Early and late results of combined carotid endarterectomy and coronary artery bypass versus isolated coronary artery bypass
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《血管的通路杂志》
Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA
Presented at the ESCVS 54th International Congress of the European Society for Cardiovascular Surgery, Athens, Greece, May 19–22, 2005.
Abstract
Objective: Optimal management of patients with combined coronary and carotid artery disease remains controversial. This study analyzed the outcomes between simultaneous carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) vs. isolated CABG. Methods: We reviewed the early and late follow-up data of 412 patients who underwent either combined CEA/CABG vs. CABG alone between August 1999 and October 2003. All patients undergoing CEA had at least 80% stenosis of one carotid artery. Data were obtained for pre-, intra-, and early postoperative variables. Late follow-up data (range 1.1 to 69.5 months postoperative, mean 42.4 months, median 42.7 months) included myocardial infarctions (MI), stroke and death. Differences between the two groups were investigated. Univariate and multivariate analysis were carried out to identify predictors of death, MI, and stroke in the entire group. Results: There were 27 patients (6.6%) in the CEA/CABG group and 385 patients in the CABG alone group. There was one patient (3.7%) in the CEA/CABG group who had a perioperative stroke versus six (1.6%) in the CABG group (P=0.38). There were no documented postoperative myocardial infarctions (MI) by EKG and CK-MB criteria in both groups. There were no deaths in the CEA/CABG group versus three in the CABG group (P=1.00). Within the follow-up period, strokes developed in 2 (7.4%) CEA/CABG patients and in 7 (2.3%) CABG patients (P=0.16). Three CEA/CABG patients (11.1%) developed MI versus 19 (6.1%) patients in the CABG group (P=0.40). There were 4 (14.8%) deaths in the CEA/CABG group versus 51 (13.4%) in the CABG group (P=0.77). Freedom from death, stroke, and myocardial infarction was not statistically different between the groups at 60 months (all P>0.05). Conclusions: The addition of CEA to CABG did not increase short- and long-term morbidity and mortality compared to isolated CABG in our group of patients. Combined CEA/CABG can be performed safely in this high-risk group of patients. Prospective randomized study is needed to further substantiate these findings.
Key Words: Coronary artery bypass; Carotid endarterectomy; Combined coronary artery bypass and carotid endarterectomy; Carotid stenosis; Stroke
1. Introduction
The presence of significant carotid disease in patients undergoing coronary artery bypass surgery has been reported in the literature to be as high as 17% [1–4]. Considerable debate exists regarding the optimal treatment of such concomitant coronary and carotid artery disease.
One issue surrounding the controversy is the timing of surgery and the rates of stroke, myocardial infarction, and death associated with staged versus combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). Reports in the literature suggest that the staged approach, CEA followed by CABG, leads to a higher myocardial infarction rate [5–7]. On the other hand, studies involving CABG followed by CEA (reversed staged approach) have shown a higher stroke rate but a lower myocardial infarction rate [6,7]. In order to decrease the rate of mortality and risk of myocardial infarction and stroke, performing a CEA and CABG simultaneously (CEA/CABG) has been proposed, provided that the combined operation can be performed safely.
Bernhard and colleagues first described this combined approach in 1972 [8]. Since then, various groups have reported acceptable results [1,5–7,9–21]. There is wide variability in results, which may be due to patient selection criteria, age, various comorbidities, and different diagnostic modalities used for identifying carotid artery stenosis [22]. Most studies involving simultaneous CEA/CABG have been retrospective analyses and descriptive in nature. Bilfinger and coauthors conducted a prospective nonrandomized trial comparing comorbidities and outcomes in combined CEA/CABG procedures to CABG alone [1]. In this study, patients undergoing CEA/CABG were in a significantly higher risk group compared to those without such disease. However, patients without carotid disease who suffered perioperative stroke, were even higher risk group. In their univariate and multivariate analysis carotid endarterectomy was not a significant risk factor for perioperative stroke or mortality.
If the outcomes between two such groups, CEA/CABG vs. CABG alone, were to be the same, even though patients having the combined procedure appear to be a higher risk group, then it may seem reasonable to perform a combined procedure when warranted. Therefore, the aim of our study is to review and compare the risk factors and to assess the early and late outcomes in patients undergoing CABG alone versus simultaneous CEA/CABG.
2. Materials and methods
2.1. Study design
We reviewed the records of 412 consecutive patients who underwent either simultaneous coronary artery bypass surgery and carotid endarterectomy (CEA/CABG, n=27) or coronary artery bypass surgery alone (CABG, n=385) between August 1999 and October 2003. The same surgeon performed all coronary artery bypass surgeries and was present during all carotid endarterectomies.
Information collected for the New York State (NYS) Cardiac Surgery Reporting System (CSRS) was used to obtain patients' preoperative profiles, operative details, and postoperative data. This is a prospectively collected registry of all patients undergoing cardiac surgery in New York State. Late follow-up ranged from 1.1 to 69.5 months after operation (mean 42.4 months, median 42.7 months), which consisted of phone calls to patients or their family members or review of charts maintained by the patient's cardiologist. End points evaluated were myocardial infarction (MI), stroke, and death. The cause of death was categorized as MI, stroke, or other. Follow-up ended on April 15, 2005. For patients about whom we were unable to obtain information by the above methods, mortality data were collected by checking the social security death index and the corresponding date of death. Cause of death was undetermined for this set of patients and categorized as ‘unknown’. This is because the social security death index does not provide information about the cause of death.
