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Ann Thorac Surg 1996;62:63-69
© 1996 The Society of Thoracic Surgeons
Miami Heart Institute, Miami Beach, Florida
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Abstract |
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 TopFootnotes Abstract IntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Methods. A retrospective analysis was conducted to identify risk factors that adversely influence hospital mortality, morbidity, and long-term clinical results in women undergoing bilateral internal mammary artery grafting. From January 1972 through October 1994, 327 consecutive women received bilateral internal mammary artery grafts and supplemental vein grafts. Patient age ranged from 32 to 84 years (mean, 65.7 years). There were 262 patients (80.1%) with three-vessel disease; 71 (21.7%) had substantial (>50%) stenosis of the left main coronary artery, 65 (19.9%) had a moderately reduced (0.30 to 0.50) ejection fraction, and 11 (3.4%) had a severely reduced (<0.30) ejection fraction. Preoperatively, 316 patients (96.6%) were in New York Heart Association class III or IV.
Results. There were 1,016 coronary artery grafts (mean, 3.1 per patient). The overall hospital mortality rate was 3.4% (11 of 327). Postoperative complications included myocardial infarction in 18 patients (5.5%), stroke in 5 (1.5%), pulmonary insufficiency in 11 (3.4%), reoperation for bleeding in 7 (2.1%), and sternal infection in 8 (2.4%). Independent predictors of operative death were postoperative cardiac arrest (p < 0.001), use of intraaortic balloon pump (p < 0.001), and reoperation for bleeding (p < 0.050). Follow-up was completed on 316 hospital survivors (100%) and ranged from 6 months to 21 years (mean, 5.1 years). Actuarial survival (mean ± standard error of the mean) was 90.5% ± 1.9% at 5 years and 65.6% ± 6.1% at 10 years. At follow-up, 252 patients (94.0%) were asymptomatic in New York Heart Association class I, and 12 (4.5%) were in class II.
Conclusions. This longitudinal study demonstrates that bilateral internal mammary artery grafting, though technically demanding, can be achieved in women with low hospital mortality and morbidity rates. Patients experienced reduced late cardiac events, excellent functional improvement, and enhanced long-term survival.
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Introduction |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Coronary bypass grafting remains the most widely accepted form of myocardial revascularization for patients with extensive disease. However, the overwhelming majority of procedures are performed on men. There is increasing evidence that women have not received the benefits of intensive and invasive evaluation and treatment at the same rate as men [2, 3]. These sex differences have influenced the course of operative treatment of coronary artery disease in women [4].
It is well documented that coronary operations carry a higher mortality rate in women than in men [4–7]. This has been attributed to a series of risk factors, such as the incidence of diabetes [5, 8], smaller body habitus [4, 6, 7], coronary artery size [4], and preoperative functional status [9, 10]. Moreover, a number of studies have shown a diminished long-term survival and clinical status [5, 7,11–13].
The internal mammary artery has become the conduit of choice for coronary bypass grafting. Early and long-term patency rates are superior to those with saphenous vein grafts [14]. Patient survival and freedom from reoperation and late cardiac events are also clearly improved. Studies have demonstrated the internal mammary artery's resistance to atherosclerosis and intimal hyperplasia [15] as well as the ability to autoregulate and supply sufficient flow to the myocardium [16]. The use of bilateral internal mammary artery (BIMA) grafting has clearly demonstrated viability for early and long-term patency and has emerged as the alternative of choice for myocardial revascularization [17].
Despite the extensive use of BIMA grafting, its application in women has not been well established. Its impact on operative mortality and morbidity as well as on long-term survival and improved clinical status also has not been defined clearly in this patient group. The purpose of this report is to discern the efficacy of BIMA grafting in women and to assess potential operative risk factors that may adversely influence hospital mortality, morbidity, and long-term clinical results.
