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Ann Thorac Surg 2007;83:1679-1683
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Predictors of Early Postoperative Cerebral Infarction After Isolated Off-Pump Coronary Artery Bypass Grafting

Keiju Kotoh, MD, PhD*, Kazuaki Fukahara, MD, PhD, Toshio Doi, MD, PhD, Saori Nagura, MD, Takuro Misaki, MD, PhD

Department of Surgery, University of Toyama, Toyama, Japan

Accepted for publication December 29, 2006.

* Address correspondence to Dr Kotoh, Department of Surgery, University of Toyama, 2630 Sugitani Toyama, Japan, 930-0194 (Email: kotoh{at}med.u-toyama.ac.jp).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Risk factors associated with cerebral infarction within 7 days after off-pump coronary artery bypass grafting require further statistical elucidation.

Methods: From January 1997 to July 2006, off-pump coronary artery bypass grafting was performed in 576 patients at Toyama University Hospital. Factors including previous cerebral infarction, lesions in head and neck vessels, preoperative cerebral ischemic symptoms, intraaortic balloon pump use, number of coronary lesions, number of coronary bypasses, sites of coronary bypasses, number of proximal anastomoses in the ascending aorta, use of aortic no-touch procedure, partial aortic clamping, automatic proximal anastomosis devices, and a proximal seal system were compared retrospectively between patients with and without early cerebral infarction. Factors differing between groups were analyzed further by multivariate logistic regression.

Results: Ten patients (1.7%) had cerebral infarction within 7 days after surgery. The subjects were divided into two groups, those who had cerebral infarction after surgery (n = 10) and those who did not (n = 566). Factors showing significant intergroup differences were a previous history of cerebral infarction (p < 0.001), preoperative presence of cerebral ischemic symptoms (p < 0.001), vascular lesions in head and neck vessels (p < 0.001), use of partial aortic clamping (p = 0.002), and postoperative atrial fibrillation within 7 days after surgery (p = 0.011). Multiple logistic regression analysis indicated close relationships between previous history of cerebral infarction (odds ratio, 26.6; 95% confidence interval, 2.8 to 251.1; p = 0.004), preoperative presence of cerebral ischemic symptoms plus lesions in head and neck vessels (odds ratio, 22.8; 95% confidence interval 1.8 to 285.7; p = 0.015), and use of partial aortic clamping (odds ratio, 11.1; 95% confidence interval, 1.4 to 85.7; p = 0.021). Postoperative atrial fibrillation within 7 days after surgery (odds ratio, 3.4; 95% confidence interval, 0.7 to 16.5; p = 0.121) was suspected as a risk factor for postoperative cerebral infarction.

Conclusions: Multivariate analysis identified independent factors strongly associated with cerebral infarction after off-pump coronary artery bypass grafting, such as partial aortic clamping, presence of cerebral ischemic symptoms plus head and neck vascular lesions, and previous cerebral infarction.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Owing to various technical advances, performance of off-pump coronary artery bypass grafting (off-pump CABG) has increased. However, postoperative cerebral infarction remains a major problem in these cases, with an incidence ranging from 0.6% to 3.8% for off-pump CABG [1–3], as high as that reported for coronary artery bypass grafting (CABG) performed with cardiopulmonary bypass. In the present study we identified factors causing cerebral infarction in the early stage after off-pump CABG.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
From January 1997 to July 2006, isolated CABG was performed in 622 patients at Toyama University Hospital. Our institutional ethics committee waived the need for patients’ consent for this study, and approval was provided before publication of this manuscript and report of the information. Five hundred seventy-six patients were operated on using off-pump CABG, and 46 patients were operated on using CABG with cardiopulmonary bypass. Ten of these 46 patients had converted from off-pump CABG to CABG with cardiopulmonary bypass. Indications for off-pump CABG included patients with the possibility to expose epicardial target vessels 1 mm or larger. Contraindication to off-pump CABG included patients with coexistence of aortic or mitral regurgitation, small intramyocardial coronary targets, and unstable hemodynamic conditions by using off-pump approach. Coronary artery bypass grafting with cardiopulmonary bypass was performed for all cases with contraindications to off-pump CABG.