Preoperative carotid duplex ultrasound was performed in all patients undergoing CABG. The percentage of diameter reduction was measured relative to the outflow vessel, according to the guidelines set by the Subcommittee on Reporting Standards for Cerebrovascular Disease [23]. All patients with more than or equal to 80% stenosis, whether symptomatic or asymptomatic, underwent magnetic resonance imaging and angiography (MRI/MRA) or carotid angiography in preparation for the CEA/CABG procedure. Two of the 27 patients who underwent the combined procedure had preoperative computer tomography (CT) scan of the brain that showed no evidence of stroke.
2.2. Operative information
2.2.1. CABG only group
Surgical myocardial revascularization was performed using the standard technique. Median sternotomy was performed and the patient was placed on cardiopulmonary bypass. The aorta was cross clamped and the heart was arrested with a combination of antegrade and retrograde cold blood cardioplegia. The left internal mammary artery was used when feasible to revascularize the left anterior descending (LAD) artery and additional venous or arterial conduits for the other target vessels.
2.2.2. CEA/CABG group
Median sternotomy was first performed simultaneously with vein harvest. This was followed by CEA. A shunt was used if the stump pressure was less than or equal to 50 mmHg. Patch carotid angioplasty was used in all patients. At the completion of the CEA, the neck wound was left open. CABG was performed as described above. All wounds were closed simultaneously after reversal of heparin. Neck drains were routinely used.
2.3. Statistical analysis
Data obtained from the patients' records were entered in a custom-designed database created in Microsoft Excel 2000, Version 9.0.2720. These data were then imported into SPSS version 13.0 (SPSS, Inc., Chicago, IL), which was used for all statistical computations. For all statistical tests P-values less than 0.05 were considered significant. All means are reported as mean±standard error mean (S.E.M.). Univariate comparison of continuous variables was performed using Student's t-test. Associations between categorical variables were tested by using Pearson's chi-square test. In cases where the calculated expected frequencies were less than 5, the Fisher's exact test was used. Kaplan–Meier curves were used to estimate the time-related probabilities of survival (freedom from late death) and freedom from late stroke and MI. The log rank test was used to compare the results between the CABG and CEA/CABG groups. Multivariate analyses using Cox regression were performed to identify the independent predictors of perioperative and late death, operative and late neurologic morbidity, and late MI. Predictors identified by univariate analysis with P values less than or equal to 0.1 were entered into the Cox regression and eliminated in a backwards stepwise manner. Likelihood ratio testing was used to test for significant differences between successive steps while constructing the model.
3. Results
3.1. Baseline demographics
Demographic and preoperative data are summarized in Table 1. Of the 27 patients who underwent simultaneous CEA/CABG, 20 (74.1%) were men and 7 (25.9%) were women. Their age ranged from 58 to 84 years with a mean of 70.3±1.5 years. A history of hypertension was present in 26 patients (96.3%); diabetes mellitus was present in 13 patients (48.1%). Twelve patients (44.4%) had a history of smoking at the time of the operation. Five patients (18.5%) had a history of a prior stroke(s). The ejection fraction was 54.0±2.6% (range, 25–82%), and 10 (29.6%) had left main disease.
Of the 385 patients who underwent CABG alone, 235 (61.0%) were men and 150 (39.0%) were women. Their age ranged from 35 to 96 years with a mean of 66.7±0.6 years. A history of hypertension was present in 329 patients (85.5%); diabetes mellitus was present in 162 patients (42.1%). One hundred and seventeen patients (30.4%) had a history of smoking at the time of the operation. Forty-three patients (11.2%) had a history of a prior stroke(s). The mean ejection fraction was 51.4±0.7% (range, 15–87%), and 86 patients (22.5%) had left main disease.
The combined group was significantly older than the control group (P=0.03). In addition, aorto/iliac disease and femoral/popliteal disease were more prevalent in the CEA/CABG group versus the CABG alone group (P=0.04 and P=0.048, respectively). History of a prior open-heart surgery was also more common in the combined group than the control group (P<0.01). The other baseline characteristics, such as gender, hypertension, diabetes, and smoking, were not statistically different between the two groups.
All CEA/CABG patients had more than or equal to 80% stenosis of at least one carotid artery. In the contralateral carotid artery, 13 (48.1%) had <50% stenosis, 10 (37%) had 50–79% stenosis, 2 (7.4%) had more than or equal to 80% stenosis, and 2 (7.4%) had complete occlusion. In the CABG group, 337 (87.5%) patients had no or <50% stenosis, 44 (11.4%) patients had 50–79% stenosis, and 4 (1%) had occlusion of one of the carotid arteries. Of these patients, 12 had bilateral stenoses of 50–79%.
