Arteriosclerosis of the ascending aorta is an important

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1 Aortic Atherosclerosis and Postoperative Neurological Dysfunction in Elderly Coronary Surgical Patients Tomoko Goto, MD, Tomoko Baba, MD, Kumi Matsuyama, MD, Keiko Honma, MD, Masashi Ura, MD, and Takaaki Koshiji, MD Departments of Anesthesiology and Cardiovascular Surgery, Kumamoto Chuo Hospital, Kumamoto, Japan Background. Arteriosclerosis of the ascending aorta is an important risk factor for cerebral embolism. However, the association between arteriosclerosis of the ascending aorta and neurologic dysfunction after coronary artery surgery has not been evaluated prospectively. Methods. We examined whether varying degrees of arteriosclerosis in the ascending aorta, assessed by epiaortic ultrasonography, increased the incidence of neuropsychologic dysfunction and stroke in 463 elderly patients (> 60 years old) after coronary artery surgery. Results. Patients with severe arteriosclerosis (n 76) had higher rates of postoperative neuropsychologic dysfunction (26%) and intraoperative stroke (10.5%); the moderately atherosclerotic patients (n 57) had rates of 7% and 1.8%, respectively; whereas control patients (almost normal or mild arteriosclerosis, n 330) had rates of 8% and 1.2%, respectively (all p < 0.001). Univariate analysis indicated that multiple small infarctions or broad infarctions, cerebral arterial stenosis, circulatory arrest, maximal thickness of intima around the site of aortic manipulation, and deformities due to clamp or cannulation were associated significantly with intraoperative strokes in patients with severe arteriosclerosis. Conclusions. Severe arteriosclerosis of the ascending aorta significantly increased the risk of postoperative neuropsychologic dysfunction and stroke after coronary artery bypass grafting. If a thick plaque is noted near the manipulation site, a nontouch method of the ascending aorta should be applied to reduce the incidence of neurologic dysfunction. (Ann Thorac Surg 2003;75:1912 8) 2003 by The Society of Thoracic Surgeons Arteriosclerosis of the ascending aorta is an important risk factor for cerebral embolism and stroke after cardiac surgery [1,2]. Recently, we demonstrated that the incidence of neurologic dysfunction after coronary artery bypass grafting (CABG) increased significantly in patients who exhibited a higher total atherosclerotic score in the brain, carotid arteries, and ascending aorta [3]. In addition, our previous study revealed that clamp or cannulation induced new lesions of the ascending aorta could be attributed to postoperative stroke [4]. Studies have identified various risk factors for neurologic dysfunction after CABG [5, 6]. Advanced age is often associated with increased aortic arteriosclerosis and is a major risk factor for stroke after cardiac surgery [7, 8]. However, few prospective studies have investigated the association between arteriosclerosis of the ascending aorta and neurologic dysfunction after CABG in elderly patients. The purpose of this study was to further elucidate the relation between arteriosclerosis of the ascending aorta and neurologic dysfunction after CABG and to identify predictors of intraoperative stroke. Accepted for publication Dec 31, Address reprint requests to Dr Goto, Department of Anesthesiology, Kumamoto Chuo Hospital, Tainoshima, Kumamoto , Japan; togoto@bronze.ocn.ne.jp. Patients and Methods Data were collected prospectively on 463 Japanese patients more than 60 years old who underwent elective CABG by a single surgeon at Kumamoto Chuo Hospital between January 1995 and December There were 383 asymptomatic patients who had no history of cerebral stroke or transient ischemic attack, and 80 with a history of stroke or transient ischemic attack. Patients who underwent cardiac valve replacement or ventricular aneurysmectomy were excluded to eliminate the effects of intracardiac air embolism and left ventricular thrombus. We excluded 4 patients who could not be evaluated for the outcomes of neuropsychologic dysfunction and stroke, 2 patients who died in the immediate postoperative period, 1 patient with pulmonary complication, and 1 patient with multiorgan system failure. Demographic and historical data were defined as follows: age, sex, history of hypertension with medication, diabetes mellitus (with medication or strict dietary remedy), hyperlipidemia (total cholesterol 240 mg/dl or triglyceride 150 mg/dl or antihyperlipidemic therapy), renal insufficiency (creatinine 1.9 mg/dl), peripheral vascular disease or abdominal aortic aneurysm, and history of cerebrovascular disease (CVD) with strokes or transient ischemic attack. Informed consent was obtained from all participants, and the study was approved by the medical ethics committees and the institutional review board by The Society of Thoracic Surgeons /03/$30.00 Published by Elsevier Inc PII S (03)

