T conduit of choice for coronary artery bypass grafting. Risks of Bilateral Internal Mammary Artery Bypass Grafting

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1 Risks of Bilateral Internal Mammary Artery Bypass Grafting Nicholas T. Kouchoukos, MD, Thomas H. Wareing, MD, Suzan F. Murphy, RN, Cheryl Pelate, RN, and William G. Marshall, Jr, MD Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri Although use of one internal mammary artery (IMA) for coronary artery bypass grafting does not appear to be associated with increased risk, the results with both IMAs are less certain; the potential for a higher incidence of sternal wound infection as a result of devascularization of the sternum is a major concern. During a 42- month interval ending July 1988, 1,566 patients had coronary artery bypass grafting alone or in combination with other procedures: 633 received only vein grafts, 687 had unilateral IMA grafting, and 246 had bilateral IMA grafting. The IMA patients were younger, were more often male, had better cardiac function, and underwent fewer emergent, urgent, or combined procedures than the patients receiving vein grafts (p < 0.05). Thirty-day mortality was lower among the IMA patients (unilateral IMA group, 2.8%; bilateral IMA group, 3.7%; and vein graft group, 7.9%; p = 0.001). With the exception of sternal wound problems, occurrence rates for postoperative complications among the IMA patients did not differ significantly from or were lower (p < 0.05) than those among the patients with vein grafts. Sternal infections occurred with greater frequency among the bilateral IMA patients (6.9%) than among the unilateral IMA (1.9%) or vein graft (1.3%) patients (p = 0.001). By univariate analysis, obesity, diabetes, bilateral IMA grafting, and need for prolonged (>48 hours) mechanical ventilation were associated with a significantly higher incidence of sternal infection (p < 0.05). Multivariate logistic regression analysis identified use of bilateral IMA grafts (p = O.OOOl), obesity (p = ), and prolonged mechanical ventilation (p = ) as significant risk factors for the development of sternal infection. We conclude that bilateral IMA grafting is an important predictor of sternal infection. It should be used selectively in obese or diabetic patients and in patients who are likely to require prolonged mechanical ventilation postoperatively. (Ann Thorac Surg 1990;49:210-9) he internal mammary artery (IMA) is currently the T conduit of choice for coronary artery bypass grafting (CABG). Although the use of one IMA does not appear to be associated with increased operative risk, the results with both IMAs are less certain. A major concern when both IMAs are used is the potential for a higher incidence of sternal wound complications, presumably as a result of devascularization of the sternum [l-51. We have reviewed our entire experience with CABG during a recent 3%-year interval to determine if use of bilateral IMA grafts is associated with increased risk, and to identify those variables that are predictive of an increased risk of sternal wound infection. Material and Methods Patients Between January 1985 and July 1988, 1,566 patients underwent CABG alone or in combination with other procedures (resection of ventricular aneurysm or infarct, repair of rupture of the ventricular septum, valve replacement or repair, replacement of the ascending aorta and Presented at the Twenty-fifth Anniversary Meeting of the Society of Thoracic Surgeons, Baltimore, MD, Sep 11-13, Address reprint requests to Dr Kouchoukos, Jewish Hospital at Washington University Medical Center, 216 S Kingshighway Blvd, St. Louis, MO arch, and carotid endarterectomy). Vein grafts (VGs) only were used in 633 patients, one IMA graft was used in 687 patients, and bilateral IMA grafts were used in 246 patients. Vein grafts were also used in 864 (93%) of the 933 patients receiving IMA grafts. Clinical Presentation The preoperative characteristics of the patients in the three groups are shown in Table 1. Diabetes was considered present in patients who were receiving insulin or oral hypoglycemic agents or who had been placed on carbohydrate- and calorie-restricted diets by a physician. Hypertension was defined as a resting blood pressure of 140/90 mm Hg or higher; it was also considered present in patients who were receiving antihypertensive medication. To evaluate the effect of obesity, the body mass or the Quetelet index (body weight in kilograms divided by the square of the height in meters) was used [4, 51. This expression of weight in relation to height has a better correlation to body fat than other height-weight relationships. At 30 kg/m2 or more, obesity and overweight are essentially synonymous. Above this level, mortality for coronary heart disease for both men and women increases [5]. Chronic obstructive pulmonary disease was considered present in patients with characteristic findings on roentgenograms (pulmonary hyperinflation, flattened diaphragms, and oligemia of the peripheral lung fields) or on diagnostic pulmonary function tests. Angina pectoris by The Society of Thoracic Surgeons /90/$3.50