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Patients and Methods |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Coronary risk factors in the series included hypertension (diastolic blood pressure >90 mm Hg) in 136 patients (41.6%), hyperlipidemia (cholesterol level >200 mg/dL) in 57 patients (17.4%), diabetes mellitus (insulin-dependent and noninsulin-dependent) in 89 patients (27.2%), history of smoking in 147 patients (45.0%), and renal dysfunction (creatinine level 
2.0 mg/dL) in 5 patients (1.5%).
One hundred forty-five patients (44.3%) had experienced at least one myocardial infarction before operation. Forty-two patients (12.8%) had a history of a recent myocardial infarction (<3 weeks) and 95 (29.1%) had had a remote myocardial infarction (>3 weeks). In 19 patients (5.8%), the timing of the myocardial infarction was not documented. There were 36 patients (11.0%) who had a history of congestive heart failure.
Unstable angina was present in 237 patients (72.5%) and chronic stable angina in 75 patients (22.9%); in 3 patients (0.9%), the type of preoperative angina was unknown. Preoperative functional class was ranked according to the New York Heart Association (NYHA) classification system. Eleven patients (3.4%) were in class II, 144 (44.0%) in class III, and 172 (52.6%) in class IV. Thirty-three patients (10.1%) had previously undergone percutaneous transluminal coronary angioplasty, and 15 patients (4.6%) had had a coronary bypass operation.
Preoperative Angiographic Findings
Selected coronary arteriography was performed on all patients before operation, with specific indices carefully reviewed. Severe coronary artery disease in the present study was defined as an estimated reduction in luminal diameter of 50% or more. Preoperative angiography demonstrated triple-vessel disease in 262 patients (80.1%), double-vessel disease in 60 patients (18.3%), and single-vessel disease in 5 patients (1.5%). Left main coronary artery disease (stenosis >50%) was documented in 71 patients (21.7%).
Dominant right coronary artery circulation was observed in 292 patients (89.3%) and dominant left in 24 patients (7.3%). Balanced circulation was demonstrated angiographically in 11 patients (3.4%). Ejection fraction from left ventriculography was available in 323 patients (98.8%). The ejection fraction was greater than 0.50 in 247 patients (75.5%), between 0.30 and 0.50 in 65 patients (19.9%), and less than 0.30 in 11 patients (3.4%). The ejection fraction was unavailable in 4 patients (1.2%). The clinical characteristics of the patient population are summarized in Table 1
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Operative Technique
Details of the operative technique applied in the current series, including internal mammary artery mobilization, orientation, and anastomotic construction in BIMA grafting, have been discussed previously [17]. The internal mammary artery is dissected as an isolated pedicle from the chest wall, free from surrounding muscle and fascia. The vein is initially dissected, but subsequently removed to allow maximal length and versatility. All side branches are then cauterized carefully and clipped as necessary. Since 1989, combined antegrade and retrograde infusion methods of cardioplegia have been implemented to enhance myocardial protection during the operation.
Operative Data
The type of conduit and corresponding recipient arteries are presented in Table 2. A total of 1,016 coronary artery grafts were performed (mean, 3.1 per patient; range, 2 to 6). Each patient received BIMA grafts, and in 234 patients (71.0%) an additional 303 grafts were constructed with autologous vein. Five left and 22 right internal mammary artery conduits were used as free grafts. There were 92 sequential grafts in the series. The mean cardiopulmonary bypass time was 110.5 ± 43.6 minutes (range, 40 to 351 minutes). The mean aortic cross-clamping time was 66.9 ± 21.1 minutes (range, 20 to 200 minutes).
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A Patient Registration Form and a Patient Follow-Up Form were completed for each participant in the study. These data collection instruments provided standardized reporting of each patient's clinical status before and after the operation. Data were entered into the Patient Analysis and Tracking Systems (PATS; Axis Clinical Software, Inc., Portland, OR). A 100% follow-up was obtained.
Statistical Analysis
Data are presented as frequency distributions and simple percentages. Values of continuous variables are expressed as mean ± standard deviation. Univariate analysis of selected preoperative and postoperative discrete variables was accomplished by 
2 analysis, the continuity-adjusted 2 analysis, or a two-tailed Fisher's exact test with the appropriate degrees of freedom. A stepwise multivariate logistic regression of preoperative and postoperative variables achieving statistical significance (p < 0.05) was performed in a forward fashion to identify potential predictors of hospital death. A significance level of p 
0.05 was required for variables to be entered into the model.
