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CARDIOVASCULAR ANESTHESIA

Echocardiographic and Pathological Evaluation of Atherosclerosis in the Ascending Aorta During Coronary Artery Bypass Grafting

Kumi Matsuyama, MD^*, Tomoko Goto, MD^*, Tomoko Baba, MD^*, Yoshihiro Shibata, MD^*, Yoichiro Otsuka, MD, Ryuzo Sakata, MD, and Hidenori Terasaki, MD^§

Departments of *Anesthesiology, Pathology, Cardiovascular Surgery, Kumamoto Chuo Hospital; and §Department of Anesthesiology, Kumamoto University School of Medicine, Kumamoto, Japan

Address correspondence and reprint requests to Kumi Matsuyama, MD, Department of Anesthesiology, Kumamoto Chuo Hospital, 96 Tainoshima, Tamukaemachi, Kumamoto, 862-0965, Japan.

	Abstract

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We performed intraoperative echocardiography with an epiaortic probe to assess the correlation between echocardiographic appearance and pathological findings of the aorta and to examine the effect of cross-clamping on the aortic wall in 276 patients who underwent coronary artery bypass grafting. The ascending aorta was divided into three segments as follows: lower (L), upper (U), and innominate. The anterior (ant) and posterior (post) intimal thicknesses of each of the three segments were measured. The echogenicity at each of the six locations was examined and was classified as isoechoic or nonisoechoic (hyperechoic, hypoechoic, or mixed type). Tissue punched from the ant L wall of the ascending aorta for vein anastomosis was examined for the presence of atheroma. At the ant L, the prevalence of atheroma was significantly higher in nonisoechoic walls than in isoechoic walls (P = 0.049). We divided patients into two groups according to echogenicity at the U segments. Group A (n = 213) consisted of patients whose echogenicities at both ant U and post U were isoechoic. Group B (n = 63) consisted of patients with nonisoechoic echogenicity at ant U and/or post U. The intimal thicknesses at all six locations in Group B patients were greater than those of Group A (P < 0.01). Deformities at the clamp site after cardiopulmonary bypass were observed significantly more often in Group B than in Group A (P < 0.01). Our data suggest that a nonisoechoic aortic wall indicates more advanced atheroma and a higher risk of deformities at the clamp site. Examination of the echogenicity of the ascending aorta may be one method to reduce perioperative neurological complications.

Implications: We performed epiaortic echocardiography during coronary artery bypass grafting and found that the presence of atheroma and deformities at the cross-clamping site were significantly more prevalent in nonisoechoic walls than isoechoic walls.

	Introduction

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Neurological dysfunction is a serious complication of cardiac surgery, with two well known causes being cerebral hypoperfusion and embolization. Atherosclerotic debris detached from the ascending aorta by palpation, clamping, cannulation, and construction of proximal anastomoses has been recognized as one source of embolization. Accurate evaluation of atherosclerotic lesions in the ascending aorta is therefore important. The evaluation of atherosclerosis by echocardiography has been used as one method to reduce the risk of stroke (1–5). The presence of protruding atheroma has been significantly correlated with stroke (3). The modification of standard cannulation and clamping techniques based on the echocardiographic grading of atherosclerosis might reduce the incidence of stroke (2). In these studies, gradings were assigned according to the wall thickness of the aorta.

In a study using ultrasonic evaluation of the carotid artery, heterogeneous echogenicity was associated with hemorrhage and ulcer in the arterial wall, and a significant correlation between heterogeneous echogenicity and stroke was reported (6). Recently, the correlation between the pathological features and echocardiographic patterns has been studied also in the aortic wall (7,8), and the plaque morphology by imaging techniques has been regarded as important. The purpose of this study was to compare the echogenicity of the ascending aorta with the presence of atheroma and to study the effects of cross-clamping on the aortic wall in patients undergoing coronary artery bypass grafting (CABG).

	Methods

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After approval from the committee on human research of our hospital, we obtained informed consent from 364 consecutive patients who underwent CABG between January 1996 and December 1997. We excluded eight patients who had combined replacement of the ascending aorta and CABG and one patient who underwent minimally invasive direct coronary artery revascularization. Echocardiograph was not performed in three patients because of the emergency nature of the operations. Punch specimens of the aortic wall were not available from 42 patients because the internal mammary arteries were used as the sole conduits for coronary bypass. In the remaining 310 patients, specimens were punched out, but in 34 patients, the specimens were not adequate for microscopic evaluation of the presence of atheroma. Two hundred seventy-six of the 364 patients were thus accepted in the study.