2 Ann Thorac Surg 1990;49:21G9 KOUCHOUKOS ET AL 211 was defined according to the Canadian Cardiovascular Society classification [6]. Cutheterizut ion Du tu The extent of coronary artery disease is shown in Table 2. Stenoses greater than 50% to 60% of the luminal diameter were considered hemodynamically significant. Patients were classified as having one-vessel, two-vessel, threevessel, or left main coronary artery disease. Major stenoses in the large diagonal or obtuse marginal branches were considered lesions of the anterior descending or circumflex coronary arteries, respectively. Ventriculography was performed in the right anterior oblique projection. Five segments (anterobasal, anterolateral, apical, diaphragmatic, and posterobasal) were analyzed and assigned a numerical score (1 = normal; 2 = moderate hypokinesis; 3 = severe hypokinesis; 4 = akinesia; 5 = dyskinesia; and 6 = aneurysm) according to the classification of the Coronary Artery Surgery Study [7]. Ventriculograms suitable for analysis were available for 1,381 (88%) of the 1,566 patients. Perioperative Protocol All operations were performed by or under the direct supervision of two surgeons (N.T.K., W.G.M.) using a standardized technique. Cardiopulmonary bypass with moderate core hypothermia (24" to 28 C) and hemodilution was used in all patients. The IMAs were mobilized with a pedicle from the bifurcation into the superficial epigastric Table 1. Preoperative Characteristics of the Patient Groups' Vein Grafts Unilateral Bilateral Only IMA Graft IMA Grafts Variable (n = 633) (n = 687) (n = 246) Mean age (yr) Age 2 65 yr Male sex Diabetes Hypertension Obesity index 2 30 kglm' Chronic obstructive pulmonary disease History of smoking Previous myocardial infarction History of congestive failure CCS class 11-IV Previous cardiac operation More than two days from admission to opera tion (76) 289 (42) 372 (59) 501 (73) 167 (26) 174 (25) 386 (61) 415 (60) 90 (14) * 148 (22) 41 (6.5) 30 (4.4) 357 (56) 450 (66) 433 (68) 369 (54) 266 (42) 129 (19) 573 (91) 643 (94) 65 (10) 71 (10) 350 (55) 329 (48) a Numbers in parentheses are percentages. ccs = Canadian Cardiovascular Society; artery (13) 207 (84) 56 (23) 134 (55) 54 (22) 8 (3.3) 180 (73) 139 (57) 33 (13) 229 (93) 18 (7.3) 100 (41) IMA = internal mammary Table 2. Cardiac Catheterization Data" Variable Vein Grafts Unilateral Bilateral Only IMA Grafts IMA Grafts (n = 633) (n = 687) (n = 246) Extent of disease One vessel 50 (7.9) 45 (6.6) Two vessels 113 (17.9) 147 (21.4) Three vessels 353 (55.8) 412 (60.0) Left main coronary artery 117 (18.5) 83 (12.1) Left ventricular wall motion score (CASS)b (21.0) 194 (32.1) (28.5) 204 (33.8) (28.9) 149 (24.7) (21.6) 57 (9.4) Mean score ? 4.1 a Numbers in parentheses are percentages. for all patients. CASS = Coronary Artery Surgery Study; artery (15.0) 169 (68.7) 40 (16.3) 68 (29.6) 83 (36.1) 65 (28.3) 14 (6.1) 9.1 t 3.8 Data were not available IMA = internal mammary and musculophrenic branches to their origin. Low-current electrocoagulation was used to mobilize the pedicle, and clips were applied to the larger intercostal branches. The distal anastomoses were performed first after administration of a cold crystalloid oxygenated cardioplegic solution (septa1 temperature, 10" to 12 C) with additional infusions every 20 to 30 minutes. Anastomoses of the VGs or, on occasion, the IMA grafts to the aorta were performed after release of the aortic clamp while the patients were rewarmed to 34 C (rectal or bladder temperature). The sternal edges were reapproximated with five to seven stainless steel wires, which were tightened by manual twisting. The rectus fascia was closed with interrupted braided Dacron sutures. The subcutaneous tissues were closed with one or two layers of continuous absorbable suture. Intravenous antibiotics were administered preoperatively and were continued for 48 hours postoperatively. The number of patients requiring emergent or urgent operation (within 24 hours of cardiac catheterization), the durations of cardiopulmonary bypass and aortic occlusion, the mean number of arteries grafted, and the number of patients undergoing isolated CABG for the three groups are shown in Table 3. Electrocardiograms were obtained on the first and sixth postoperative days. Serum creatine kinase and lactate dehydrogenase (LDH) levels (total and fractionated) were measured 1, 12, and 24 hours postoperatively. The presence of a new Q wave or a ratio of LDH, to LDH, of 1 or greater was considered indicative of perioperative myocardial infarction. Postoperative low cardiac output was considered present when inotropic support (infusion of dopamine hydrochloride or dobutamine hydrochloride at 5 pg/kg/min or more) was required for more than 24 hours. Stroke was defined as any transient or permanent focal neurological deficit. Sternal infection was considered present in patients in whom sternal instability developed

3 212 KOUCHOUKOS ET AL Ann Thorac Surg 1990;49:21&9 Table 3. Operative Data" Vein Unilateral Bilateral Grafts Only IMA Graft IMA Grafts Variable (n = 633) (n = 687) (n = 246) Emergent or urgent 58 (9.2) 4 (0.6) l(0.4) operation Duration of t t 28 cardiopulmonary bypass (min) Duration of aortic occlusion (min) Mean no. of arteries grafted Isolated CABG 413 (65) 624 (91) 243 (99) a Numbers in parentheses are percentages. CABG = coronary artery bypass grafting; artery. IMA = internal mammary in association with positive wound cultures and in whom a second surgical procedure (incision and drainage, removal of the sternal wires with debridement, and secondary closure) was required. Superficial wound infections responding to conservative treatment, sterile wound dehiscences, and wounds demonstrating delayed healing were classified separately. The patients were also stratified according to surgeon, two different antibiotic regimens (one employed before and one after July 1, 1987), presence or absence of a high-laminar-flow operating room (which became available on June 1, 1987), and duration of hospitalization before CABG. Data Management and Statis tical Analysis All data were compiled and stored in a computerized data bank using an IBM 3270 system and were analyzed with SAS (SAS Institute Inc, Cary, NC) on the Washington University Division of Biostatistics computer system. Continuous data were recorded as the mean * the standard deviation. Univariate