2 Ann Thorac Surg GOTO ET AL 2003;75: AORTIC ATHEROSCLEROSIS AND STROKE 1913 Patient Management and Evaluation of Aortic Arteriosclerosis All operations were performed under standard cardiopulmonary bypass (CPB) and moderate hypothermia (28 to 34 C), as described previously [3]. Although carotid disease was not treated by concurrent carotid endarterectomy, we altered our management of CPB by maintaining a higher pressure ( 70 mm Hg) and slowly rewarming patients with multiple infarctions or severe carotid stenosis. We evaluated atherosclerotic lesions of the ascending aorta by echocardiography (Sonolayer SSA-260A; Toshiba, Tokyo, Japan) using an epiaortic probe (linear, 7.5 MHz, IOE 702V, or PVF-745V) before cannulation and after decannulation. We divided the ascending aorta, from the aortic valve to the innominate artery, into three segments: lower, upper, and innominate (the distal two segments related to aortic clamp and cannulation). After longitudinal images were obtained, each transverse image in the three segments of the ascending aorta was examined on videotape for the precise postoperative analyses (Fig 1). The degree of arteriosclerosis in the ascending aorta was graded according to the modified Wareing s method [10]: 0 (almost normal); 1 (mild, 3-mm intimal thickening); 2 (moderate, 3-mm intimal thickening involving one segment of the ascending aorta); or 3 (severe, 3-mm intimal thickening involving two or all three segments, often with protruding, ulcer of surface, or mobile components). One examiner measured the intimal thickening of anterior or posterior wall of the three segments in all patients. Two observers (T.B. and K.M.) assessed plaque-surface morphology without being aware of the clinical details and modifications to operative technique. Good correlation was apparent, with Spearman rank correlation coefficients (r) of 0.91 and 0.93 for two observers. Overall agreement in findings at plaque-surface morphology and deformities at clamp or cannulation site of aorta were seen in 441 of 456 (97%) and 3 of 121 (98%) images for interobsevers ( 0.86, 0.84). Based on the findings from real-time imaging, the need for modification of cannulation, clamping, proximal graft anastomotic sites, or cardioplegia cannula sites was determined by the cardiac surgeons. If the intimal thickness was greater than 3 mm at sites where the standard operative techniques were planned, the sites were moved to a nearby, relatively normal area. If there were multiple areas with intimal thickening greater than 3 mm, modified techniques were used, such as use of the femoral artery or subclavian artery cannulation, no aortic clamping or hypothermic fibrillation, and hypothermic circulatory arrest. Distal coronary anastomoses and proximal anastomoses were performed during a single aortic cross clamp. Cerebrovascular and Neurologic Evaluation Preoperative cerebrovascular evaluation was performed by cerebral magnetic resonance imaging (MRI), cerebral magnetic resonance angiography (MRA), and cervical MRA in all patients as described previously [3]. Cognitive status was measured using the Hasegawa-dementia score (HDS; score 0 to 30, with 30 best), a modification of the mini-mental state examination, in all patients before operation and on postoperative day 7. Scores less than 24 on the HDS are indicative of cognitive decline (equivalent to 24 on the mini-mental state examination). Postoperative neuropsychologic dysfunction was defined as a decrease in performance from baseline of at least 4 (equal to 2 standard deviations in baseline). Postoperative MRI or computed tomography were performed only on patients with neurologic deficits lasting more than 24 hours or with a decrement of HDS from baseline of at least 8 on postoperative day 7. Patients with new postoperative neurologic symptoms and positive findings on postoperative MRI or computed tomography of the brain were examined by a staff neurologist to confirm intraoperative and postoperative stroke. To assign the stroke subtype, we used a diagnostic algorithm that classified patients as having infarction caused by embolism, infarction caused by hypoperfusion (water-shed infarctions or