3.2. Operative details
Distal anastomosis of the LAD was performed in 23 patients (85.2%) of the CEA/CABG group and 366 patients (95.1%) of the CABG group (P=0.06). The mean cardiopulmonary bypass time was 134.6±7.45 min (range, 72–238 min) in the CEA/CABG group versus 119.6±1.80 min (range, 13–269 min) in the CABG group (P=0.06). The mean aortic cross clamp time was 87.6±5.93 min (range, 34–177 min) in the CEA/CABG group and 76.8±1.17 min (range, 15–167 min) in the CABG group (P=0.03). The rest of the operative data were not statistically different between the CEA/CABG and CABG alone groups.
3.3. Early results
Thirty-day postoperative complications are summarized in Table 2. The operative mortality was 0% for CEA/CABG versus 0.8% (3 deaths) for CABG only (P=1.00). The causes of death were respiratory failure in two patients one of whom also had a stroke, and ischemic bowel in the other patient.
Cardiac complications that were evaluated included atrial fibrillation/atrial flutter (CEA/CABG n=5, 18.5%; CABG n=53, 13.8%; P=0.78), cardiac tamponade (CEA/CABG n=0; CABG n=2, 0.5%; P=1.00), and cardiac arrest (CEA/CABG n=0; CABG n=2, 0.5%; P=1.00). None of the patients in either group were documented to have a postoperative MI. The criteria used for the definition of MI were new Q-waves on EKG and/or enzyme elevation of CK-MB five times or more of the upper limit of normal. Perioperative strokes occurred in 1 CEA/CABG patient (3.7%) versus 6 CABG patients (1.6%) (P=0.38). The one stroke in the CEA/CABG group was identified upon the patient awakening from anesthesia and was contralateral to the operated carotid artery. Indeed, the stroke was ipsilateral to an occluded carotid artery. Out of the 6 strokes in the CEA/CABG group, five (1.3%) were identified upon awakening from anesthesia, and one developed during the postoperative hospitalization period. None of these 7 patients had aortic disease, or neurologic deficit preoperatively. Additionally, none of the 6 patients in the CABG/CEA group had more than 50% carotid artery stenosis. Transient ischemic attacks (TIA) developed in none of the CEA/CABG patients but in 1 (0.3%) CABG patient (P=1.00).
Respiratory failure occurred in 1 (3.7%) CEA/CABG patient and in 20 (5.2%) CABG patients (P=1.00). Acute renal insufficiency developed in no CEA/CABG patients but in 4 (1.0%) CABG patients (P=1.00). One (3.7%) CEA/CABG patient had bleeding requiring re-operation, whereas 5 (1.3%) instances occurred in the CABG group (P=0.34).
3.4. Late results
Late results are summarized in Table 3. Out of the 412 survivors from either operation, follow-up data on MI and stroke were obtained from 338 patients (82.0%). There were 27 patients in the CEA/CABG (100%) group and 311 patients in the CABG (81.4%) group. There was 100% follow-up on mortality rate and some were obtained through the social security death index; which however, does not provide any information regarding the cause of death. The follow-up time ranged from 1.1 to 69.5 months (mean 42.4 months, median 42.7 months).
During the follow-up period, three CEA/CABG patients (11.1%) experienced subsequent MI versus 19 (6.1%) patients in the CABG group (P=0.40). Strokes developed in 2 (7.4%) CEA/CABG patients and in 7 (2.3%) CABG patients (P=0.16). Of the strokes that occurred in the CEA/CABG group, one was contralateral and the other was ipsilateral to the site of endarterectomy. TIAs did not develop in the CEA/CABG group compared to 12 patients (3.9%) in the CABG group (P=0.61).
The overall late mortality was 13.3% (55 patients). There were 4 (14.8%) deaths in the CEA/CABG group versus 51 (13.4%) in the CABG group (P=0.77). Of those deaths, none were attributed to stroke in either the CEA/CABG group or the CABG group. There were no deaths due to MI in the CEA/CABG group, but there were 6 (1.6%) in the CABG group (P=1.00). Three patients (11.1%) in the CEA/CABG group and 27 (7.1%) patients in the CABG group died from a cause other than MI or stroke (P=0.44). One CEA/CABG (3.7%) patient and 18 (4.7%) CABG patients died of an unknown cause (P=1.00).
Figs. 1–3 show Kaplan–Meier analyses of late death, MI and stroke for the two groups with table inserts that show the number of patients at risk at each time period. The 5-year overall survival between the two groups was not significantly different (Fig. 1) by the log rank test (P=0.62). In addition, the freedom from late stroke (Fig. 2) and MI (Fig. 3) was not significantly different between the CEA/CABG vs. CABG alone groups (P=0.10 and P=0.19, respectively).
Univariate analysis identified several predictors for late death, MI, and stroke. The significant predictors for death are shown in Table 4, which include age, prior congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), renal failure (Cr 2.5 mg/dl), perioperative stroke, atrial fibrillation/flutter, and ejection fraction (all P<0.05). The only significant univariate predictor of late MI was male sex (P=0.02). Multivariate predictors of late mortality were age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05–1.14), prior CHF (OR 2.63, 95% CI 1.37–5.26), and re-intubation (OR 4.76, 95% CI 1.92–11.11). Male sex was the only multivariate predictor of late MI (OR 4.00, 95% CI 1.16–14.29). There were no significant univariate or multivariate predictors for late stroke.