Patient survival was expressed by actuarial analysis according to the method of Cutler and Ederer [18] using time zero as the date of operation and death as the end point and by linearized occurrence rates. Data collected were subjected to both quantitative and qualitative analysis using Statistical Package for the Social Sciences (SPSS/PC+ 5.0). A significant difference between measurements was defined as p less than or equal to 0.05.
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Results |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Patients with sternal infections included those with instability of the sternum with positive wound cultures necessitating an additional surgical procedure, such as incision and drainage, debridement, or secondary closure. Respiratory insufficiency included patients who required intubation for more than 48 hours or tracheostomy (or both). Cerebrovascular accident referred to a focal neurologic deficit that remained unresolved and persisted for more than 24 hours, and renal dysfunction was defined as a creatinine level greater than or equal to 2.0 mg/dL.
Myocardial infarction was defined as a new onset of Q waves with or without elevation of myocardial enzymes, or a substantial elevation of myocardial enzymes alone. Low cardiac output referred to clinical evidence of hypotension, oliguria, and peripheral vascular constriction with normal or supranormal left ventricular filling pressure or a measured cardiac index of less than 2 L • min-1 • m-2, necessitating the administration of catecholamines or use of the intraaortic balloon pump, or both.
Placement of the intraaortic balloon pump was required in 44 patients (13.5%). Nineteen patients (5.8%) had an intraaortic balloon pump placed preoperatively, 20 (6.1%) intraoperatively, and 5 (1.5%) postoperatively. None of the patients requiring use of the intraaortic balloon pump experienced a major complication. The overall incidence of postoperative morbidity in the series was low, with most patients (n = 261; 79.8%) experiencing no hospital complications. The average postoperative length of stay was 13.3 ± 11.0 days.
Hospital Mortality
Hospital mortality was defined as death occurring during the operation or during the hospitalization in which the procedure was performed. Death occurring after discharge from the hospital but within 30 days of the surgical procedure was counted as a hospital death unless the cause was unrelated to the operation. The overall hospital mortality rate for the series was 3.4% (11 of 327). The elective mortality rate was 2.4% (3 of 125), the urgent mortality rate was 3.7% (7 of 191), and the emergent mortality rate was 9.1% (1 of 11). Within-group comparison of the mortality rates for various urgency categories did not achieve statistical significance.
Univariate analyses were conducted using bivariable contingency tables for 27 potential perioperative risk factors to explore their relation to hospital mortality. There were 18 preoperative and 9 postoperative variables. For statistical analysis, patients in NYHA class II and III were combined as one subgroup versus class IV. Further, patients with ejection fraction less than 0.30 were combined as one subgroup, and those with ejection fraction of 0.30 and greater in another.
Table 3 lists those variables associated with hospital mortality that achieved statistical significance (p < 0.05). Variables found to be significant in the univariate analyses were then entered into a stepwise logistic regression to identify a configuration of independent predictors of mortality in a multivariate model.
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. At 5 years, survival (mean ± standard error of the mean) was 90.5% ± 1.9%, and at 10 years it was 65.6% ± 6.1%.
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. All patients in the series improved at least one class, except for 2 patients who remained in class IV and 1 patient in class II. Preoperatively, 96.6% were in either class III or IV; on completion of the present follow-up, 98.5% were in class I or II. These results are impressive and demonstrate an overall enhanced level of functional improvement in this patient group.
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Comment |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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The focus of the present study was to assess the impact of BIMA grafting on operative and long-term results in a group of 327 consecutive female patients. This cohort was composed of a subgroup of 1,198 women who underwent coronary bypass grafting in a single practice between 1972 and 1994. Patient age ranged from 32 to 84 years, with a mean of 65.7 years. The majority of patients (65.7%; 215 of 327) were 65 years of age or older. Several authors have reported an increased operative mortality rate in women undergoing coronary artery bypass grafting over the age of 65 [22, 23]. Others have expressed some reluctance in operating on patients over the age of 70 [24]. Despite these findings, advanced age (65 years and older) was not a significant risk factor for operative death in the present study.