diffuse hypoxia), or infarction from thrombosis caused by largevessel arteriosclerosis (atherothrombotic stroke). All stroke classifications were reviewed by two independent neurologists who were unaware of the intraoperative findings or modification in operative technique. Statistical Analyses To relate the severity of arteriosclerosis in the ascending aorta to postoperative neuropsychologic dysfunction and stroke, the 463 patients were divided into three groups according to the severity of arteriosclerosis on the ascending aorta: controls (almost normal or mild arteriosclerosis, n 330); moderate arteriosclerosis (n 57); and severe arteriosclerosis (n 76). The three groups were compared statistically using 2 test and one-way analysis of variance. Univariate analysis was performed to identify the risk factors associated with intraoperative strokes induced by aortic manipulation, and with preoperative and intraoperative variables in a subgroup with severe arteriosclerosis. All probabilities were two-tailed, with a p value less than 0.05 regarded as significant. To assess the predictors of severe arteriosclerosis of the ascending aorta, we examined all variables by stepwise logistic regression analysis. Odds ratios (OR) and 95% confidence interval (CI) were calculated for each factor in the presence of the others in the final model. All statistical analyses were completed using a statistical package (version 6.12; SAS Institute, Inc., Cary, NC). Results Of 463 patients studied, 57 patients (12%) had moderate arteriosclerosis and 76 patients (16%) had severe arteriosclerosis. Preoperative and intraoperative characteristics for all patients are summarized in Table 1. Patients with severe arteriosclerosis were more frequently male, and they were more likely to have atherosclerotic risk factors than those in the two other groups. The duration of aortic cross clamping was shorter in the severe arteriosclerosis

3 1914 GOTO ET AL Ann Thorac Surg AORTIC ATHEROSCLEROSIS AND STROKE 2003;75: Fig 1. Ultrasonographic images of the ascending aorta, demonstrating transverse (a, c, and e) and longitudinal scans (b, d, and f). Panels a and b illustrate a normal patient. Panels c and d reveal a moderate arteriosclerosis (arrow). Panels e and f demonstrate typical severe arteriosclerosis (arrow) and ulcerated plaque (arrowhead) of the ascending aorta. (PA pulmonary artery.) group than in the other two groups by modifying operative techniques with reduced proximal anastomoses and aortic clamping. Preoperative cognitive decline and postoperative neurologic complications are presented in Table 2. The group with severe arteriosclerosis had a high rate (26%) of postoperative neurophysiologic dysfunction, moderate arteriosclerosis had a rate of 7%, and control patients had a rate of 8% (p 0.001). Intraoperative stroke occurred in 2.8% of patients overall (13 of 463), with an incidence in patients with severe arteriosclerosis more than nine times that in control patients (p 0.001). In patients with severe arteriosclerosis, 8 patients had intraoperative stroke: 6 caused by emboli and 2 caused by hypoperfusion (diffuse hypoxia, watershed infarction). Postoperative computed tomography or MRI in 6 patients with intraoperative stroke revealed multiple infarctions were probably caused by emboli from disease of the ascending aorta. The outcome of intraoperative stroke resulted in severe disability in 88% of patients (7 of 8) with severe arteriosclerosis, the remaining incident had no serious functional disability. Ten patients with a decrement of HDS from baseline of at least 8 on postoperative day 7 had no new findings on postoperative computed tomography or MRI. Operative mortality was 0.4% (2/463) overall in this study: pump failure in 1 patient and stroke in only 1 patient with severe arteriosclerosis. Although the ascending aorta was cannulated on a relatively normal area identified by ultrasonography in 41 of 76 patients (54%) with severe arteriosclerosis, the remaining patients had an alternate site of arterial cannulation that included the femoral artery (22%) and the subclavian artery (24%). Cross clamp of the ascending aorta was precluded in 28 patients and, in these patients, CABG was performed under hypothermic fibrillation in hypothermic circulatory arrest or on beating heart. No stroke occurred among the 10 patients who underwent CABG by nontouch method to avoid manipulation of the diseased ascending aorta, such as precluding of cannulation, clamping or cardioplegic cannulation, or proximal bypass graft