4. Discussion
The reported incidence of carotid artery stenosis in patients undergoing carotid bypass grafting varies widely depending primarily on the grade of stenosis considered significant and the modality used to screen the carotids [1–4]. Some authors perform routine screening of all patients undergoing CABG [1], while others advocate utilization of specific risk factors to direct screening [2]. Although performing CEA in this select group of CABG patients with significant carotid disease may reduce risk of perioperative complications, the benefits of CEA should not be measured only within this limited context. Rather, long-term stroke prevention is the most important objective of carotid endarterectomy in most patients, and it is no less so among those who require other major cardiovascular procedures. Because such severe carotid disease warrants surgical intervention on these grounds alone, it seems appropriate to correct it in conjunction with CABG to achieve any additional protection from perioperative stroke that this approach may provide.
However, optimal management of patients with severe coronary and high-grade carotid stenosis is not well supported by level one evidence. Although the majority of the studies support combined CEA/CABG [1,5–21], most of these studies are retrospective analyses and descriptive in nature. There is only one study with an element of prospective randomization [5]. In the current paper, the data for patients undergoing CABG versus combined CEA/CABG by a single surgeon were analyzed to determine early and late outcomes.
Naylor and coauthors conducted a systematic review of the literature published between 1972 and 2002 comparing staged and synchronous CEA and CABG [7]. The combined approach was performed in 7753 cases with operative mortality rate of 4.6%, and stroke rate of 4.6%, and MI rate of 3.6%. The overall combined mortality, stroke, and MI rate was 11.5%. Among the 917 cases that underwent staged CEA followed by CABG, the operative mortality rate was 3.9%, the stroke rate was 2.7%, and the MI rate was 6.5%. The combined mortality, stroke and MI rate was 10.2%. The corresponding data for 302 cases of reversed staged CABG/CEA was 2%, 6.3%, 0.9% and 5%, respectively. Overall, there was no significant difference in outcomes for staged and synchronous procedures.
These data must be weighed against a population-based outcome report of Medicare patients from 10 states in the USA between June 1, 1995 and May 31, 1996, which showed a higher morbidity and mortality [24]. Of the 10,561 CEA procedures reviewed, 226 procedures were performed in combination with CABG in the same operative event. The mortality rate was 6.6% and overall stroke rate was 12%. Combined stroke and mortality rate was 17.7%. Of note is that most of the strokes were not limited to the ipsilateral carotid territory and, therefore, may have been unrelated to the CEA.
A recent case-controlled study from the New York State Cardiac Surgery Reporting Data compared patients undergoing CEA/CABG with risk-matched cohort of patients after isolated CABG [25]. The 744 combined CEA/CABG patients had higher postoperative complications than the 35,539 isolated CABG patients, but they also had a higher overall risk profile. After risk-factor matching, no differences in stroke (5.1 vs. 5%), death (4.4 vs. 3.9%), or combined stroke and death (8.1 vs. 8.5%) were observed. The authors concluded that the observed differences in major morbidity of patients undergoing CEA/CABG compared to CABG in cohort studies are due to inherent risk factors of the first group of patients, and not secondary to adding CEA to the coronary surgery.
The results presented in this study are in agreement with the reports of the combined approach. Our patients in the combined group were older and had a higher incidence of aorto-iliac and peripheral vascular disease (Table 1), as well as longer cross clamp time in the operating room. The incidence of perioperative MI, stroke, and operative mortality was 0%, 3.7%, and 0% in CEA/CAB group versus 0%, 1.6%, and 0.8% in patients undergoing CABG, respectively. These were not statistically different (Table 2). The long-term survival was 85.2% in the CEA/CABG group versus 86.6% in the CABG group. Furthermore, 11.1%, and 7.4% of patients undergoing CEA/CABG experienced MI and stroke versus 6.1 and 2.3% patients in the CABG group, respectively. These results did not reach a statistical difference (Table 3). The above data imply that despite the fact that patients requiring CEA/CABG have higher preoperative risk factors, concomitant CEA did not confer additional morbidity or mortality.
Univariate and multivariate analyses were performed to investigate independent risk factors for late MI, stroke, and death in both groups. The only significant parameters were older age, prior history of CHF, and postoperative re-intubation, which were found to be independent risk factors of late mortality in multivariate analysis. Male sex was the only independent risk factor for developing a myocardial infarction in the early and late postoperative period.
Limitations of this study are the number of patients undergoing CEA/CABG. Higher statistical power could have helped in identifying differences in outcome and in this subset of patients. Lack of randomization of patients and retrospective collection of long-term data are also limiting factors.
In summary, the early and late outcomes for our patients undergoing CEA/CABG versus CABG are comparable. Although patients requiring CEA/CABG have higher preoperative risk factors, the combined approach was performed with low rates of myocardial infarction, stroke, and mortality in early postoperative period. These benefits are maintained in the long-term follow-up. A large randomized controlled trial is necessary to substantiate the results in this study.