Five hundred seventy-six patients who were operated on using off-pump CABG were included in this study.

Preoperative Data
Preoperative patient profile data are summarized in Table 1. The mean age of the patients (446 male, 130 female) was 67.3 ± 10.0 years. Fifty-three patients (9.2%) had vascular lesions in the head and neck vessels. Vascular lesions were defined as a stenosis of more than 75% of the internal carotid artery, vertebral artery, and intracranial cerebral artery. Fifteen patients (2.6%) had preoperative cerebral ischemic symptoms such as transient motor disorder, vertigo, and syncope attack.


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  		Table 1 Patient Clinical Characteristics
 
Operative Technique
Off-pump CABG approaches were direct CABG through a left anterior thoracotomy and a median sternotomy. Indication for a left anterior thoracotomy included isolated proximal disease of the left anterior descending or first diagonal artery. In multivessel disease, a median sternotomy approach was favored.

Left anterior thoracotomy approach
The patients were intubated with a double-lumen endotracheal tube to permit selective ventilation. A left anterior thoracotomy in the fourth intercostal space was performed under general anesthesia. The details of our surgical technique for a left anterior thoracotomy have been reported by Watanabe and colleagues [4]. An Octopus 4.3 cardiac stabilizer (Medtronic, Minneapolis, MN) was used for fixing the coronary artery. Before the arterial conduits were divided, heparin sodium (1.5 mg/kg) was given intravenously. At the time of anastomosis of the anterior descending artery, flow was maintained by use of an external shunt tube. After the anastomosis, protamine sulfate (0.75 mg/kg) was given intravenously.

Median sternotomy approach
A median sternotomy was performed under general anesthesia. For the operative procedure the heart was displaced by applying traction to the pericardium with a supporting thread as reported by Baumgrtner and coworkers [5]. An Octopus IV cardiac stabilizer (Medtronic) was used for fixing the coronary artery. To expose the circumflex artery, right coronary artery, and posterior descending artery, a Starfish heart positioner (Medtronic) was used. Before the arterial conduits were divided, heparin sodium (1.5 mg/kg) was given intravenously. At the time of anastomosis of the anterior descending artery or right coronary artery, flow was maintained by use of an external shunt tube, whereas during anastomosis of the circumflex artery or posterior descending artery, coronary flow was transiently occluded by simple clamping. After the anastomosis, protamine sulfate (0.75 mg/kg) was given intravenously.

Perioperative and Postoperative Anticoagulation
For perioperative anticoagulation, aspirin use was suspended 6 days before surgery except for patients with unstable angina and acute myocardial infarction. Heparin was given by subcutaneous injection until the day before surgery. After surgery, a continuous intravenous infusion of heparin was given starting on the first postoperative day, and oral administration of aspirin was started on the second postoperative day.

Operative and Postoperative Data
Operative and postoperative findings are summarized in Table 2. One hundred fifty-five patients (26.9%) underwent a left anterior thoracotomy approach, and 421 patients underwent a median sternotomy approach. An aortic no-touch procedure [6], in which no surgical manipulation was performed on the ascending aorta, was used in 364 patients (63.2%). Various surgical manipulations were applied to the ascending aorta, including partial aortic clamping in 37 patients (6.4%), use of an automatic proximal anastomosis device (Cardica PAS-Port system, Guidant, Santa Clara, CA) for proximal anastomosis with a saphenous vein in 83 patients (14.4%), and use of an aortic proximal seal system (Heart-String System, Guidant, or Enclose, Novare, Cupertino, CA) in 94 patients (16.3%).


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  		Table 2 Operative and Postoperative Characteristics
 
Postoperative atrial fibrillation was defined as chronic atrial fibrillation and new-onset atrial fibrillation, which was based on duration of atrial fibrillation for more than 15 minutes, detected by telemetry analysis. One hundred twelve patients (19.4%) experienced a new-onset atrial fibrillation within 7 days after surgery.