analysis with 2 testing for proportions or analysis of variance for means was used to compare the characteristics of the three groups of patients. If test results were significant (p < 0.05), then pairwise comparisons were performed to determine if differences occurred between all pairings of surgical methods [8]. Univariate analysis was also used to assess the effect of 21 categorical variables on the development of sternal infection (Appendix 1). These variables were selected in part from a review of publications relating to sternal wound infection in which a number of variables were evaluated for possible association with this complication [ Multivariate logistic regression was used to select the independent predictors of sternal infection. These analyses were performed using PROC CATMOD (SAS) to obtain maximum likelihood estimates. A p value of less than 0.05 was considered significant. Conditional odds ratios for the significant variables and predicted proportions of patients infected for all possible categories were obtained from the logistic regression [14]. Results Compared with the VG patients, the unilateral and bilateral IMA patients were younger, were more often male, had a lower incidence of previous myocardial infarction, congestive heart failure, and severely depressed left ventricular function (wall motion score, 16 to 30), and had a higher prevalence of obesity and smoking (see Tables 1, 2). The IMA patients underwent fewer emergent, urgent, or combined operative procedures and had a shorter average period of hospitalization before operation than the VG patients (see Tables 1, 3). The number of arteries grafted among the IMA patients was higher (see Table 3). All of these differences were significant ( p < 0.05). The bilateral IMA patients were younger than the unilateral IMA patients, were more often male, and had a higher prevalence of smoking ( p < 0.05) (see Table 1). other significant differences in baseline or operative characteristics were observed between these two groups. Mortality Thirty-day mortality was lower among the IMA patients than among the VG patients (unilateral IMA group, 2.8%; bilateral IMA group, 3.7%; and VG group, 7.9%) (Table 4). The differences between the unilateral IMA and VG groups and between the bilateral IMA and VG groups were significant ( p = 0.001). Sixty-two of the 78 postoperative deaths were of cardiac origin. Only 1 of the postoperative deaths was directly attributable to the development of a sternal wound infection. Table 4. Mortality and Morbidity" Variable 30-day mortality Perioperative myocardial infarction Low cardiac output Intraaortic balloon Pump Reoperation for bleeding Transfusion requirements blood products Mean no. of units/ patient Stroke Mechanical ventilation >48 h Pneumonia Sternal infection Superficial chest wound infection, sterile dehiscence, or delayed healing Vein Grafts Unilateral Bilateral Only IMA Graft IMA Grafts (n = 633) (n = 687) (n = 246) 50 (7.9) 5 (0.8) 41 (6.5) 77 (12.2) 23 (3.6) 99 (15.6) (4.6) 90 (14.2) 38 (6.0) 8 (1.3) 14 (2.2) a Numbers in parentheses are percentages. IMA = internal mammary artery. 19 (2.8) 14 (2.0) 30 (4.4) 22 (3.2) 32 (4.7) 213 (31.0) (2.0) 36 (5.2) 17 (2.5) 13 (1.9) 20 (2.9) 9 (3.7) 5 (2.0) 8 (3.3) 11 (4.5) 13 (5.3) 103 (41.9) (0.8) 21 (8.5) 11 (4.5) 17 (6.9) 25 (10.2)

4 Ann Thorac Surg 1990;49:210-9 KOUCHOUKOS ET AL 213 Table 5. Predictors of Sternal Infection by Multivariate Analysis With Logistic Regression Degrees of P Variable Freedom X2 Value Odds Ratio ~~~~ ~ Bypass procedure Obesity index 230 kg/m2 Mechanical ventilation >48 h IMA = internal mammary artery IMA vs veins IMAs vs veins IMAs vs 1 IMA Morbidity significant differences in the incidence of perioperative myocardial infarction, low cardiac output, and reoperation for bleeding were observed among the three groups (see Table 4). The need for postoperative intraaortic balloon pumping, transfusion of blood products, and prolonged mechanical ventilation was significantly greater among the VG patients than either the unilateral or bilateral IMA patients (p < 0.01). The incidence of stroke was higher in the VG group than the bilateral IMA group (p < 0.01), and the incidence of postoperative pneumonia was higher among the VG patients than among the unilateral IMA patients (p = 0.05). ne of the other differences between groups for these events were significant. Sternal infections occurred with greater frequency among the bilateral IMA patients (6.9%) than among the unilateral IMA (1.9%) or VG (1.3%) patients (Fig 1; see Table 4). The differences between the bilateral IMA and unilateral IMA groups and between the bilateral IMA and VG groups were significant ( p < 0.001). Among the 413 VG patients having isolated CABG and the 220 VG patients having combined procedures, the incidence of sternal infection was 1.0% (4 patients) and 1.8% (4 patients), respectively (p = 0.4). The prevalence of sternal infection was significantly higher in diabetic patients overall (3.8% versus 2.0%; p = 0.04) (Appendix 2) and among diabetic patients receiving IMA grafts (bilateral IMA group, 12.5% versus 5.3% [ p = 0.061; unilateral IMA % 81 I (N:633) (N=687) (Nz246) -p=.ooo1- p= i Fig 1. Incidence of sternal infection according to type of bypass graft. (IMA = internal mammary artery.) group, 4.0% versus 1.2% [ p = 0.021; and VG group, 0.6% versus 1.5% [ p = 0.41). By univariate analysis, obesity index of 30 kg/m2 or greater, diabetes, bilateral IMA grafting, and prolonged mechanical ventilation were associated with a significantly higher incidence of sternal infection ( p < 0.05). The increased incidence of infection in patients requiring reoperation for bleeding approached significance (p = 0.07) (see Appendix 2). In the multivariate