anastomoses. Four of 17 patients (23.5%) with protruding, ulcer of surface, or mobile atheromas had intraoperative stroke compared with 4 of the remaining 59 patients (6.8%) with severe arteriosclerosis of the ascending aorta (p 0.069). In a subgroup with severe arteriosclerosis the preoperative and intraoperative characteristics of the 8 patients with intraoperative strokes and the remaining 68 patients are summarized in Table 3. Further analysis demonstrated that stroke patients were more likely to have had multiple small infarctions or broad infarction and cerebral arterial stenosis (p 0.05). Significant differences were present between stroke and no stroke groups in the intimal thickness of anterior upper and anterior innominate segments, and in technical modification of hypothermic circulatory arrest and deformities of clamp or cannulation site. Deformities of the intima after CPB were mobile components (2 patients with stroke and 1 without stroke) and disruption in 1 patient with stroke. Of four deformities, two were attributed to aortic clamping and the other two to the hole punched out for vein anastomosis or aortic cannulation. In contrast, deformities of the intima after CPB occurred in 2 patients without intraoperative stroke each the groups of control and moderate arteriosclerosis, with more than nine times incidence in patients with severe arteriosclerosis compared with control patients (p 0.011). Stepwise logistic regression analysis of preoperative variables identified carotid stenosis (OR 1.519, 95% CI to 2.272, p 0.042), hypertension (OR 2.281, 95% CI to 4.175, p 0.008), peripheral vascular disease or abdominal aortic aneurysm (OR 2.682, 95% CI to 5.006, p 0.002), and male gender (OR 2.928, 95% CI to 5.886, p 0.003) as independent predictors of severe arteriosclerosis of the ascending aorta. When gender was excluded in improving the best

4 Ann Thorac Surg GOTO ET AL 2003;75: AORTIC ATHEROSCLEROSIS AND STROKE 1915 Table 1. Preoperative and Operative Characteristics of Three Groups a Severe (n 76) Moderate (n 57) Control (n 330) p Value b Age (years) c Age 70 years old 39 (51) 28 (49) 170 (52) Gender (male/female) 65/11 43/14 210/ Hypertension 59 (78) 36 (63) 215 (65) Diabetes mellitus 17 (22) 21 (37) 123 (37) Hyperlipidemia 34 (45) 23 (40) 161 (49) Renal insufficiency 14 (18) 8 (14) 27 (8) PVD 15 (20) 7 (12) 22 (7) AAA 9 (12) 2 (4) 13 (4) History of CVD 13 (17) 15 (26) 52 (16) Stroke/TIA 9/4 9/6 47/5 Number of vessel grafts c Aortic clamp time (min) c CPB time (min) c MRI (brain) Normal or leukoaraiosis 32 (42) 25 (44) 182 (55) Some small infarctions 24 (32) 17 (30) 93 (28) Multiple or broad infarctions 20 (26) 15 (26) 55 (17) MRA (carotid arteries) Normal or mild 60 (79) 49 (86) 304 (92) Moderate 5 (7) 2 (4) 13 (4) Severe or obstruction 11 (14) 6 (11) 13 (4) MRA (cerebral arteries) Normal or mild 59 (78) 48 (84) 279 (85) Moderate 13 (17) 5 (9) 45 (14) Occluded 4 (5) 4 (7) 6 (2) a Values in parentheses represent percentages within group. b The p values refer to comparisons between the three groups. c Expressed as mean standard deviation. AAA abdominal aortic aneurysm; CPB cardiopulmonary bypass; CVD cerebrovascular disease; MRI magnetic resonance imaging; MRA magnetic resonance angiography; PVD peripheral vascular disease; TIA transient ischemic accident. model, the independent predictors of severe arteriosclerosis of the ascending aorta were carotid stenosis (OR 1.630, 95% CI to 2.428, p 0.016), hypertension (OR 1.845, 95% CI to 3.365, p 0.046), peripheral vascular disease or abdominal aortic aneurysm (OR 2.995, 95% CI to 5.565, p 0.001), and renal insufficiency (OR 1.697, 95% CI to 3.465, p 0.147). Comment The incidence of neurophysiologic dysfunction and stroke after CABG was demonstrated to increase in patients who had severe arteriosclerosis of the ascending aorta. Univariate analysis indicated that multiple small infarctions or broad infarctions, cerebral arterial stenosis, circulatory arrest, maximal thickness of the intima Table 2. Postoperative Neurologic Complications of Three Groups a Severe (n 76) Moderate (n 57) Control (n 330) p Value b Preoperative HDS (18) 6 (11) 32 (10) NP dysfunction 20 (26) 4 (7) 27 (8) Intraoperative stroke 8 (10.5) 1 (1.8) 4 (1.2) Emboli/hypoperfusion 6/2 1/0 4/0 Postoperative stroke 1 (1.3) 1 (1.8) 3 (0.9) Emboli/atherosclerosis 1/0 0/1 1/2 Hospital death 1 (1.3) 1 (1.8) a Values in parentheses represent percentages within group. b The p values refer to comparisons between the three groups. HDS Hasegawa-dementia scale; NP neuropsychologic.