Postoperative cerebral infarction was defined as the development of a focal neurologic deficit persisting for more than 72 hours. All diagnoses were made by surgical staff, and confirmed by a neurologist and by computed tomography of the brain.

Statistical Analysis
Results for continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed as number (percent). The unpaired Student’s t test was used to compare the continuous variables, and the {chi}2 test was used to compare the categorical variables. Multiple logistic regression analysis was used to test univariate dose-response relationships and multivariate associations for determining risk factors for cerebral infarction within 7 days after surgery. The model using a prespecified set of predictors was selected for multiple logistic regression analysis. Variables were considered for the multivariate models if their univariate probability value was less than 0.20, with the exception of automatic proximal anastomosis devices and the aortic proximal seal system. Independent variables were assigned odds ratios with 95% confidence intervals (95% CI), shown together with the corresponding probability value. A probability value less than 0.05 was considered statistically significant. SPSS version 12.0J software (SPSS Japan, Tokyo, Japan) was used for all analyses.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Ten patients (1.7%) experienced cerebral infarction within 7 days after surgery. The subjects were divided into two groups, those who experienced cerebral infarction after surgery (group C, n = 10) and those who did not (group N, n = 566).

Univariate Analysis Between Group C and Group N
Significant differences were observed between groups with respect to a previous history of cerebral infarction (p < 0.001), preoperative presence of cerebral ischemic symptoms (p < 0.001), vascular lesions in head and neck vessels (p < 0.001), use of partial aortic clamping (p = 0.002), and postoperative atrial fibrillation within 7 days after surgery (p = 0.011; Table 3). Furthermore, tendencies falling short of significance were observed for preoperative atrial fibrillation (p = 0.056), hyperlipidemia (p = 0.067), the number of diseased vessels (p = 0.075), left main stenosis (p = 0.076), unstable angina (p = 0.077), old myocardial infarction (p = 0.082), and aortic no-touch procedure (p = 0.125). Incidence of postoperative cerebral infarction did not change significantly between a left anterior thoracotomy approach and a median sternotomy approach (p = 0.619).


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  		Table 3 Univariate Analysis of Patient Characteristics in the Study Groups
 
Multiple Logistic Regression Analysis
Factors studied in the multiple logistic regression analysis included a previous history of cerebral infarction, preoperative presence of cerebral ischemic symptoms, vascular lesions in head and neck vessels, use of partial aortic clamping, postoperative atrial fibrillation within 7 days after surgery, preoperative atrial fibrillation, hyperlipidemia, the number of diseased vessels, left main stenosis, unstable angina, old myocardial infarction, aortic no-touch procedure, automatic proximal anastomosis devices, and the aortic proximal seal system (Table 4). As a result, the following were confirmed as independent risk factors for cerebral infarction within 7 days after surgery: previous history of cerebral infarction (odds ratio, 26.6; 95% CI, 2.8 to 251.1; p = 0.004), preoperative presence of cerebral ischemic symptoms plus vascular lesions in head and neck vessels (odds ratio, 22.8; 95% CI 1.8 to 285.7; p = 0.015), and use of partial aortic clamping (odds ratio, 11.1; 95% CI, 1.4 to 85.7; p = 0.021). Postoperative atrial fibrillation within 7 days after surgery (odds ratio, 3.4; 95% CI, 0.7 to 16.5; p = 0.121) and preoperative atrial fibrillation (odds ratio, 3.8; 95% CI, 0.6 to 11.7; p = 0.158) were suspected as risk factors for postoperative cerebral infarction. An aortic no-touch procedure and use of an aortic proximal seal system were not risk factors for postoperative cerebral infarction.