analysis, bilateral IMA grafting, obesity index of 30 kg/m2 or greater, and prolonged mechanical ventilation were significant independent predictors associated with the development of sternal infection (Table 5). Logit scores and the predicted proportions of patients infected were computed for the 12 possible categories using the three significant variables (Fig 2; Appendix 3). The group with the lowest predicted risk of infection (0.7%) received VGs only, had an obesity index of less than 30 kg/m2, and did not require prolonged ventilation. The group with the highest predicted risk of infection (32.3%) received bilateral IMA grafts, had an obesity index of 30 kg/m2 or higher, and required prolonged mechanical ventilation. The incidence of superficial chest wound infection, sterile dehiscence, and delayed healing in the aggregate was also significantly higher among the bilateral IMA patients than among the VG and unilateral IMA patients (p < 0.05) (see Table 4). Comment Because of its superior long-term patency and the associated beneficial effect on long-term survival, reoperationfree survival, and need for subsequent hospitalization for cardiac-related events compared with VGs, the IMA is currently the conduit of choice for CABG [ In studies [ that have evaluated the relative effectiveness of IMAs and VGs, the majority of patients received only one IMA graft. It has not been conclusively demonstrated that use of both IMAs provides additional benefit over the use of one IMA. In general, bilateral IMA grafting has been employed selectively [l-3, 18-22]. In studies [2, 3, 20, 211 comparing patients who underwent bilateral IMA grafting with those who received only VGs or in whom unilateral IMA grafting was used, hospital mortality rates were not significantly greater among the bilateral IMA groups. A significantly higher incidence of perioperative myocardial infarction among the bilateral IMA patients compared with patients who received only VGs was reported by

5 214 KOUCHOUKOS ET AL Ann Thorac Surg 1990;49:21&9 Fig 2. Logit curve for the three independent predictors of sternal infection (bypass procedure, obesity index, and prolonged mechanical ventilation). Broken lines represent the standard error. (1IMA = one internal mammay artey; 2IMA = both internal mamma y arteries; VG = vein grafts.) Logit Score 4 91 Bypass Conduif VG Mechanical VenlilaPon (hours) 540 Obesity Index (kgim2) c llma VG VG llma 21MA VG 2lMA 21MA 21MA A0 ~ 4 0 ~ 4 0 A0 540 >40 >40 ;30 z30 <30 2% c % <30 30 Buxton and co-workers [21]. Cosgrove and associates [3] documented a significantly greater incidence of blood transfusion among patients with bilateral IMA grafts compared with patients with unilateral IMA grafts and those with VGs only. In the present study, use of bilateral IMA grafts was not associated with increased 30-day mortality compared with single IMA or venous grafting. Early mortality was similar for the unilateral and bilateral IMA patients and was significantly lower for these two groups than for the VG patients (see Table 4). This lower mortality rate was related in a major way to the criteria used to select patients for IMA grafting. The IMA patients were younger, had less preoperative impairment of left ventricular function, and underwent fewer combined, emergent, or urgent procedures. Similar differences in mortality, also related to differing baseline characteristics and selection criteria, have been reported by Jones [2], Cosgrove [3], and their colleagues. With the exceptions of sternal infection and other chest wound problems, none of the other postoperative complications evaluated occurred with greater frequency among the patients receiving unilateral or bilateral IMA grafts than among the VG patients. The prevalence of sternal wound complications was significantly higher among the bilateral IMA patients than the other two groups. In the multivariate analysis, choice of conduit was the most significant predictor for the development of sternal infection. We evaluated a number of variables that have been reported in previous studies [9-131 to be associated with an increased risk of sternal wound infection. Despite the greater prevalence in the VG group of several variables (female sex [lo], depressed left ventricular function [13], combined procedures [12], postoperative low cardiac output [12], and prolonged ventilatory support [lo, 131) reported to be associated with a higher incidence of sternal wound infection, the overall incidence of this complication was 1.3%, lower than that for either the unilateral or bilateral IMA group, but comparable with that reported in other series [ll, 131. The reported incidence of sternal wound infection in patients receiving bilateral IMA grafts has ranged from 1.6% to 8.5% [l, 9, 18, 19, 211. In the studies in which comparisons of sternal infection rates were made with patients receiving unilateral IMA grafts or VGs, a higher sternal infection rate was uniformly observed among the bilateral IMA patients [3, 9, 21, 231. Comparing a group of bilateral IMA patients with identical numbers of patients who were matched for factors associated with increased operative risk and who received either unilateral IMA grafts or VGs, Cosgrove and associates [3] observed a significantly higher incidence of sternal wound complications among the bilateral IMA patients. In a multivariate analysis that examined four variables (age, sex, diabetic state, and number of IMA grafts) for their association with sternal wound complications, diabetes and advanced age emerged as significant variables. In our study, diabetes was a significant predictor for the development of sternal infection in the univariate but not the multivariate analysis. The strong association between obesity, a significant predictor in the multivariate analysis, and diabetes in our patients may have weakened the predictive value of diabetes. The higher prevalence of sternal infection in all three groups in our series compared with similar groups in the series of Cosgrove [3], Buxton [21], and their co-workers may be related to a greater than twofold higher prevalence of diabetes among the patients in our study and possibly to other differences in patient characteristics and patient management. Other variables, not examined in our study or the study of Cosgrove and colleagues [3], might also have independent predictive value for the development of sternal infection. Devascularization of the sternum as a result of mobilization of one or both IMAs has been postulated as a mechanism for the development of sternal wound infec-