5 1916 GOTO ET AL Ann Thorac Surg AORTIC ATHEROSCLEROSIS AND STROKE 2003;75: Table 3. Univariate Analysis for Strokes in Severe Atherosclerosis of Ascending Aorta a Intraoperative Stroke (n 8) No Stroke (n 68) p Value b Age (years) c Male/female 8/0 57/ Renal insufficiency 3 (38) 11 (16) History of CVD 3 (38) 10 (15) Multiple or broad infarctions 4 (50) 16 (24) Carotid stenosis 2 (25) 14 (21) Cerebral arterial stenosis 2 (25) 2 (3) Intimal thickness (mm) c Anterior lower ( ) ( ) Posterior lower ( ) ( ) Anterior upper ( ) ( ) Posterior upper ( ) ( ) Anterior innominate ( ) ( ) Posterior innominate ( ) ( ) Intimal irregularity 5 (63) 25 (37) Protruding, mobile, ulcer 4 (50) 13 (19) Aortic cannulation Ascending aorta 5 (63) 36 (53) Subclavian artery 1 (13) 17 (25) Femoral artery 2 (25) 15 (22) Aortic clamp 4 (50) 44 (65) Circulatory arrest 4 (50) 9 (13) Number of vessel grafts c Number of vein anastomosis c Nontouch of ascending Ao 0 10 (15) Deformity of clamp or cannulation site 3 (38) 1 (1) Hospital death 1 (13) a Values in parentheses represent percentages within group. b The p values refer to comparisons between the two groups. c Expressed as mean standard deviation. Ao aorta; CVD cerebrovascular disease. around the site of aortic manipulation, and deformities due to clamp or cannulation were associated significantly with intraoperative strokes in patients with severe arteriosclerosis. Ascending aortic arteriosclerosis has been noted as a predictor of cerebrovascular events in cardiac surgery patients 50 years old and older screened by epiaortic ultrasound [9]. Increasing age is associated with a higher frequency of ascending aortic arteriosclerosis. In our study of 463 patients, the prevalence of severe arteriosclerosis of 16.4% was consistent with other published rate [10]. Many investigators have reported that cerebral microembolization occurred during CPB, especially aortic cannulation, clamping and declamp [11, 12]. These data suggested that macro or micro debris from the ascending aorta or CPB induced neurophysiologic dysfunction and stroke after CPB [13, 14]. Although our study failed to find an unequivocal relation between cerebral microemboli and neurologic dysfunction, the incidences of neurophysiologic dysfunction and stroke after CABG were significantly higher in patients with severe arteriosclerosis than in the other two groups. In addition, despite minor operative modifications, the maximal thickness of the intima around the site of aortic manipulation and deformity in the ascending aorta after CPB were identified as predictors of intraoperative stroke in patients with severe arteriosclerosis. Because cerebral microembolization and the deformities of the intima were likely caused by aortic clamp, aortic cannulation, or holes punched for proximal anastomoses, these maneuvers should be avoided in patients with predisposing atherosclerotic changes of the ascending aorta. Embolization is the most common cause of intraoperative strokes and is associated with advanced arteriosclerosis in the ascending aorta [9, 10]. In our study the 76 patients with severe arteriosclerosis experienced a 10.5% rate of intraoperative stroke, which was almost consistent with the study by van der Linden and coworkers [15]. They reported that patients with atheromatosis in the ascending aorta had an 8.7% incidence of postoperative stroke, despite minor surgical modifications. Wareing and associates [10] also reported a 6.3% occurrence of strokes in patients for whom only minor modifications had been performed, whereas no stroke occurred among 27 patients with moderate or severe arteriosclerosis who had graft attachment of the aorta using hypothermic circulatory arrest. In this study, one patient with cerebral arteriosclerosis developed diffuse hypoxia after CABG

6 Ann Thorac Surg GOTO ET AL 2003;75: AORTIC ATHEROSCLEROSIS AND STROKE 1917 with hypothermic circulatory arrest. Liddicoat and colleagues [16] also reported that deep hypothermic circulatory arrest increased the risk of postoperative stroke after CABG in octogenarians with a heavily diseased ascending aorta. These data suggests that elderly patients with cerebral arteriosclerosis could not tolerate circulatory arrest. In contrast, no stroke occurred among 10 patients who underwent CABG when alternative techniques were used to avoid manipulation or clamping of the ascending aorta. Although no definite conclusion could be drawn owing to the small number of events, the nontouch method of the diseased aorta may have an advantage in eliminating the source of neurologic dysfunction after CABG. It is difficult to determine the actual origin of emboli in patients with multiple potential sources, such as arteriosclerosis of the ascending aorta, carotid arteries, and cerebral arteries. Of 6 patients with intraoperative stroke, 1 patient had coexisting carotid stenosis and intracranial arteriosclerosis, however his postoperative brain computed tomography revealed multiple infarctions in several cerebral and cerebellar regions; therefore, we determined it was aortogenic embolic stroke. Transcranial Doppler ultrasonography is a useful technique to quantify and detect the source of microemboli during CPB [17]. Continuous monitoring by transcranial Doppler, combined with epiaortic ultrasonography, may help to clarify the pathogenesis of the intraoperative and postoperative cerebral stroke. To determine the source of emboli when cerebral accidents occurred, despite all precautions, the best medical treatment based on radiologic diagnosis should be initiated without delay. Diffusion-weighted MRI demonstrates ischemic lesions quantitatively within early several hours of onset [18] and may provide clues on the association of ischemic lesions in brain and emboli after CABG. Carotid stenosis, hypertension, peripheral vascular disease or abdominal aortic aneurysm, male gender, and renal insufficiency were independent predictors of severe arteriosclerosis of the ascending aorta. Male patients predominated with an 86% incidence of severe arteriosclerosis, even through exclusion of males did not alter the qualitative results. In addition, renal insufficiency became significantly associated with severe arteriosclerosis. These results suggested that the progression of atherosclerotic changes in the ascending aorta were paralleled by advancing arteriosclerosis. Previous studies have demonstrated that endothelial cell nitric oxide synthesis is in downregulated and adhesion molecules are expressed at higher levels on endothelium overlying atherosclerotic plaque [19]. Cardiac surgery with CPB induces a systemic inflammatory response and the sequestration of leukocytes within organ [20]. Recently, off-pump CABG appears to promise elimination of microemboli from the ascending aorta and inflammatory response [21]. Diegeler and coworkers [22] demonstrated a significant difference between conventional and offpump CABG regarding microemboli and postoperative neurophysiologic dysfunction. Further studies should validate, prospectively, whether operative strategies and pharmacologic management with serine protease inhibitors improve neurophysiologic dysfunction and stroke in higher risk patients. Study Limitations Patients with atherosclerotic disease in the ascending aorta, identified by epiaortic ultrasound, had a higher incidence of atherosclerotic disease in the aortic arch and the descending aorta [23]. Although transesophageal echocardiography was not used routinely in the evaluation of patients in this study, we should compare the association of arteriosclerosis between the ascending aorta and descending aorta by transesophageal echocardiography. This study involved a small number of patients for the purpose of identifying predictors for stroke. Further study is needed to determine the relationship between nontouch method of the ascending aorta and stroke. We found an association of arteriosclerosis in the ascending aorta with carotid stenosis, as reported by another study [24]. Further study should investigate whether intimal-media thickening of carotid arteries, demonstrated by cervical ultrasonography, may or may not be useful to detect underlying arteriosclerosis of the ascending aorta in the elderly patients. In conclusion, this study demonstrated that severe arteriosclerosis of the ascending aorta was common and increased the risk of postoperative neurophysiologic dysfunction and stroke in elderly patients undergoing CABG. The main cause of intraoperative stroke seemed to be of embolic, suggesting that macro and microemboli created by surgical maneuvers on the atherosclerotic ascending aorta are highly associated risk factors for brain tissue. Beside actual evaluation of the atherosclerotic plaque in the ascending aorta, we demonstrated several useful predictors to indicate the progression of atherosclerotic changes in the ascending aorta. If thick plaque is noted near the manipulation site, a nontouch method of the ascending aorta should be applied to eliminate the source of neurologic dysfunction after CABG. The authors thank Dr Yasuhiko Matsukado for his critical comments and suggestions, and Dr Jon Moon for his editorial assistance. This work was supported in part by the Okinaka Memorial Institute for Medical Research of Japan. References 1. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. 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