The following four items were evaluated as risk factors for atherosclerosis from history and physical examination: hypertension (history and/or resting blood pressure greater than 150/95 mm Hg and/or antihypertensive therapy), diabetes mellitus (insulin or oral hypoglycemic agents), hyperlipidemia (total cholesterol greater than 240 mg/dL and/or triglyceride greater than 150 mg/dL), and cerebrovascular disease (history of transient ischemic attack or stroke). Abdominal aortic aneurysm (AAA) and peripheral vascular disease (PVD) were also recorded.

Patient Management
Anesthesia was induced with diazepam (5 to 10 mg) and fentanyl (10 to 15 µg/kg) IV. Anesthesia was maintained with 0.4 mg/kg diazepam and 20 µg/kg fentanyl, supplemented with isoflurane. Vecuronium bromide was given as needed to maintain neuromuscular blockade. A membrane or bubble oxygenator was used, and a 40-µm filter was incorporated into the arterial line. The cardiopulmonary bypass (CPB) flow was regulated at 2.0 to 2.4 L · min^-1 · m^-2 with nonpulsatile perfusion. During the bypass period, we regulated the systemic blood pressure pharmacologically using a vasoconstrictor (norepinephrine) or vasodilator (prostaglandin E₁) to maintain mean arterial pressures between 50 and 70 mm Hg, and the rectal temperature between 28° and 32°C. Distal coronary anastomoses and proximal aortic anastomoses were performed during a single aortic cross-clamp.

Evaluation of Atherosclerotic Lesions in the Ascending Aorta
After median sternotomy, the pericardium was divided, and the pericardial cavity was filled with warm saline and an echo probe was placed, directly or with a sterile plastic sheath cover containing saline, on the ascending aorta. We used an ultrasonic imaging system (Sonolayer SSA-260A, HG, Toshiba, Tokyo, Japan) with an epiaortic probe (linear, 7.5 MHz, IOE 702V). The echocardiographic settings were established to optimize imaging of the aortic wall for every patient. The settings were not altered from before to after CPB.

We divided the ascending aorta from the aortic valve to the innominate (lnn) artery into three segments named in order from the heart as follows: lower (L), upper (U), and Inn. After longitudinal images were obtained, each transverse image in the three segments of the ascending aorta was recorded on videotape for precise postoperative analyses. The intimal thickening of each of the six locations was measured by one examiner. Based on the results of the real-time imaging, the necessity for modifications of cannulation, clamping, and proximal graft anastomotic sites and cardioplegia cannula sites was decided by the cardiac surgeon and the anesthesiologist. If the intimal thickness was greater than 3 mm at the sites where the standard operative techniques were planned, the sites were moved to a near-normal area. If there were multiple areas with intimal thickening greater than 3 mm, modifications that included use of the femoral artery or subclavian artery cannulation, no aortic clamping, and/or hypothermic fibrillation and/or hypothermic circulatory arrest was performed.

Part of the anterior aortic wall of the L portion was punched out for the vein graft anastomosis by one cardiac surgeon (RS), and the resulting specimen was microscopically examined for the presence of atheroma. Epiaortic ultrasonography was performed again after CPB to evaluate deformities at the clamp site of the aorta by the same cardiac surgeon who examined the epiaortic images before CPB. After surgery, neurological complications were evaluated by one examiner who was blinded to the echocardiographic findings and modifications of the operative technique. Cerebral magnetic resonance imaging or computed tomography (CT) was performed when necessary. Stroke was defined as a new focal neurological deficit that was confirmed by postoperative magnetic resonance imaging or CT imaging.

Analysis of Echography
The evaluation of echogenicity was performed off-line on video-record tapes. Echogenicity of the intima of the aortic wall was classified in two groups: isoechoic or nonisoechoic (hyperechoic, hypoechoic, and mixed-type) at each of six locations: anterior (ant) L, posterior (post) L, ant U, post U, ant Inn, and post Inn. Isoechoic was defined as uniform echogenicity of a normal intima. Hyperechoic was defined as an area of high echo intensity, greater than that of adventitia. Hypoechoic was defined as an area of low echo intensity (black or speckled grey and black regions) (9,10). Mixed-type was a mixture of two or three of isoechoic, hyperechoic, or hypoechoic. A typical example of a nonisoechoic image is shown in Figure 1. Echogenicity was evaluated independently by two anesthesiologists (KM and TB) who were blinded to pathology and modifications of the operative technique. We used the kappa test to determine the degree of interobserver agreement on the evaluation of echogenicity. The kappa index was 0.936. We discussed our findings and reached agreement in all discrepant cases. We used the Spearman rank correlation coefficient to assess the consistency of interpretation on the echogenicity by each of two observers. The correlation coefficient revealed statistical significance (r = 0.928, P < 0.001 and r = 0.946, P < 0.001).