6 Ann Thorac Surg 1990;49:21&9 KOUCHOUKOS ET AL 215 tion after myocardial revascularization. The elegant anatomical studies of the blood supply of the sternum in humans by Arnold [24] and the studies of sternal blood flow after sternotomy and mobilization of the IMAs in baboons by Seyfer and associates [25] indicate that the IMAs are the principal source of blood supply to the sternum, and that mobilization of the IMA significantly reduces blood flow to that half of the sternum. These studies and the clinical studies comparing the prevalence of sternal wound infection in bilateral IMA, unilateral IMA, and VG patients strongly suggest that devascularization of the sternum is an important determinant of the development of sternal wound complications. In our study, the presence of other risk factors (obesity and prolonged mechanical ventilation) also increased the risk for development of sternal infection (see Fig 1; Appendix 3). Increasing weight and obesity have been shown to be significant independent predictors for the development of sternal infection [lo, 261. Prolonged mechanical ventilation has also been shown to be a significant predictor by univariate and multivariate analyses [lo, 131. In the present study, use of bilateral IMA grafts was the strongest predictor for the development of sternal infection among patients having coronary artery bypass procedures (see Table 5). Until the superiority of bilateral over unilateral IMA grafting is clearly demonstrated, we believe that bilateral IMA grafting should continue to be employed selectively. Our analyses suggest that patients with bilateral IMA grafts who are obese and who require prolonged ventilatory support are at increased risk for the development of sternal infection. The estimated risk exceeds 10% in these subgroups (see Appendix 3). Patients who receive only VGs or unilateral IMA grafts are also at increased risk (>7%) if obesity is present and prolonged mechanical ventilation is required. Bilateral IMA grafting should also be used selectively in diabetic patients. Although the mortality for sternal wound infection was not excessive in our study, the increased morbidity, including the need for additional surgical procedures and prolonged hospitalization, does not appear to justify the use of bilateral IMA grafts in high-risk patients unless other conduits are not available. We acknowledge the assistance of Brad Wilson, MA, and Jack D. Baty of the Division of Biostatistics, Washington University School of Medicine, with the statistical analyses and that of Darleen Barnes and Joan Dalton with the preparation of the manuscript. References Galbut DL, Traad EA, Dorman MJ, et al. Twelve-year experience with bilateral internal mammary artery grafts. Ann Thorac Surg 1985;40:26&70. Jones EL, Lattouf 0, Lutz JF, King SB 111. Important anatomical and physiological considerations in performance of complex mammary-coronary artery operations. Ann Thorac Surg 1987;43: Cosgrove DM, Lytle BW, Loop FD, et al. Does bilateral internal mammary artery grafting increase surgical risk? J Thorac Cardiovasc Surg 1988;95: Burton BT, Foster WR. Health implications of obesity: an NIH Consensus Development Conference. J Am Diet Assoc 1985;85: Bray GA. Obesity and the heart. Mod Concepts Cardiovasc Dis 1987;56: Campeau L. Grading of angina pectoris. Circulation 1976; 54: Principal Investigators of CASS and Their Associates. National Heart, Lung, and Blood Institute Coronary Artery Surgery Study (CASS): a multicenter comparison of the effects of randomized medical and surgical treatment of mildly symptomatic patients with coronary artery disease, and a registry of consecutive patients undergoing coronary angiography. Circulation 1981;63(Suppl 1): Marasculio LA, McSweeney M. nparametric and distribution-free methods for the social sciences. Monterey, CA: Brooks/Cole Publishing, 1977; Culliford AT, Cunningham JN Jr, Zeff RH, Isom OW, Teiko P, Spencer FC. Sternal and costochondral infections following open-heart surgery. J Thorac Cardiovasc Surg 1976; 72: Breyer RH, Mills SA, Hudspeth AS, Johnston FR, Cordell AR. A prospective study of sternal wound complications Ann Thorac Surg 1984;37: Sarr MG, Gott VL, Townsend TR. Mediastinal infection after cardiac surgery. Ann Thorac Surg 1984;38: Grossi EA, Culliford AT, Krieger KH, et al. A survey of 77 major infectious complications of median sternotomy: a review of 7,949 consecutive operative procedures. Ann Thorac Surg 1985;40: Newman LS, Szczukowski LC, Bain RP, Perlino CA. Suppurative mediastinitis after open heart surgery. Chest 1988; 94: Goodman LJ. Analyzing qualitative/categorical data: loglinear models and latent-structure analysis. Cambridge, MA Abt Books, Singh RH, Sosa JA, Green GE. Long-term fate of the internal mammary artery and saphenous vein grafts. J Thorac Cardiovasc Surg 1983;86: Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med 1984;314: Okies JE, Page US, Bigelow