The vast majority of patients in this study were severely symptomatic: 96.7% were in NYHA class III or IV and 72.5% had an unstable anginal syndrome preoperatively. These findings are consistent with the extensive experience of the CASS Study [4], the Cleveland Clinic [14], and others [8–10, 12, 20]. In this study, the incidence of triple-vessel disease (80.2%) was greater than previously reported [4, 5, 11, 12, 14]. The number of grafts per patient (mean, 3.1) was also higher.
Despite the extent of coronary artery disease in this patient population and the relatively high incidence of previous myocardial infarction (44.3%; 145 of 327), the vast majority of patients had preserved (greater than 0.50) left ventricular ejection fraction (75.5%; 247 of 327). This finding is in agreement with previous reports [14, 20].
The operative mortality rate in the present series was 3.4%, which is consistent with other reports [17]. Over the past 5 years, the mortality rate in the present series has decreased to 0.9%, while the demographics of the population have remained constant. These results may be attributed to advances in myocardial preservation, anesthesia management, and an aggressive postoperative care program.
Urgency of the operation has been reported to influence operative outcome adversely in both men and women [7, 19, 23]. However, in the present study, urgency was not found to increase the risk for operative mortality. Though a trend exists-with the operative mortality rate being 2.4%, 3.7%, and 9.1%, respectively, for elective, urgent, and emergent cases-these differences did not achieve statistical significance.
Reoperations are done in an ever-increasing number of patients undergoing myocardial revascularization. Operative history has been described as a risk factor for operative mortality [13, 21]. Therefore, BIMA grafting can be a viable alternative for patients whose saphenous vein has been harvested previously. In the present study, operative mortality was not significantly higher in reoperated patients (2.9% versus 13.3%; p = 0.085). These results must be interpreted with caution because only a limited number of patients in the series underwent reoperation.
Univariate analysis of 18 preoperative variables revealed that previous myocardial infarction, NYHA class IV, and reduced left ventricular ejection fraction (less than 0.30) were significant predictors of hospital mortality. Each of these factors has been described to be present in coronary bypass patients [8, 9, 12, 13, 21–23]. Their specific role in internal mammary artery grafting requires further evaluation. An analysis of comparative risk factors in a matched set of men and women with BIMA grafting may clarify this issue. None of these preoperative factors in the present study proved to be significant predictors in a multivariate model. Although these factors may serve as markers of less than favorable outcome, it is not clear whether this is due to an increased risk associated with any revascularization procedure or specifically associated with BIMA grafting. This issue should be explored further by examining the relative risk profiles of women with bilateral and single internal mammary artery grafting.
Multivariate analysis in the present study disclosed postoperative cardiac arrest, use of the intraaortic balloon pump, and reoperation for bleeding as independent predictors of operative mortality. Eleven of 327 patients (3.4%) suffered a postoperative in-hospital cardiac arrest. Only 45.5% (5 of 11) of these patients survived the event. This finding corroborates our experience in men with BIMA grafting, but not in women with single internal mammary artery grafting. This occurrence appears to be related more to technique than to gender. This tendency has been described previously and is more likely associated with the specific requirements of postoperative care in BIMA patients [25]. Initially, internal mammary artery grafts supply a reduced flow rate when compared with saphenous vein grafts, which may result in myocardial ischemia [26, 27]. As a result, BIMA patients are more vulnerable to postoperative hypotension or low cardiac output. Therefore, care must be exercised with BIMA grafting in patients with impaired hemodynamic indices, ventricular hypertrophy, or active unstable ischemia.