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  		Table 4 Multivariate Analysis of Early Postoperative Cerebral Infarction
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
The incidence of postoperative cerebral infarction after off-pump CABG has been reported to range from 0.6% to 3.8% [1–3]. The incidence has been reported to range from 2% to 5% after CABG with cardiopulmonary bypass [7, 8]. There have been no reports indicating superiority of off-pump CABG in reducing the incidence of postoperative cerebral infarction [3]. Because cardiopulmonary bypass is not used with off-pump CABG, any risk of cerebral infarction caused by its use would be avoided. With respect to risk factors for postoperative cerebral infarction in patients undergoing any form of CABG, advanced age [9], diabetes [10], a clinical history of cerebral infarction [11], deterioration of cardiac function [12], and extended cardiopulmonary bypass time [13] have been reported to be correlated. In patients undergoing off-pump CABG, it is often believed that the incidence of cerebral infarction is not reduced by avoiding cardiopulmonary bypass because postoperative infarction is caused by factors that are not preventable. However, cerebral infarction has been reported to develop slightly later after off-pump CABG than after CABG [14], suggesting some general involvement of perioperative factors.

With respect to surgical factors, partial clamping of the ascending aorta was identified as a risk factor in our study. Calafiore and associates [15] reported that in patients undergoing CABG with cardiopulmonary bypass, partial aortic clamping did not add any risk of cerebral infarction but was an independent predictor of stroke when cardiopulmonary bypass was not used. Our results support their conclusion. Chavanon and associates [16] reported that partial clamping of the ascending aorta in off-pump CABG might introduce a risk of aortic dissection, suggesting that partial aortic clamping should be avoided in patients undergoing off-pump CABG. On the other hand, we did not identify use of an automatic proximal anastomosis device for the ascending aorta or an aortic proximal seal system as risk factors for postoperative cerebral infarction. The automatic proximal anastomosis device and the aortic proximal seal system have only recently been introduced in off-pump CABG, and only initial results have been reported. However, the reported frequency of postoperative cerebral infarction with the use of these devices has been low [17–19]; care still should be exercised when choosing the procedure for proximal anastomosis of the ascending aorta to prevent complications other than cerebral infarction. In addition, it is believed that the choice of a proximal anastomosis based on severity of arteriosclerosis in the ascending aorta may be important.

Among the causes of cerebral infarction after cardiac surgery, atrial fibrillation has been cited as the primary factor [13, 20]. Because atrial fibrillation is observed postoperatively in 20% of CABG patients [21], anticoagulation therapy generally is introduced relatively early in off-pump CABG. In the present study, postoperative atrial fibrillation could not be confirmed as an independent risk factor clearly, possibly because of early institution of postoperative anticoagulation therapy. However postoperative atrial fibrillation was suspected as a risk factor for postoperative cerebral infarction (odds ratio, 3.4; 95% CI, 0.7 to 16.5; p = 0.121).

Study Limitations
The present study has a number of limitations. First, subject choice was not randomized and the number of subjects was small. Second, the small number of factors analyzed as postoperative factors might have omitted important considerations from our analysis of risk factors for postoperative cerebral infarction.

Conclusions
Multivariate analysis of factors causing cerebral infarction in early stages after off-pump CABG showed that preoperative symptoms of cerebral ischemia, use of partial aortic clamping, and preoperative history of cerebral infarction were predictive of cerebral infarction. However, an aortic no-touch procedure or an aortic proximal seal system was not confirmed as a factor that increased the risk of early postoperative cerebral infarction.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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  8. Furlan AJ, Sila CA, Chimowitz MI, et al. Neurologic complications related to cardiac surgery Neurol Clin 1992;10:145-166.[Medline]
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  10. Stamou SC, Hill PC, Dangas G, et al. Stroke after coronary artery bypass: incidence, predictors, and clinical outcome Stroke 2001;32:1508-1513.[Abstract/Free Full Text]
  11. Rorick MB, Furlan AJ. Risk of cardiac surgery in patients with prior stroke Neurology 1990;40:835-837.[Abstract/Free Full Text]
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