JC, Krause AH, Salomon NW. The left internal mammary artery: the graft of choice. Circulation 1984;7O(Suppl 1): Barner HB. Double internal mammary-coronary artery by- pass. Arch Surg 1974;109: Lytle BW, Cosgrove DM, Loop FD, Borsh J, Goormastic M, Taylor PC. Perioperative risk of bilateral internal mammary artery grafting: analysis of 500 cases from 1971 to Circulation 1986;74(Suppl 3): Geha AS, Hammond GL, Stephan RN, Kleiger RK, Krone RJ. Long-term outcome of revascularization of the anterior coronary arteries with crossed double internal mammary versus saphenous vein grafts. Surgery 1987;102: Buxton BF, Tatoulis J, McNeil JJ, Fuller JA. Internal mammary artery grafting: is this a benign procedure? J Cardiovasc Surg (Torino) 1988;29: Henze A, Ramstrom J, Nystrom SO. Bilateral internal mammary artery for coronary revascularization. Scand J Thorac Cardiovasc Surg 1989;23:9-12. Grmoljez PF, Barner HB. Bilateral internal mammary artery mobilization and sternal healing. Angiology 1978;29:2724. Arnold M. The surgical anatomy of sternal blood supply. J Thorac Cardiovasc Surg 1972;64: Seyfer AE, Shriver CD, Miller TR, Graeber GM. Sternal blood flow after median sternotomy and mobilization of the internal mammary arteries. Surgery 1988;104: Nagachinta T, Stephens M, Reitz B, Polk BF. Risk factors for surgical-wound infection following cardiac surgery. J Infect Dis 1987;156:

7 216 KOUCHOUKOS ET AL Ann Thorac Surg 1990;49:210-9 Appendix 1. Variables Tested for Association With Sternal Infection Preoperative Clinical Variables Age <65 yr 265 yr Sex Diabetes Chronic obstructive pulmonary disease Obesity index <30 kglm' 230 kglm' Previous cardiac operation Left main coronary artery disease Left ventricular wall motion score Length of hospitalization before CABG 52 days >2 days Operation-Related Variables Surgeon Emergent or urgent operations Type of operation Isolated CABG Combined procedure Bypass procedure Vein grafts only Unilateral IMA grafting Bilateral IMA grafting Duration of cardiopulmonary bypass 413 min 2113 min Laminar-flow operating room Postoperative Variables Reoperation for bleeding Blood transfusion Low cardiac output Mechanical ventilation 548 h >48 h Pneumonia Antibiotic regimen Appendix 2. Predictors of Sternal Infection by Univariate Analysis. of Sternal Infections1 Variable Total Patients 70 p Value Overall Age <65 yr 265 yr Sex Male Female Diabetes Chronic obstructive pulmonary disease Obesity index <30 kglm' 230 kglm' Previous cardiac operation Left main coronary disease Left ventricular wall motion score Preoperative hospital stay 52 days >2 days Surgeon A B Emergentlurgent operation Type of operation Isolated CABG Combined procedure Bypass procedure Vein grafts only Unilateral IMA Bilateral IMA Duration of cardiopulmonary bypass 413 min 2113 min Laminar-flow operating room Reoperation for bleeding Blood transfusion 3811, / , ,487 4/79 22/1, , , / /1, /1, , , , <

8 Ann Thorac Surg 1990;49:21&9 KOUCHOUKOS ET AL 217 Appendix 2. Continued Variable. of Sternal Infections1 Total Patients % p Value Low cardiac output 33/1, Mechanical ventilation 548 h 2911, >48 h Pneumonia 35/1, Antibiotic regimen A 33/1, B CABG = coronary artery bypass grafting; artery. IMA = internal mammary Appendix 3. Logit Scores and Predicted Sternal Infection Rates for Patient Groups Using the Three Independently Predictive Variables Mechanical Obesity Predicted Bypass Ventilation Index Logit Proportion Standard Conduit (h) (kglm ) Score Infected Error Veins 1 IMA Veins Veins 1 IMA 2 IMAs 1 IMA Veins 2 IMAs 1 IMA 2 IMAs 2 IMAs 548 < < >48 < < >48 < > > >48 < > IMA = internal mammary artery DISCUSSION DR ALEXANDER S. GEHA (Cleveland, OH): Our own experience with the double internal mammary artery is pretty much in line with that of Kouchoukos and associates, as far as the early risks and complications. Although our series has a smaller number of patients with bilateral IMA grafts, the use of the double IMA appears to add to the risks of sternal complications in these patients. I want to mention some of the results that we have encountered over the long term with the use of the double IMA, predominantly grafting the left IMA to the left anterior descending coronary artery and the right IMA to either the diagonal or circumflex coronary artery, and oftentimes passing the right IMA in the transverse sinus behind the pulmonary artery and the aorta. In the early days of our experience with coronary bypass grafting between 1973 and 1978, we had considerable enthusiasm for the use of the left IMA and enthusiasm for using both IMAs for crossed double IMA grafting in select patients who were predominantly male and younger, somewhat similar to those in the St. Louis University series of Dr Fiore and associates [l]. We therefore took advantage of a long-term follow-up, and in 1987 reviewed the results over 10 years in these patients and tried to match them with a series of patients who had similar demographic and clinical characteristics, and who had only vein grafts instead of double IMA grafts placed into similar coronary vessels during that same historical period. Over 10 years of follow-up, the linearized incidence of events shows considerably fewer cardiac-related deaths, reoperations, recurrent angina, and myocardial infarctions in the group who received the double IMA versus veins only. Mind you, we did not compare the double mammary group with another having a single left IMA graft to the left anterior descending coronary artery and a vein graft to another vessel. The actuarial curves also show significantly greater freedom from cardiac death, from myocardial infarction, from recurrent angina, and from reoperation for the group who received those crossed double IMA grafts instead of the group who