This factor may also account for the substantial use of the intraaortic balloon pump and its association with hospital mortality. The absence of vascular complications in the present series does not discourage use of the intraaortic balloon pump, but rather clearly defines a subset of patients with preoperative, intraoperative, or postoperative ventricular dysfunction or severe ischemia.
Although reoperation for bleeding has been noted to carry an increased risk of operative mortality [28], this has not been a universal finding. In fact, this was not a predictor of operative mortality in univariate analysis of a computer-matched cohort from the same data base of women with single internal mammary artery grafting. In our experience, BIMA patients seem more susceptible to impairment in cardiac function and oxygen delivery factors associated with severe postoperative bleeding.
The incidence of sternal wound infection has been reported to be higher in patients who receive BIMA grafts [22]. However, this has not been a consistent finding [17]. Gender, diabetes, and advanced age have been reported to be significant risk factors for sternal wound infection in BIMA patients [29]. In this series, the incidence of sternal infection was higher both in diabetics and in patients 65 years of age and older. However, neither variable achieved statistical significance. Although it is possible that these trends may achieve statistical significance in a larger group of patients, this study contains 33% more patients than in a previous report, in which the incidence of sternal infection was approximately three times higher (2.4% versus 6.9%) [29]. The relatively low incidence of sternal infection in this series, as well as in others, may be related to the operative technique used to dissect the isolated internal mammary artery, free of a large thoracic wall pedicle [17]. This operative technique also may cause less disruption of the sternal blood supply and lymphatic drainage, as well as provide a longer, more versatile graft.
Numerous studies of female coronary bypass patients have documented both diminished long-term survival and clinical status [5, 7, 11–13]. On the other hand, BIMA grafting has been shown to result in excellent long-term survival, improved freedom from recurrent angina, and reduced need for further intervention [30].
Follow-up data were obtained for all 316 hospital survivors. At the completion of the present follow-up, there were 268 patients (84.4%) alive. The actuarial survival at 5 years was 90.5% ± 1.9% and at 10 years was 65.5% ± 6.1% for the series. These 5- and 10-year survival rates were found to be comparable to those reported previously for women undergoing myocardial revascularization [7, 13].
The long-term clinical impact of BIMA grafting in women in the present study has been impressive. At follow-up, 98.5% of the patients were in NYHA class I or II, whereas 96.6% had been in class III or IV preoperatively. Moreover, 97.5% of patients were free of known subsequent myocardial infarction (0.49% per patient-year); 98.4% were free of percutaneous transluminal coronary angioplasty (0.31% per patient-year); and only 1 patient required reoperation (0.06% per patient-year).
Improved clinical status for patients undergoing BIMA grafting versus single internal mammary artery grafting has been reported previously [30]. The dramatic clinical benefits achieved in this study suggest that the internal mammary artery graft may have a more positive effect on long-term results in women than in men. However, caution must be exercised in its use in cases with severe active ischemia, ventricular hypertrophy, or severe left ventricular dysfunction. The improved long-term patency of the internal mammary artery graft may be even more critical in women and appears to reverse the previously reported diminished long-term benefits. These findings provide increased support for the continued use of BIMA grafting in women.
To assess further the role of the internal mammary artery in coronary bypass grafting, it may be of value to compare computer-matched groups of women with single grafts to those with BIMA grafts. Moreover, studies should compare BIMA grafting in men and women. This will assist in evaluating more completely the effects of single and BIMA grafting and their influence on long-term survival in women as compared with men.
The results of this longitudinal analysis are encouraging and provide substantial evidence that BIMA grafting in women can be accomplished with low hospital mortality and morbidity rates. Further, it has demonstrated a decreased rate of late cardiac events, excellent functional improvement, freedom from recurrent ischemia or reoperation, and enhanced long-term survival in this patient population. The internal mammary artery is clearly the conduit of choice in women undergoing myocardial revascularization. Moreover, it plays a critical role in the operative management of women with coronary artery disease.
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Acknowledgments |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Footnotes |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Address reprint requests to Dr. Kurlansky, Nichol Building Level E, 4701 Meridian Ave, Miami Beach, FL 33140.
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References |
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TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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