery disease has been suggested as a risk factor for reoperative CABG. ⁸ However, this is not supported by our study (Table II). Perhaps the recent advances in surgical technique have improved the management for patients who have left main coronary stenosis.

With regard to the use of the IMA in reoperative CABG, the present study examined the mortality for patients who have received the IMA (left, right, or both) as grafts. More than half of our patients received one or two IMAs (Table III). No differences were detected among these subgroups of patients regarding mortality. The role of the IMA in primary CABG has been well demonstrated. ²² The present study also supports the extensive use of the IMA in reoperative CABG. Indeed, the need for use of this arterial graft is even higher than for primary CABG. In 45.1% of patients (46/102) whose operative indication was recorded, the reason for the reoperation was occlusion of previous saphenous vein grafts. As to the safety of using the IMA in reoperative CABG, in our multivariable logistic regression analysis, neither IMA nor saphenous vein grafting was an independent risk factor. Therefore, with present techniques for reoperative CABG, neither IMA nor vein graft seems to affect the operative mortality or morbidity. The influence of the selection of the graft may be more important in reference to long-term results than to operative mortality.

An interesting aspect in regard to myocardial protection is route of cardioplegia. Theoretically, use of retrograde cardioplegia in combination with antegrade cardioplegia may provide better myocardial protection, particularly in patients who have severe coronary artery disease in which antegrade perfusion of the coronary artery may not be effective to reach the microvascular bed and myocardium. However, retrograde cardioplegia was only demonstrated to be superior in high-risk CABG reoperations. ³ In the present study there were no differences in the operative mortality between the patients who received retrograde cardioplegia and the patients who only received antegrade cardioplegia. As seen from Table III, the operative mortality was similar in both groups.

In conclusion, the present study emphasizes that long perfusion time, emergency operation, low ejection fraction, old age, female gender, and history of arrhythmia are risk factors for reoperative CABG. Route of cardioplegia and use of the IMA do not independently affect the mortality.

Appendix: APPENDIX: Variables examined by univariate analysis for operative mortality in the patients undergoing reoperative CABG

Preoperative variables
Sex, age, weight, height, body surface area, smoking history, family history of coronary artery disease, diabetes, obesity, body mass index, hypercholesterolemia, hypertension, chronic obstructive pulmonary disease, history of myocardial infarction, history of congestive heart failure, history of arrhythmia, angina, New York Heart Association functional class, ejection fraction, left ventricular function (classified by ejection fraction), number of vessels diseased, left main disease, right main artery disease, degree of right coronary artery disease, quality of right coronary artery, conduit on right coronary artery, stenosis of left anterior descending coronary artery, distal disease of left anterior descending coronary artery, conduit on left anterior descending coronary artery, previous percutaneous transluminal coronary angioplasty, time from angioplasty to operation.

Intraoperative variables
Year of operation, emergency operation, individual surgeons, aortic crossclamp time, cardiopulmonary bypass time, number of grafts, graft to left anterior descending coronary artery, type of cardioplegia, route of cardioplegia, IMA grafting, unilateral IMA grafting versus saphenous vein grafting, bilateral IMA grafting versus others, bilateral versus unilateral IMA grafting, right IMA grafting versus others, right IMA grafting versus other IMA grafting, left ventricular aneurysmectomy.

Postoperative variables
Postoperative complications, operative complications, reoperation for bleeding, reoperation for graft occlusion, reoperation for cardiac reason, reoperation for noncardiac reason, postoperative low cardiac output, perioperative myocardial infarction, blood product transfusion, packed cell transfusion, units of packed cell transfusion, fresh frozen plasma transfusion, units of fresh frozen plasma transfusion, cryoprecipitate transfusion, units of cryoprecipitate transfusion, platelet transfusion, units of platelet transfusion, infectious complications, sternal infection (superficial and deep), infection of legs, infection of intraaortic balloon pump site, septicemia, neurologic complications, transient stroke, permanent stroke, intraaortic balloon pumping, pulmonary complications, ventilatory support for more than 5 days, pulmonary embolism, pulmonary insufficiency, pneumonia, tracheostomy, adult respiratory distress syndrome, renal failure.

Acknowledgments

We thank Dr. Cheng-Qin Yang for her invaluable assistance in preparation of this manuscript and Mrs. Cathy Walker for her assistance in collecting data.

Footnotes

From The Albert Starr Academic Center for Cardiac Surgery, ^a St. Vincent Heart Institute, Portland, Ore., Department of Surgery, ^a University of Hong Kong, The Grantham Hospital, Hong Kong, and Cardiothoracic Surgery Associates of North Texas at Medical City Dallas Hospital, ^b Dallas, Tex.

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