received veins only. Dr Kouchoukos has very appropriately pointed out that his group of patients with double IMA grafts was younger, had a male predominance and a lower incidence of myocardial infarction, congestive heart failure, and decreased ejection fraction, and had fewer emergent operations and fewer urgent operations or combined operations than his group with vein grafts only. I think this is the key because the selection of patients who receive double IMA grafts at this time is, as he pointed out, very crucial. We still are debating even the early risks of the operation. We heard in the report by Loop and associates [2] that the use of the double IMA graft was not in itself, without the presence of diabetes, a predictor of sternal wound complications. The paper by Kouchoukos and associates suggests a different conclusion. The long-term results also are not all in, and therefore I want to sound a note of caution that the use of the right IMA, especially as a natural pedicle to graft very distal vessels, should be done with utmost care in select patients by those who have experience with it. Its indiscriminate use, I am afraid, may lead sometimes to disastrous operative results if one overextends its use in an attempt to achieve a long-term benefit. DR JOHN E. ANDERSON (Boston, MA): I would like to present the experience of a single surgeon extending over 24 months involving 133 patients. This is a smaller series and represents the experience of a surgeon not receiving training in mammary artery grafting during his residency training program. Of the total patients, 238 received coronary revascularization; 56% of these patients received bilateral internal mammary artery grafts. The 238 patients receiving coronary revascularization represents approximately half of this surgeon s surgical experience, the other half consisting of isolated valve operations and congenital cardiac operations. The surgical policy has been to find a reason not to do bilateral mammary revascularization instead of finding a reason to do it. In this series of 133 patients, 80% were male, 20% had an ejection fraction ranging from 20% to 40%, and 26% of the series were diabetics. The age range indicates that the majority of patients were in either their sixth or seventh decade of life. At the time of operation, the majority of patients (61%) received one mammary artery graft to one coronary artery. As experience has progressed with this technique, there has been a trend toward bilateral sequential revascularization, which is 28% of this series. When extra mammary artery is available, sutured Y

9 218 KOUCHOUKOS ET AL Ann Thorac Surg 1990;49:21&9 grafts are established to increase the number of coronary arteries revascularized with mammary conduit. Operative strategy for mammary revascularization included use of a 2 to 6-cm patch arterioplasty of mammary artery in 27% of this series. This was primarily for midsegment stenosis in the left anterior descending coronary artery. A free mammary artery graft was used in 15% of this series and endarterectomy of the revascularized coronary artery was required in 11% of this series. operative or hospital mortality has been incurred in this series. Reoperation for bleeding was required in 4 patients (3.8%) early in this experience. Perioperative neurological insult occurred in 3 patients, all of whom recovered. Two patients (1.5%) incurred a perioperative myocardial infarction. With respect to sternal wound complications, the results are similar to those of the series of Kouchoukos and associates. Early infection developed in 4.5% of the patients. Dehiscence without infection developed in 1 patient, late sternal osteomyelitis developed in 1 patient 3 months after operation, and a late dehischence of the sternotomy incision developed in 1 patient more than 6 months after operation. In evaluating this small series, factors that were found not to be related to infection or sternal complication rate were (1) body mass to height ratio (I believe we will have to reevaluate our data in a more sophisticated way as Kouchoukos and associates have done); (2) length of postoperative ventilation (107 of 133 patients or 80% were extubated from ventilatory support on the first postoperative day; therefore our numbers were too small to show a relation to wound infection risk); (3) cross-clamp time; (4) perfusion time; (5) operating time; and (6) reoperation for bleeding. The two factors in this series that were related to the risk of wound infection were diabetes and age greater than 70 years. Dr Kouchoukos, is what is your attitude currently toward revascularization in insulin-dependent diabetics who are not obese and elderly? Also, could the benefit of bilateral IMA revascularization over single IMA revascularization be more quickly shown in patients operated on in their seventh decade of life? DR ALFRED T. CULLIFORD (New York, NY): During this meeting six papers have addressed various ramifications of IMA grafting. This unprecedented amount of attention has focused on operative mortality, recurrent angina, survival, freedom from infarction, old age, and the varying results obtained with bilateral IMA implants. After 2% decades of clinical experience and considerable discussion, the IMA remains the conduit of choice for many of us here. Dr Kouchoukos and associates have observed an increase in infection rate when bilateral mammary arteries are employed and identified several risk factors responsible for this increase. This association has been studied in detail at New York University. In 1976 we noted an infection rate of 8.5% when bilateral IMA grafts were employed and were both pleased and relieved to note that it decreased to just under 4% when 135 recent patients with bilateral