View larger version (146K): [in this window] [in a new window]   Figure 1. Transverse image of the ascending aorta demonstrating isoechoic (iso), hyperechoic (hyper), and hypoechoic (hypo) echogenicity.

The correlation between echogenicity and the presence of atheroma was analyzed by using Fisher’s exact probability test. The comparisons of the ant and the post intimal thicknesses between each two of three segments were made by using Wilcoxon’s signed rank test. Spearman’s correlation coefficients and P values were calculated between the thickness of the ant L and that of the other five locations.

Because clamping and cannulation were planned at U segments, the patients were divided into two groups according to the echographic findings at U: Group A (n = 213), patients with isoechoic echogenicities at both ant U and post U; Group B (n = 63), patients nonisoechoic at ant U and/or post U. The association between echogenicity and outcomes (deformities at the clamp site or perioperative stroke) was examined by using a logistic regression analysis incorporating the echogenicities at each segment and the preoperative characteristics. The preoperative characteristics were compared between the two groups by using a Wilcoxon’s ranked sum test (for age) and Fisher’s exact probability test. The intimal thicknesses of the aorta were compared between the two groups by using a Wilcoxon’s ranked sum test. The modifications in cannulation and in clamping, deformities at the clamp site, and perioperative stroke were compared between the two groups by using a Fisher’s exact probability test.

P values less than 0.05 were considered statistically significant. All statistical analyses were performed by using SA statistical package, Version 6.12 (SAS Institute, Cary, NC). From an earlier study (10a), we assumed the incidence of deformities at the clamp site in the isoechoic and nonisoechoic groups were 1% and 10%, respectively. A power analysis with = 0.05, ß = 0.20 (power 80%) determined that a sample size of 225 should be adequate.

	Results

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Most patients, 260, were isoechoic at ant L. It was determined that there was atheroma in 44 of these isoechoic patients (16.9%). Atheroma was present in 6 (37.5%) of the 16 nonisoechoic patients. The prevalence of atheroma was significantly higher in nonisoechoic walls than in isoechoic walls (P = 0.049) at ant L.

The intimal thickness of the ascending aorta in our 276 patients is summarized in Table 1. Intimal thickness within the ant and post walls was significantly thicker at Inn compared with U, and U, in turn, was thicker than L. The correlations between the intimal thicknesses of ant L and the other five locations were significant (all five P values less than 0.01). The correlation coefficients ranged from 0.171 to 0.345.

The preoperative characteristics of patients in both groups are shown in Table 2. The Group B patients were significantly older and had a greater incidence of PVD than Group A patients.

Perioperative stroke occurred in five patients (1.8% of total, one in Group A and four in Group B), and the incidence of stroke was significantly greater in Group B than in Group A. In these five stroke patients, four had atheroma at ant L walls. In the four stroke patients of Group B, the intimal thicknesses at the U locations were more than 3 mm, and modifications of cannulation and clamping were performed. Figure 2 shows a representative transverse image of the ascending aorta before and after CPB in one stroke patient in Group B. Although the anterior wall was thick and showed nonisoechoic echogenicity and the cannulation and clamping were displaced, disruption of the surface occurred at the clamp site after CPB. The postoperative cerebral CT of this case showed multiple new infarctions. In one stroke patient of Group A, intimal thicknesses of aorta were less than 2 mm at all six locations, but atheroma was detected at pathologic examination.

View larger version (132K): [in this window] [in a new window]   Figure 2. Left, Intraoperative image showing mixed echogenicity of the aortic wall. Right, Transverse image of the same aorta after cardiopulmonary bypass, demonstrating disruption of the surface of the anterior wall at the clamp site.

	Discussion

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Ohteki et al. (11) reported that atheromatous change was more prevalent in the upper half of the ascending aorta than in the lower half, with a high incidence near the orifice of the Inn artery. In our study, the intimal thicknesses of U and Inn segments were greater than those of L segments. This suggests that atherosclerosis is more likely to develop in the upper parts of the ascending aorta than in the lower, which agrees with the results of Ohteki et al. (11).

We examined the existence of atheroma only in ant L because of restrictions in a human study. The division of patients was performed according to wall echogenicity at U segments because the standard operative techniques involved cannulation and cross-clamping at U. Logistic regression analysis supported the division as appropriate to examine the correlation between echogenicity and the effects of cross-clamping on the aortic wall. The significant differences of intimal thickness, presence of atheroma, and prevalence of nonisoechoic lesions in other locations between the two groups suggested more advanced atherosclerosis in Group B patients.

Comparisons reported between echogenicity and pathological features are more common in the carotid artery (6,9,12–16). Fibrosis is hyperechoic, and calcification is hyperechoic with acoustic shadowing, whereas low-level echoes correspond to hemorrhage (9,14), atheromas rich in cholesterol (14), necrosis, slack connective tissue, and cystic lesion (12). Wolverson et al. (17), who investigated aorta and iliac vessels, reported that dense collagen was highly echogenic, and lipid aggregates were less echogenic. Heterogeneous-type lesions were sometimes a mixture of atheroma and fibrosis (9). Goes et al. (13) reported that newly formed plaques appeared hypoechogenic and homogeneous and became echogenic and heterogeneous. With respect to the correlation between the neurological complications and the echogenicity, lesions that show high echogenicity are rarely associated with cerebral ischemic events (15,16). Reilly et al. (6) reported that heterogeneous plaque was associated with a statistically greater incidence of plaque hemorrhage and ulceration and associated with the patient’s clinical status, transient ischemic, attack, or stroke. In this study (6), ruptures of the intima that might cause neurological complications occurred spontaneously. Even if atherosclerosis of the aorta does not progress to hemorrhage or ulceration, the aortic wall may be liable to rupture during CABG because of the operative procedures, such as clamping and cannulation.

The histological classification of atherosclerosis has been defined by the American Heart Association (18) and has provided a basis for correlation of the composition of lesions with clinical manifestations or with morphology by imaging techniques. According to the classification, a dense accumulation of extracellular lipid, so-called lipid core, is shown in the intima in type IV lesions, and it is not shown in types I through III. Type V lesions are defined as lesions in which prominent new fibrous connective tissue has formed. Type VI is the lesion with surface defect, hematoma-hemorrhage, and/or thrombotic deposit of atheroma. The region between the lipid core and the lesion surface may be susceptible to formation of fissures because it contains proteoglycans and macrophage foam cells, with only isolated smooth muscle cells and minimal collagen (18). Therefore, intima with a lipid core may be prone to disruptions from surgical manipulation.

We decided to modify the standard techniques for the aortic cannulation and clamping based on echocardiography. Clamping of the aorta possibly causes atheromatous embolization. Barbut et al. (19) detected embolic signals in the middle cerebral artery by transcranial doppler ultrasonography during bypass surgery. They reported that many embolic signals were detected immediately after aortic clamp removal, and that there was a correlation between the number of embolic signals and the grade of atheroma of the aortic arch. Wareing et al. (2) reported that modifications of standard cannulation and clamping techniques based on ultrasonic imaging might reduce the frequency of stroke. Our results also indicated the susceptibility to deformities of the atheromatous aorta against cross-clamping. Echocardiography is a more sensitive method to detect atheromatous disease than other methods, including preoperative radiographic studies and intraoperative palpation (1,2,4,11,20). The use of ultrasonic imaging to identify the clamp site is rapid and useful to reduce perioperative stroke caused by embolization of atheromatous debris from the ascending aorta. The protruding mobile plaque or atheroma has been regarded as a cause of stroke (1,3,5). Observation of echogenicity will be one method to detect atheroma that are not protruding but have a risk of stroke.

Although various strategies have reduced the stroke rate, atherosclerosis of aorta remains an important cause of stroke. Our stroke rate (1.8%) was higher than that reported by Wareing et al. (1.0%) (2). The stroke patients in our study underwent displaced aortic clamping or displaced aortic cannulation. As a means to reduce stroke, we should choose the subclavian artery cannulation or nontouch method. In this study, we selected perioperative stroke as an indicator of neurological complication. In further study, we should perform postoperative evaluation of subtle neurobehavioral changes. To describe the correlation between the nonisoechoic wall and neurological complications, the number of patients enrolled should be increased. Our study suggested a correlation of nonisoechoic wall of the ascending aorta with advanced atheroma and with susceptibility to damage by aortic clamping. As one method to judge the necessity for modifications of operative techniques, echogenicity added to the wall thickness of the aorta can provide useful information.

	Acknowledgments

 
The authors thank Mr. Satoshi Kakihara for excellent technical assistance and Dr. Jon Moon for editorial assistance.

	References

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