Acknowledgements
The authors wish to thank Fred Wasserman for his exceptional assistance with the study.
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Presented at the ESCVS 54th International Congress of the European Society for Cardiovascular Surgery, Athens, Greece, May 19–22, 2005.
Abstract
Objective: Optimal management of patients with combined coronary and carotid artery disease remains controversial. This study analyzed the outcomes between simultaneous carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) vs. isolated CABG. Methods: We reviewed the early and late follow-up data of 412 patients who underwent either combined CEA/CABG vs. CABG alone between August 1999 and October 2003. All patients undergoing CEA had at least 80% stenosis of one carotid artery. Data were obtained for pre-, intra-, and early postoperative variables. Late follow-up data (range 1.1 to 69.5 months postoperative, mean 42.4 months, median 42.7 months) included myocardial infarctions (MI), stroke and death. Differences between the two groups were investigated. Univariate and multivariate analysis were carried out to identify predictors of death, MI, and stroke in the entire group. Results: There were 27 patients (6.6%) in the CEA/CABG group and 385 patients in the CABG alone group. There was one patient (3.7%) in the CEA/CABG group who had a perioperative stroke versus six (1.6%) in the CABG group (P=0.38). There were no documented postoperative myocardial infarctions (MI) by EKG and CK-MB criteria in both groups. There were no deaths in the CEA/CABG group versus three in the CABG group (P=1.00). Within the follow-up period, strokes developed in 2 (7.4%) CEA/CABG patients and in 7 (2.3%) CABG patients (P=0.16). Three CEA/CABG patients (11.1%) developed MI versus 19 (6.1%) patients in the CABG group (P=0.40). There were 4 (14.8%) deaths in the CEA/CABG group versus 51 (13.4%) in the CABG group (P=0.77). Freedom from death, stroke, and myocardial infarction was not statistically different between the groups at 60 months (all P>0.05). Conclusions: The addition of CEA to CABG did not increase short- and long-term morbidity and mortality compared to isolated CABG in our group of patients. Combined CEA/CABG can be performed safely in this high-risk group of patients. Prospective randomized study is needed to further substantiate these findings.
Key Words: Coronary artery bypass; Carotid endarterectomy; Combined coronary artery bypass and carotid endarterectomy; Carotid stenosis; Stroke
1. Introduction
The presence of significant carotid disease in patients undergoing coronary artery bypass surgery has been reported in the literature to be as high as 17% [1–4]. Considerable debate exists regarding the optimal treatment of such concomitant coronary and carotid artery disease.
One issue surrounding the controversy is the timing of surgery and the rates of stroke, myocardial infarction, and death associated with staged versus combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). Reports in the literature suggest that the staged approach, CEA followed by CABG, leads to a higher myocardial infarction rate [5–7]. On the other hand, studies involving CABG followed by CEA (reversed staged approach) have shown a higher stroke rate but a lower myocardial infarction rate [6,7]. In order to decrease the rate of mortality and risk of myocardial infarction and stroke, performing a CEA and CABG simultaneously (CEA/CABG) has been proposed, provided that the combined operation can be performed safely.
Bernhard and colleagues first described this combined approach in 1972 [8]. Since then, various groups have reported acceptable results [1,5–7,9–21]. There is wide variability in results, which may be due to patient selection criteria, age, various comorbidities, and different diagnostic modalities used for identifying carotid artery stenosis [22]. Most studies involving simultaneous CEA/CABG have been retrospective analyses and descriptive in nature. Bilfinger and coauthors conducted a prospective nonrandomized trial comparing comorbidities and outcomes in combined CEA/CABG procedures to CABG alone [1]. In this study, patients undergoing CEA/CABG were in a significantly higher risk group compared to those without such disease. However, patients without carotid disease who suffered perioperative stroke, were even higher risk group. In their univariate and multivariate analysis carotid endarterectomy was not a significant risk factor for perioperative stroke or mortality.
If the outcomes between two such groups, CEA/CABG vs. CABG alone, were to be the same, even though patients having the combined procedure appear to be a higher risk group, then it may seem reasonable to perform a combined procedure when warranted. Therefore, the aim of our study is to review and compare the risk factors and to assess the early and late outcomes in patients undergoing CABG alone versus simultaneous CEA/CABG.
2. Materials and methods
2.1. Study design
We reviewed the records of 412 consecutive patients who underwent either simultaneous coronary artery bypass surgery and carotid endarterectomy (CEA/CABG, n=27) or coronary artery bypass surgery alone (CABG, n=385) between August 1999 and October 2003. The same surgeon performed all coronary artery bypass surgeries and was present during all carotid endarterectomies.
Information collected for the New York State (NYS) Cardiac Surgery Reporting System (CSRS) was used to obtain patients' preoperative profiles, operative details, and postoperative data. This is a prospectively collected registry of all patients undergoing cardiac surgery in New York State. Late follow-up ranged from 1.1 to 69.5 months after operation (mean 42.4 months, median 42.7 months), which consisted of phone calls to patients or their family members or review of charts maintained by the patient's cardiologist. End points evaluated were myocardial infarction (MI), stroke, and death. The cause of death was categorized as MI, stroke, or other. Follow-up ended on April 15, 2005. For patients about whom we were unable to obtain information by the above methods, mortality data were collected by checking the social security death index and the corresponding date of death. Cause of death was undetermined for this set of patients and categorized as ‘unknown’. This is because the social security death index does not provide information about the cause of death.
Preoperative carotid duplex ultrasound was performed in all patients undergoing CABG. The percentage of diameter reduction was measured relative to the outflow vessel, according to the guidelines set by the Subcommittee on Reporting Standards for Cerebrovascular Disease [23]. All patients with more than or equal to 80% stenosis, whether symptomatic or asymptomatic, underwent magnetic resonance imaging and angiography (MRI/MRA) or carotid angiography in preparation for the CEA/CABG procedure. Two of the 27 patients who underwent the combined procedure had preoperative computer tomography (CT) scan of the brain that showed no evidence of stroke.
2.2. Operative information
2.2.1. CABG only group
Surgical myocardial revascularization was performed using the standard technique. Median sternotomy was performed and the patient was placed on cardiopulmonary bypass. The aorta was cross clamped and the heart was arrested with a combination of antegrade and retrograde cold blood cardioplegia. The left internal mammary artery was used when feasible to revascularize the left anterior descending (LAD) artery and additional venous or arterial conduits for the other target vessels.
2.2.2. CEA/CABG group
Median sternotomy was first performed simultaneously with vein harvest. This was followed by CEA. A shunt was used if the stump pressure was less than or equal to 50 mmHg. Patch carotid angioplasty was used in all patients. At the completion of the CEA, the neck wound was left open. CABG was performed as described above. All wounds were closed simultaneously after reversal of heparin. Neck drains were routinely used.
2.3. Statistical analysis
Data obtained from the patients' records were entered in a custom-designed database created in Microsoft Excel 2000, Version 9.0.2720. These data were then imported into SPSS version 13.0 (SPSS, Inc., Chicago, IL), which was used for all statistical computations. For all statistical tests P-values less than 0.05 were considered significant. All means are reported as mean±standard error mean (S.E.M.). Univariate comparison of continuous variables was performed using Student's t-test. Associations between categorical variables were tested by using Pearson's chi-square test. In cases where the calculated expected frequencies were less than 5, the Fisher's exact test was used. Kaplan–Meier curves were used to estimate the time-related probabilities of survival (freedom from late death) and freedom from late stroke and MI. The log rank test was used to compare the results between the CABG and CEA/CABG groups. Multivariate analyses using Cox regression were performed to identify the independent predictors of perioperative and late death, operative and late neurologic morbidity, and late MI. Predictors identified by univariate analysis with P values less than or equal to 0.1 were entered into the Cox regression and eliminated in a backwards stepwise manner. Likelihood ratio testing was used to test for significant differences between successive steps while constructing the model.
3. Results
3.1. Baseline demographics
Demographic and preoperative data are summarized in Table 1. Of the 27 patients who underwent simultaneous CEA/CABG, 20 (74.1%) were men and 7 (25.9%) were women. Their age ranged from 58 to 84 years with a mean of 70.3±1.5 years. A history of hypertension was present in 26 patients (96.3%); diabetes mellitus was present in 13 patients (48.1%). Twelve patients (44.4%) had a history of smoking at the time of the operation. Five patients (18.5%) had a history of a prior stroke(s). The ejection fraction was 54.0±2.6% (range, 25–82%), and 10 (29.6%) had left main disease.
Of the 385 patients who underwent CABG alone, 235 (61.0%) were men and 150 (39.0%) were women. Their age ranged from 35 to 96 years with a mean of 66.7±0.6 years. A history of hypertension was present in 329 patients (85.5%); diabetes mellitus was present in 162 patients (42.1%). One hundred and seventeen patients (30.4%) had a history of smoking at the time of the operation. Forty-three patients (11.2%) had a history of a prior stroke(s). The mean ejection fraction was 51.4±0.7% (range, 15–87%), and 86 patients (22.5%) had left main disease.
The combined group was significantly older than the control group (P=0.03). In addition, aorto/iliac disease and femoral/popliteal disease were more prevalent in the CEA/CABG group versus the CABG alone group (P=0.04 and P=0.048, respectively). History of a prior open-heart surgery was also more common in the combined group than the control group (P<0.01). The other baseline characteristics, such as gender, hypertension, diabetes, and smoking, were not statistically different between the two groups.
All CEA/CABG patients had more than or equal to 80% stenosis of at least one carotid artery. In the contralateral carotid artery, 13 (48.1%) had <50% stenosis, 10 (37%) had 50–79% stenosis, 2 (7.4%) had more than or equal to 80% stenosis, and 2 (7.4%) had complete occlusion. In the CABG group, 337 (87.5%) patients had no or <50% stenosis, 44 (11.4%) patients had 50–79% stenosis, and 4 (1%) had occlusion of one of the carotid arteries. Of these patients, 12 had bilateral stenoses of 50–79%.
3.2. Operative details
Distal anastomosis of the LAD was performed in 23 patients (85.2%) of the CEA/CABG group and 366 patients (95.1%) of the CABG group (P=0.06). The mean cardiopulmonary bypass time was 134.6±7.45 min (range, 72–238 min) in the CEA/CABG group versus 119.6±1.80 min (range, 13–269 min) in the CABG group (P=0.06). The mean aortic cross clamp time was 87.6±5.93 min (range, 34–177 min) in the CEA/CABG group and 76.8±1.17 min (range, 15–167 min) in the CABG group (P=0.03). The rest of the operative data were not statistically different between the CEA/CABG and CABG alone groups.
3.3. Early results
Thirty-day postoperative complications are summarized in Table 2. The operative mortality was 0% for CEA/CABG versus 0.8% (3 deaths) for CABG only (P=1.00). The causes of death were respiratory failure in two patients one of whom also had a stroke, and ischemic bowel in the other patient.
Cardiac complications that were evaluated included atrial fibrillation/atrial flutter (CEA/CABG n=5, 18.5%; CABG n=53, 13.8%; P=0.78), cardiac tamponade (CEA/CABG n=0; CABG n=2, 0.5%; P=1.00), and cardiac arrest (CEA/CABG n=0; CABG n=2, 0.5%; P=1.00). None of the patients in either group were documented to have a postoperative MI. The criteria used for the definition of MI were new Q-waves on EKG and/or enzyme elevation of CK-MB five times or more of the upper limit of normal. Perioperative strokes occurred in 1 CEA/CABG patient (3.7%) versus 6 CABG patients (1.6%) (P=0.38). The one stroke in the CEA/CABG group was identified upon the patient awakening from anesthesia and was contralateral to the operated carotid artery. Indeed, the stroke was ipsilateral to an occluded carotid artery. Out of the 6 strokes in the CEA/CABG group, five (1.3%) were identified upon awakening from anesthesia, and one developed during the postoperative hospitalization period. None of these 7 patients had aortic disease, or neurologic deficit preoperatively. Additionally, none of the 6 patients in the CABG/CEA group had more than 50% carotid artery stenosis. Transient ischemic attacks (TIA) developed in none of the CEA/CABG patients but in 1 (0.3%) CABG patient (P=1.00).
Respiratory failure occurred in 1 (3.7%) CEA/CABG patient and in 20 (5.2%) CABG patients (P=1.00). Acute renal insufficiency developed in no CEA/CABG patients but in 4 (1.0%) CABG patients (P=1.00). One (3.7%) CEA/CABG patient had bleeding requiring re-operation, whereas 5 (1.3%) instances occurred in the CABG group (P=0.34).
3.4. Late results
Late results are summarized in Table 3. Out of the 412 survivors from either operation, follow-up data on MI and stroke were obtained from 338 patients (82.0%). There were 27 patients in the CEA/CABG (100%) group and 311 patients in the CABG (81.4%) group. There was 100% follow-up on mortality rate and some were obtained through the social security death index; which however, does not provide any information regarding the cause of death. The follow-up time ranged from 1.1 to 69.5 months (mean 42.4 months, median 42.7 months).
During the follow-up period, three CEA/CABG patients (11.1%) experienced subsequent MI versus 19 (6.1%) patients in the CABG group (P=0.40). Strokes developed in 2 (7.4%) CEA/CABG patients and in 7 (2.3%) CABG patients (P=0.16). Of the strokes that occurred in the CEA/CABG group, one was contralateral and the other was ipsilateral to the site of endarterectomy. TIAs did not develop in the CEA/CABG group compared to 12 patients (3.9%) in the CABG group (P=0.61).
The overall late mortality was 13.3% (55 patients). There were 4 (14.8%) deaths in the CEA/CABG group versus 51 (13.4%) in the CABG group (P=0.77). Of those deaths, none were attributed to stroke in either the CEA/CABG group or the CABG group. There were no deaths due to MI in the CEA/CABG group, but there were 6 (1.6%) in the CABG group (P=1.00). Three patients (11.1%) in the CEA/CABG group and 27 (7.1%) patients in the CABG group died from a cause other than MI or stroke (P=0.44). One CEA/CABG (3.7%) patient and 18 (4.7%) CABG patients died of an unknown cause (P=1.00).
Figs. 1–3 show Kaplan–Meier analyses of late death, MI and stroke for the two groups with table inserts that show the number of patients at risk at each time period. The 5-year overall survival between the two groups was not significantly different (Fig. 1) by the log rank test (P=0.62). In addition, the freedom from late stroke (Fig. 2) and MI (Fig. 3) was not significantly different between the CEA/CABG vs. CABG alone groups (P=0.10 and P=0.19, respectively).
Univariate analysis identified several predictors for late death, MI, and stroke. The significant predictors for death are shown in Table 4, which include age, prior congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), renal failure (Cr 2.5 mg/dl), perioperative stroke, atrial fibrillation/flutter, and ejection fraction (all P<0.05). The only significant univariate predictor of late MI was male sex (P=0.02). Multivariate predictors of late mortality were age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05–1.14), prior CHF (OR 2.63, 95% CI 1.37–5.26), and re-intubation (OR 4.76, 95% CI 1.92–11.11). Male sex was the only multivariate predictor of late MI (OR 4.00, 95% CI 1.16–14.29). There were no significant univariate or multivariate predictors for late stroke.
4. Discussion
The reported incidence of carotid artery stenosis in patients undergoing carotid bypass grafting varies widely depending primarily on the grade of stenosis considered significant and the modality used to screen the carotids [1–4]. Some authors perform routine screening of all patients undergoing CABG [1], while others advocate utilization of specific risk factors to direct screening [2]. Although performing CEA in this select group of CABG patients with significant carotid disease may reduce risk of perioperative complications, the benefits of CEA should not be measured only within this limited context. Rather, long-term stroke prevention is the most important objective of carotid endarterectomy in most patients, and it is no less so among those who require other major cardiovascular procedures. Because such severe carotid disease warrants surgical intervention on these grounds alone, it seems appropriate to correct it in conjunction with CABG to achieve any additional protection from perioperative stroke that this approach may provide.
However, optimal management of patients with severe coronary and high-grade carotid stenosis is not well supported by level one evidence. Although the majority of the studies support combined CEA/CABG [1,5–21], most of these studies are retrospective analyses and descriptive in nature. There is only one study with an element of prospective randomization [5]. In the current paper, the data for patients undergoing CABG versus combined CEA/CABG by a single surgeon were analyzed to determine early and late outcomes.
Naylor and coauthors conducted a systematic review of the literature published between 1972 and 2002 comparing staged and synchronous CEA and CABG [7]. The combined approach was performed in 7753 cases with operative mortality rate of 4.6%, and stroke rate of 4.6%, and MI rate of 3.6%. The overall combined mortality, stroke, and MI rate was 11.5%. Among the 917 cases that underwent staged CEA followed by CABG, the operative mortality rate was 3.9%, the stroke rate was 2.7%, and the MI rate was 6.5%. The combined mortality, stroke and MI rate was 10.2%. The corresponding data for 302 cases of reversed staged CABG/CEA was 2%, 6.3%, 0.9% and 5%, respectively. Overall, there was no significant difference in outcomes for staged and synchronous procedures.
These data must be weighed against a population-based outcome report of Medicare patients from 10 states in the USA between June 1, 1995 and May 31, 1996, which showed a higher morbidity and mortality [24]. Of the 10,561 CEA procedures reviewed, 226 procedures were performed in combination with CABG in the same operative event. The mortality rate was 6.6% and overall stroke rate was 12%. Combined stroke and mortality rate was 17.7%. Of note is that most of the strokes were not limited to the ipsilateral carotid territory and, therefore, may have been unrelated to the CEA.
A recent case-controlled study from the New York State Cardiac Surgery Reporting Data compared patients undergoing CEA/CABG with risk-matched cohort of patients after isolated CABG [25]. The 744 combined CEA/CABG patients had higher postoperative complications than the 35,539 isolated CABG patients, but they also had a higher overall risk profile. After risk-factor matching, no differences in stroke (5.1 vs. 5%), death (4.4 vs. 3.9%), or combined stroke and death (8.1 vs. 8.5%) were observed. The authors concluded that the observed differences in major morbidity of patients undergoing CEA/CABG compared to CABG in cohort studies are due to inherent risk factors of the first group of patients, and not secondary to adding CEA to the coronary surgery.
The results presented in this study are in agreement with the reports of the combined approach. Our patients in the combined group were older and had a higher incidence of aorto-iliac and peripheral vascular disease (Table 1), as well as longer cross clamp time in the operating room. The incidence of perioperative MI, stroke, and operative mortality was 0%, 3.7%, and 0% in CEA/CAB group versus 0%, 1.6%, and 0.8% in patients undergoing CABG, respectively. These were not statistically different (Table 2). The long-term survival was 85.2% in the CEA/CABG group versus 86.6% in the CABG group. Furthermore, 11.1%, and 7.4% of patients undergoing CEA/CABG experienced MI and stroke versus 6.1 and 2.3% patients in the CABG group, respectively. These results did not reach a statistical difference (Table 3). The above data imply that despite the fact that patients requiring CEA/CABG have higher preoperative risk factors, concomitant CEA did not confer additional morbidity or mortality.
Univariate and multivariate analyses were performed to investigate independent risk factors for late MI, stroke, and death in both groups. The only significant parameters were older age, prior history of CHF, and postoperative re-intubation, which were found to be independent risk factors of late mortality in multivariate analysis. Male sex was the only independent risk factor for developing a myocardial infarction in the early and late postoperative period.
Limitations of this study are the number of patients undergoing CEA/CABG. Higher statistical power could have helped in identifying differences in outcome and in this subset of patients. Lack of randomization of patients and retrospective collection of long-term data are also limiting factors.
In summary, the early and late outcomes for our patients undergoing CEA/CABG versus CABG are comparable. Although patients requiring CEA/CABG have higher preoperative risk factors, the combined approach was performed with low rates of myocardial infarction, stroke, and mortality in early postoperative period. These benefits are maintained in the long-term follow-up. A large randomized controlled trial is necessary to substantiate the results in this study.
Acknowledgements
The authors wish to thank Fred Wasserman for his exceptional assistance with the study.
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