implants were reviewed. An important study was conducted by Dr Arnold in 1972 concerning sternal blood supply. The blood supply to the sternum rises from a periostial arcade arising from the internal mammary artery. This was visualized by Dr Arnold in a laboratory preparation after injecting the mammary vessel; rich arborizing branches could be seen arising from both mammary arteries. When, however, another laboratory preparation was made in which both mammary arteries were mobilized, these arcades filled very poorly, suggesting the possibility that relative sternal ischemia may occur. With this in mind it is easy to understand why factors such as diabetes, obesity, low cardiac output, and prolonged ventilatory support were identified by Kouchoukos and associates as impor- tant risk factors. The decision to employ both IMAs then becomes a formulation of a riskhenefit ratio. If too many risk factors are present, the benefit declines and the price for this decision is paid for by the patient in terms of morbidity and mortality. With this in mind I have two questions. In which patients would you continue to use bilateral IMA grafts? Would age alone exclude someone or would the presence of one, two, or three risk factors exclude someone? Finally, in the medical-legal age, should we emphasize these increased risks to our patients as part of an informed consent? DR NOEL L. MILLS (New Orleans, LA): In analyzing these reports, it becomes apparent that there is a real difference in the statistics between those of the group in Miami [3] and those by Dr Kouchoukos group. When one looks at these reports one finds that the group from Miami took the IMA down skeletonized as a single vessel as opposed to a pedicle, which obviously is more damaging to tissues and collateral circulation. It may be that in diabetics-and both of those papers had comparable groups of diabetics, 20% to 25%-we should at least take one IMA down as a skeletonized vessel. I would like to also point out that it behooves us to know the crest factor of our individual electrosurgical units. Ten to 11 is optimal to avoid tissue destruction. DR RICHARD K. HUGHES (Los Angeles, CA): Just in case everybody is going to go home and do bilateral IMA grafts, it is my understanding that, at least in some institutions, there is concern about bringing the right IMA over to the front of the left side of the heart because of the risk of possible injury at reoperation. In younger patients, bringing the right IMA across in front of the heart may subject a patient to risk if reoperation is necessary. I would like to have Dr Kouchoukos comment on this point. DR KOUCHOUKOS: Dr Geha has presented important information on the long-term results of bilateral IMA grafting. As I recall, that study excluded hospital mortality from the actuarial analysis of survival. The results must therefore be interpreted with this in mind and appear similar to those presented earlier by Dr Fiore [l]. I appreciate Dr Anderson s comments. His results are similar to those that we presented. As a result of our analyses, we have adopted a more conservative view toward bilateral IMA grafting. We currently do not perform the procedure in obese, diabetic patients or in patients over the age of 70 years unless other suitable conduits are unavailable. We will continue this policy until data become available that demonstrate a greater benefit of bilateral over unilateral IMA grafting. We believe that bilateral IMA grafting may have a beneficial effect in young patients, especially those with elevated cholesterol and triglyceride levels, and continue to use it in this subset, even in the presence of diabetes and obesity, recognizing that there may be an increased incidence of sternal wound complications. It is important, as Dr Culliford pointed out, that this increased risk be explained to the patient before operation. Dr Mills, 1 do not have any information about the possible beneficial effect of skeletonization of the IMA. Dr Culliford showed us some of the results of the elegant study of Dr Arnold that indicate that interruption of the major branches of the IMA results in devascularization of the sternum and appears to be an important factor for the development of sternal wound complications, particularly if other risk factors for infection are present. Dr Hughes, we use the right IMA as a pedicle graft in about half the cases of bilateral IMA grafting, and almost always anastornose it to the anterior descending coronary artery. In the remaining cases it is used as a free graft to the anterior descend-

10 Ann Thorac Surg 1990;4921&9 KOUCHOUKOS ET AL 219 ing or circumflex systems. We rarely attach it to the right coronary artery. We too are concerned about the risk of injury to the artery at reoperation, but to date this has not occurred. A major point we wish to make is that if bilateral IMA grafting is applied to patients with other risk factors for infection, the rate of sternal infection will be substantially increased. Because of the increased mortality, morbidity, and cost associated with sternal wound infection, and the lack of evidence that bilateral IMA grafting has a beneficial effect on long-term survival, use of this procedure in high-risk patients is not advisable unless no other suitable conduits are available. References 1. Fiore AC, Naunheim KS, Dean P, et al. Results of internal thoracic artery grafting over 15 years: single versus double grafts, Ann Thorac Surg 1990;49: Loop FD, Lytle BW, Cosgrove DM, et al, Sternal wound comp~ications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care, Thorac Surg 1990;49: , Galbut DL, Traad EA, D~~~~~ MJ, et al, Seventeen-year experience with bilateral internal mammary artery grafts. Ann Thorac Surg 1990;49: