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Ann Thorac Surg 2007;83:969-978
© 2007 The Society of Thoracic Surgeons
Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Accepted for publication October 6, 2006.
* Address correspondence to Dr Conte, Division of Cardiac Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD 21287-4618 (Email: jconte{at}csurg.jhmi.jhu.edu).
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Methods: We retrospectively reviewed all patients who underwent AVR-CABG at our institution between January 2000 and December 2004. Patients with any previous or concomitant procedures were excluded. The Kaplan-Meier method was used to calculate survival and freedom from postoperative repeat revascularization. Predictors of mortality were determined by Cox regression analysis.
Results: The study cohort consisted of 233 AVR-CABG patients. Mean follow-up was 2.2 ± 1.7 years with one patient lost to follow-up. Preoperative clinical characteristics were well-matched between patients who received one (n = 86), two (n = 81), or three or four (n = 66) bypass grafts. Operative mortality was 9.3%, 11.1%, and 7.6%, respectively (p = 0.76). Patients in all groups demonstrated significant improvement in New York Heart Association (NYHA) status (p < 0.01). Freedom from postoperative repeat revascularization for all patients after five years was 96.8% and did not differ among groups (p = 0.93). Five-year survival for each group was 63.6%, 72.4%, and 63.9%, respectively (p = 0.91). Emergent operation, ejection fraction less than 0.30, operative age greater than 65 years, NYHA class III/IV, and chronic obstructive pulmonary disease were significant predictors of mortality. The number of stenosed vessels, the number of bypass grafts, incomplete revascularization, and the presence of aortic stenosis or aortic insufficiency did not predict mortality.
Conclusions: For patients undergoing AVR-CABG, the number of bypass grafts does not adversely affect survival. Rather, a patient’s preoperative risk factors are a better predictor of outcome.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Although some studies have analyzed briefly the role of multiple bypass grafts on outcomes [5, 9, 10], we have found no previous study that has specifically investigated the impact of the number of grafts and the completeness of revascularization on outcomes in patients undergoing AVR-CABG in the modern era. We believe that a detailed analysis of this frequently encountered issue is lacking from current AVR-CABG literature. The central issue is whether, or not, taking the time to perform more bypass grafts to achieve a complete revascularization will impact outcomes. We hypothesize that completeness of revascularization and not just the number of bypass grafts is an important factor in successful outcomes after AVR-CABG.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Data collection consisted of review of patient medical records. Follow-up data were collected by review of outpatient records, letter mailings, and telephone interviews. The methods of this study and the Health Insurance Portability and Accountability Act of 1996 waiver for individual patient consent were approved by the Johns Hopkins Institutional Review Board.
Definitions of Variables
All patients received preoperative cardiac catheterization and echocardiography. Coronary arteries with greater than 70% narrowing were considered stenosed. Categorization of the extent of CAD (one-, two-, or three-vessel disease) was based on stenosis of a major artery or one of its branches. Left main coronary disease was considered a two-vessel disease because stenosis in this artery impacts both the left anterior descending (LAD) and left circumflex (LCX) arteries. Revascularization was considered incomplete if a major artery (LAD, LCX, or right coronary artery) or one of its branches had a stenosis of greater than 70% that was not revascularized with a bypass graft at the time of surgery or with either preoperative or postoperative percutaneous interventions. Preoperative hemodynamic data, including mean pulmonary artery pressure, aortic valve area, aortic valve gradient, and ejection fraction (EF) were obtained from cardiac catheterization and echocardiography reports. Diagnoses of aortic stenosis (AS) or aortic insufficiency (AI) were determined by echocardiographic and intraoperative findings.
Patients who underwent operation within 24 hours of referral were classified as emergent. Patients undergoing AVR-CABG within the same hospitalization as the initial referral were considered urgent. All other operations were classified as elective. The selection of aortic valve prosthesis type was based on surgeon and patient preference. All patients who received a mechanical valve were placed on permanent anticoagulation. The standard of care at our institution for patients receiving a bioprosthetic valve is four to six weeks of anticoagulation postoperatively. Operative mortality was defined as death prior to discharge or any death within 30 days, even if the patient was discharged.
Statistical Analyses
Patients were divided into subgroups based on the number of bypass grafts that they received at the time of operation. To obtain patient subgroups of comparable size for analysis, patients who received three or four bypass grafts were grouped into one combined group (multiple bypass grafts group). For further analysis, patients were separated into groups according to the extent of CAD. Statistical analyses were performed with SPSS 13.0 software (SPSS Inc, Chicago, IL). The Pearson, 
2, Fisher, and analysis of variance tests were used to compare frequencies and means for preoperative and postoperative data among the patient groups depending on the comparison. In some instances, we analyzed two patient subgroups as discrete pairs to determine if there were any significant differences between individual groups. The Kaplan-Meier method was used to calculate both actuarial survival and freedom from repeat revascularization. Kaplan-Meier analysis of late survival was performed excluding those patients who were considered operative mortalities. Stepwise Cox proportional hazards model was used to determine the significant predictors of mortality. For our multivariate regression, all preoperative and hemodynamic variables were entered into the model, excluding those variables that were obvious confounding factors. For ease of analysis, some continuous variables were entered as discrete variables into the regression model. In all analyses, a p value less than 0.05 was considered statistically significant.
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Preoperative clinical characteristics are shown in Table 1. The three patient groups were well-matched over all relevant variables, although patients with one bypass graft had a significantly higher incidence of preoperative atrial fibrillation (Table 1). In addition, there were significantly fewer patients with aortic stenosis among patients who received two bypass grafts (Table 1). The incidence of hypertension was also lower in this group compared with the other two groups; however, this difference did not reach statistical significance. The number of patients with aortic insufficiency was similar in each group, and the mean operative age for the entire cohort was 73.6 ± 10.6 years.
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The operative mortality for the entire cohort was 9.4%. When stratified by the number of bypass grafts, operative mortality was similar in all three groups. Among patients who received one, two, and multiple bypass grafts, 8 (9.3%), 9 (11.1%), and 5 (7.6%) operative deaths occurred, respectively (p = 0.76, Table 4). When patients in the single bypass graft group were compared with the rest of the patient cohort, the operative mortality was similar: 9.3% vs 9.5% (p = 0.95). When stratified by the extent of CAD, operative mortality was higher among those patients with three-vessel disease: 9.0% (n = 6), 4.7% (n = 4), and 14.6% (n = 12), among those with one-, two-, and three-vessel CAD, respectively (p = 0.09).
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Incomplete Revascularization
Among all patients in our study cohort were 45 patients who were considered incompletely revascularized. For all patients, the reason for incomplete revascularization was poor distal target size or quality. Over the entire patient cohort, operative mortality was similar among patients who were incompletely revascularized (8.9%, n = 4) and those who were completely revascularized (9.6%, n = 18; p = 0.88). Late survival among those who survived the perioperative period was slightly improved for patients who were completely revascularized (one-year: 89.2%, two-year: 84.7%, five-year: 69.3%) compared with those who were incompletely revascularized (one-year: 83.3%, two-year: 77.4%, five-year: 61.0%), though this difference did not reach statistical significance (Fig 1,
p = 0.37).
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When stratified by the extent of CAD, there were no incompletely revascularized patients with one-vessel CAD, 21 patients with two-vessel CAD, and 24 patients with three-vessel CAD. Among those with two- and three-vessel CAD, there was no difference in operative mortality when compared by incomplete revascularization (both p > 0.72). There was also no difference in late survival within these two groups when completely and incompletely revascularized patients were compared (both p > 0.66).
Postoperative Outcomes
Significant postoperative morbidities, as well as mortality results, are summarized in Table 4. There was no significant difference in postoperative complications among the three patient groups. Also, the three patient groups did not differ in other postoperative morbidities, in addition to those shown in Table 4: frequency of myocardial infarction, atrial fibrillation, electrophysiologic pathology other than atrial fibrillation, bleeding requiring transfusion, bleeding related to anticoagulation, prolonged ventilator requirement (longer than seven days), pacemaker placement, and renal insufficiency.
Prior to AVR-CABG, 203 patients were either New York Heart Association (NYHA) class III or IV. More specifically, among patients who received one, two, and multiple bypass grafts, there were 65 (76%), 58 (72%), and 50 (76%) patients, respectively, who were class III/IV preoperatively. Figure 2 shows the postoperative improvements in NYHA class within these patient groups. There was a significant decrease in the number of class III/IV patients after AVR-CABG in all patient groups (Fig 2A–2C; all p < 0.001). Of particular note, there were higher percentages of patients (28%, n = 16) who remained NYHA class III/IV postoperatively in the two bypass grafts group compared with the other two patient groups (15% and 19% for one and multiple bypass grafts, respectively), though this difference was not significant (p = 0.25).
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Over a mean follow-up period of 2.2 ± 1.7 years (one patient lost to follow-up), there were six patients (2.6%) who had postoperative repeat revascularization. Of the patients who underwent repeat revascularization, two patients (0.9%) had redo CABG and four patients (1.8%) had percutaneous interventions including angioplasty and stenting. The two patients who underwent repeat revascularization in the one bypass group both had stent placement to a single vessel that was different from the originally grafted vessel during the AVR-CABG operation. In both cases, these were stenoses that were noted on preoperative catheterization but were not significant enough to warrant bypass grafting at the time of AVR-CABG. In the two bypass graft group, there were two patients who had repeat revascularization: one had stenting to a de novo lesion in a previously grafted LCX along with a new right coronary artery stent, and the other had a redo two-vessel CABG using two saphenous vein grafts to the same target vessels after the original IMA and saphenous vein grafts occluded. There was one patient who received three grafts at the initial operation who subsequently underwent a redo AVR-CABG with replacement of the original bypass grafts to the same distal targets and replacement of the bioprosthetic valve with a mechanical valve. Finally, one patient who originally received four bypass grafts was treated with a single-vessel stent to a previously bypassed LAD 62 months after initial AVR-CABG. Freedom from repeat revascularization for the entire patient cohort at one, two, and five years was 98.8%, 96.8%, and 96.8%, respectively. When separated by the number of bypass grafts, freedom from repeat revascularization at five years was similar among the three patient groups (p = 0.93, Fig 3). Finally, among patients with 1-, 2-, and 3-territory disease, the freedom from repeat revascularization at five years was 95.5%, 98.3%, and 96.5%, respectively (p = 0.99).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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The three patient subgroups in this study were well-matched in terms of preoperative clinical profile, preoperative hemodynamics, and operative data, although, as expected, patients who received more bypass grafts had a greater extent of CAD (Table 1). Patients in the single bypass graft group tended to have higher aortic valve gradients and aortic valve areas when compared with patients in the multiple bypass group. Excluding the presence of incomplete revascularization, this suggests that most patients in the single bypass graft group underwent AVR-CABG primarily for their valvular disease, while for most patients in the multiple bypass graft group this was not the case and the primary indication for surgery was less clear. Also, operations requiring more bypass grafts required longer cross-clamp and cardiopulmonary bypass times (Table 3). Overall, the similarity among the patient groups in this study allowed for an analysis that minimized the influence of potentially confounding factors.
There was no significant difference in postoperative morbidity among patients receiving increasing numbers of bypass grafts (Table 4). Despite the fact that patients who received multiple bypass grafts may have had more extensive and aggressive CAD, their postoperative morbidities were no different than the single bypass patients. All three groups demonstrated significant improvement in NYHA class, which is consistent with previous reports [4, 5, 9, 13, 14]. In addition, patients in our study enjoyed a low incidence of repeat revascularization at five years (3.2%), which was better than rates reported for isolated CABG (8.8%) [15].
Operative mortality for the entire cohort was 9.4%. No significant differences were observed when the cohort was analyzed by the number of bypass grafts, or completeness of revascularization. There was, however, significantly higher operative mortality among those patients with more extensive CAD. Operative mortality in our study were similar to those reported by previous studies, which ranged from 4.0% to 13.5% [4, 6, 7, 9, 12, 13, 16, 17]. More specifically, in these studies elderly AVR-CABG patients tended to have higher operative mortality [4, 13, 16]. Furthermore, the mortality of this study was slightly higher than those reported in the Society of Thoracic Surgeons National Database, which reports an operative mortality ranging from 5.5% to 7.5% for AVR-CABG procedures over the last 10 years [18]. It is difficult to determine, however, whether there are any competing variables, such as operative age, that could account for this difference.
As was observed with operative mortality, the number of bypass grafts did not influence late survival. Although extensive CAD negatively influenced early morality, this pattern was not maintained for late survival among patients in our study. Emergent operation, advanced age, worsened NYHA class, chronic obstructive pulmonary disease, and depressed EF were all significant predictors of mortality (Table 5). However, the number of diseased territories, the number of bypass grafts, incomplete revascularization, aortic stenosis, or aortic insufficiency did not predict late mortality in our Cox regression model. In addition, valve prosthesis type did not influence survival, consistent with two previous AVR-CABG studies [4, 13].
Although patients who received more bypass grafts tended to have more significant CAD, they also tended to have more complete revascularization and had outcomes that were similar to patients who had milder coronary disease and received fewer grafts. The results of our Cox regression suggest, however, that complete revascularization is not sufficient to account fully for this relative benefit among patients who received more grafts. Consistent with this, low-risk patients with extensive CAD enjoyed similar outcomes to higher risk patients with less extensive disease.
Several studies have documented five-year cumulative survivals higher (70% [6], 73% [9], 77% [12]) than the 63.3% from this study. However, these previous studies contain younger patients with higher preoperative ejection fractions. For example, the mean preoperative ejection fraction for AVR-CABG patients in the study by Czer and colleagues was 0.57 with a mean operative age of 67 [6]. Both of these factors were identified in this study as significant predictors of late mortality. When the results of this study were compared with studies with comparable mean operative ages, the five-year survivals were similar (63.3% vs 60% [4] and 63% [12]).
Several studies of isolated CABG [15, 19, 20] have reported results on the impact of multiple bypass grafting to a limited degree. Results from the Arterial Revascularization Therapies Study trial showed that there was no significant difference in event-free survival between those patients who received two- or three-vessel CABG [15]. In the study by Cosgrove and colleagues [19] there was no difference in overall mortality when patients were stratified by the number of bypass grafts. Finally, in the study by Lavee and colleagues [20], they found that a greater number of bypass grafts was associated with lower rates of perioperative mortality and postoperative angina. Further, performing complete revascularization with a greater number of bypass grafts did not increase operative risk in patients with advanced CAD [20].
While the above studies suggest that the number of bypass grafts does not affect outcomes in CABG, this issue is not as well-established for those patients undergoing a concomitant AVR procedure. One study by Kasimir and colleagues [10] demonstrated that the number of bypass grafts was not an independent predictor of death or worsened postoperative NYHA class among all patients undergoing combined valvular (not necessarily aortic valve) and coronary bypass surgery. Another study by Richardson and colleagues [5] showed that the number of bypass grafts was not associated with an increase in operative mortality or perioperative myocardial infarction. Although both studies indirectly address the impact of multiple bypass grafts, their analysis does not fully address the issue.
The purpose of our study was to investigate, deeply, the question of multiple bypass grafting in AVR-CABG. The fundamental balance is between the risk of performing more bypass grafting and the benefit of more complete revascularization. While in general our data revealed operative mortality and late survival to be independent of incomplete revascularization, more detailed analysis revealed a slightly higher operative mortality in the two bypass graft group when compared with the other two groups. This group is also the group in which there was a significantly higher percentage of incompletely revascularized patients. This link could suggest that early operative mortality is influenced negatively by incomplete revascularization. This mild difference is also seen with NYHA functional status: among patients in the two bypass graft group there was a higher percentage of patients who did not have a postoperative improvement to NYHA class I or II. Further, though the difference was not statistically significant, survival was lower for those patients who were incompletely revascularized when compared with those who were completely revascularized (Fig 1). Finally, patients in this two bypass graft group had decreased survival prior to the 2.5 year mark in our Kaplan-Meier analysis (Fig 4). All of the above suggest that although incomplete revascularization was not a predictor of late mortality in our multivariate regression, perhaps there is a significant difference that would be apparent with a larger sample size.
Paradoxically, the five-year survival for the patients in the two bypass graft group was the highest of the three patient groups. Therefore, while the early benefit of complete revascularization in the one and multiple bypass grafts groups can account for the early higher survival of these groups, there must be other factors that might explain the lower long-term survival. As was described earlier, patients in the single bypass graft group may be undergoing AVR-CABG to resolve more serious valvular disease than coronary disease. Thus, these patients enjoy a higher rate of complete revascularization; however, the increased severity of their valvular disease may eventually have a negative effect on late survival. On the other hand, the more severe coronary disease in those patients in the multiple bypass graft group may account for the decreased late survival. Thus, the two bypass group likely represents a set of patients with milder aortic valvular disease and CAD, and in addition includes a higher percentage of patients with multiple vessel disease who are incompletely revascularized. It is possible that the improved late survival of this patient group is due to the lesser long-term effects of the patients’ valvular and coronary disease. It is also possible that these patients were healthier preoperatively, as exemplified by the observed slightly lower incidence of hypertension in this group.
Our data clearly demonstrate that the number of bypass grafts performed during AVR-CABG is not a significant determinant of outcomes. Furthermore, as patients undergoing AVR-CABG are becoming older and presenting with poorer cardiac function, these results offer a more current picture of outcomes in AVR-CABG. Because the extent of coronary disease and incomplete revascularization negatively affect early and late mortality, and the number of bypass grafts does not confer additional risk, the benefits of complete revascularization outweigh the risks of a more involved procedure.
A retrospective study such as this cannot make absolute recommendations. However, based on our findings we recommend that as complete a revascularization be performed as is technically feasible and prudent under the clinical situation. The practice of doing the "most important graft" and leaving other vessels with significant stenoses ungrafted should be discouraged.
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Acknowledgments |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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References |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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