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Do particulate emboli from the ascending aorta in coronary bypass grafting correlate with aortic wall thickness
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     a Innsbruck University Hospital, Innsbruck, Austria

    b St. Antonius Ziekenhuis, Nieuwegein, The Netherlands

    c Karolinska University Hospital, Stockholm, Sweden

    This study was sponsored in part by a research grant from Embol-X.

    Abstract

    This study investigated the previously uncertain relationship of embolic load captured during coronary artery bypass grafting and the extent of ascending aortic atherosclerosis as measured by wall thickness. Patients (n=113) underwent isolated arrested heart coronary artery bypass grafting. Ascending aortic wall thickness measures were obtained by epiaortic ultrasound. Aortic segmental values (distal, mid, proximal) were determined by the summation of measures (anterior lateral, posterior, medial) at each segment. An intraaortic filter (EMBOL-X System, Edwards Lifesciences, Irvine, CA) was placed into the arterial cannula, distal to the aortic measurements, just before releasing the aortic cross-clamp. Particulate debris was found in 96% (109/113) of filters. Mean number of particles was 6.8±4.8 (range 0–23) and mean particle surface area was 5.5±7.0 mm2 (range 0–51 mm2). Total aortic wall thickness, distal third, mid third, and proximal third thicknesses were 27.4±4.4 mm, 9.5±2.0 mm, 9.0±1.9 mm, and 8.8±1.4 mm, respectively. There was no significant correlation between the number of particles or surface area and any of the aortic wall thickness measures. These results suggest that during on-pump, arrested heart coronary artery bypass grafting, embolic load from the ascending aorta is independent of the extent of ascending aortic atherosclerosis in patients with low or moderate risk aortic pathology.

    Key Words: Ascending aorta; Atherosclerosis; Embolism; Extracorporeal circulation; Filter; Coronary artery bypass grafting

    1. Introduction

    Stroke is the most devastating complication in coronary artery bypass grafting (CABG) with an incidence of 1.2–3.0% [1–3]. Emboli originating from various sources are regarded as major causes of injury to the brain. One such source is atherosclerotic material from the ascending aorta. Several studies have demonstrated that ascending aortic atherosclerosis is an independent risk factor for stroke in coronary artery bypass grafting [1,3,4].

    However, scant information is available reporting the relationship between the grade of ascending aortic atherosclerosis and the number of emboli during CABG. Embolism occurring during CABG has been visualized in transesophageal echocardiography (TEE) studies carried out by Barbut and coworkers [5]. Large amounts of embolic signals were detected in these studies, but the definite origin of the emboli remained unclear. In addition, they could not find a clear correlation between the grade of ascending aortic atherosclerosis determined by TEE and the number of emboli.

    Intraaortic filtration enables direct assessment of embolic load during CABG operations. Previous studies have shown considerable amounts of embolic material in aortic filters and atherosclerotic material, most likely originating from the ascending aorta, was detected in 62 to 86% of patients [6,7]. The present study aimed to investigate the type and number of emboli captured in the intraaortic filter and to correlate these measures with the extent of ascending aortic atherosclerosis as determined by epiaortic ultrasound.

    2. Materials and methods

    2.1. Patients

    One hundred and thirteen consecutive patients from three centers underwent isolated CABG with cardiopulmonary bypass (CPB). Eighty-three percent were male and the mean age was 65±10 (range 29–87) years (Table 1). All patients gave informed consent for CABG. Specific ethics committee approval for the use of the Embol-X device was not obtained, because the filter had already received CE mark and was being applied on a routine clinical basis in on-pump cardiac surgery.

    2.2. Ultrasonic assessment of ascending aortic atherosclerosis

    After median sternotomy and graft harvesting, the pericardium was opened and epiaortic sonography was performed using a high frequency linear scanner (Site-Rite IITM Dymax Corp., Pittsburgh, PA). The scanning procedure [4] was carried out in transverse and longitudinal planes to investigate four quadrants (anterior, lateral, posterior, medial) in the proximal, mid, and distal portion of the ascending aorta (Fig. 1). Aortic atherosclerosis was expressed as wall thickness in millimeters. Total wall thickness in each aortic segment (proximal, mid, distal third) was calculated as the sum of wall thicknesses measured in the corresponding four quadrants of each segment.

    2.3. Coronary artery bypass grafting procedure

    After heparinization the distal ascending aorta was cannulated for cardiopulmonary bypass using an EMBOL-X arterial perfusion cannula (EMBOL-X System, Edwards Lifesciences, Irvine, CA). Venous cannulation was performed with a venous two-stage drainage cannula. Ante-grade or retrograde cardioplegia was used according to the preference of the attending surgeon. The ascending aorta was cross-clamped in all patients. A side-biting clamp for performance of the proximal bypass graft anastomoses was used in 85% of patients. Before opening of the aortic cross-clamp an EMBOL-X intraaortic filter was inserted and deployed into the distal ascending aorta through the side port of the arterial perfusion cannula. The filter remained in place throughout the reperfusion period and during performance of the proximal graft anastomoses. Immediately before weaning from cardiopulmonary bypass the filter was removed from the cannula. The filtering device was fixed and stored in formalin, and sent to the histopathology core laboratory where it was further processed.

    2.4. Histologic assessment

    At the central pathology laboratory (Stanford University, Stanford, CA), filters were analyzed by gross visual examination at 10x magnification to determine the quantity (number of particles) and size (surface area of particles) of the captured debris. Sixteen patients were excluded because of incomplete or unavailable histopathology results.

    2.5. Statistical analysis

    Categorical variables are presented as percentages, and continuous variables are given as mean±standard deviation or median and range. Sums of total aortic wall thickness in 12 segments, total thickness in the distal, mid, and proximal aorta, maximum value in each quadrant (anterior, lateral, medial, posterior) and each location (distal, mid, proximal) of the ascending aorta were correlated with the number of particles captured and the surface area covered in the filters. Other independent variables evaluated were gender, age, preoperative status (elective or urgent), presence or absence of atherosclerosis (aortic wall thickening or calcification on TEE), number of times partial clamp applied, number of proximal anastomoses, preoperative NYHA (New York Heart Association) class (I/II or III/IV) and preoperative EuroSCORE. Bivariate analyses were performed with Pearson correlation after log transformation of the data and were included in a multiple linear regression model at P<0.15 (SPSS 12.0.1, Chicago, IL). Statistical significance was anticipated at a P<0.05.

    3. Results

    Demographic and perioperative data are presented in Table 1. Atherosclerosis as determined by TEE was present in 31% of patients. Table 2 shows the distribution of wall thickness in the four quadrants of the proximal, mid, and distal third of the ascending aorta (Fig. 1). Total wall thickness of all quadrants (12 segments) was 27.4±4.4 mm (range 23–43 mm) and the maximum aortic wall thickness of 12 segments was 3.1±1.0 mm (median 3 mm; range 2–5 mm). The maximum thickness by aortic third location was 10.0±2.2 mm (median 10 mm; range 8–17 mm) and the maximum thickness by quadrant was 7.7±1.9 mm (median 7 mm; range 6–15 mm). As can be seen in Table 2, the predominant site of aortic wall thickening was in the posterior quadrant and the distal third of the ascending aorta.

    The median number of particles captured in the filters was 6 (6.8±4.8) and the median surface area covered by particulate was 3.3 mm2 (5.5±7.0). Particulate debris was captured in 96% of filters and the material primarily consisted of fibrous atheroma (95%). Table 3 shows further components of the filter content.

    As shown in Fig. 2, no significant correlation was found between the number of particles captured and total aortic wall thickness, maximum aortic wall thickness of 12 segments, or the proximal, mid, and distal third of the ascending aorta. There was a similar lack of correlation between the surface area of embolic material captured and any of the aortic wall measures.

    There was a weak but significant correlation between the number of particles and EuroSCORE (r=0.272, P=0.004), NYHA class (r=–0.378, P<0.0001), the number of proximal anastomoses (r=0.274, P=0.004), and preoperative status (r=–0.200, P=0.036) (Fig. 3). Multivariable regression analysis showed NYHA class III or IV (standardized coefficient=–0.25, P=0.025) to be the best independent predictor of the number of particles. The regression model (R=0.389, adjusted R2=0.118, P=0.002) explained only 12% of the particles captured in the aortic filters (Table 4).

    4. Discussion

    Our study demonstrates that the majority of emboli captured by intraaortic filtration during CABG consist of fibrous atheroma, confirming the ascending aorta as the source of emboli. However, increased ascending aortic wall thickness in CABG patients is not necessarily associated with an increased amount of emboli released into the aortic blood stream. Analysis of intraaortic filters showed that large amounts of embolic material may be found in patients with normal ascending aortas, whereas little embolic material may be detected even in the presence of a markedly thickened ascending aorta. This finding is astonishing but in accordance with findings by Barbut and coworkers who demonstrated that the number of emboli released into the ascending aorta in TEE studies is increased in patients with perioperative strokes without finding a correlation with the grade of aortic atheroma [5]. In these investigations the type of emboli could not be differentiated but definitely no correlation with the grade of atheroma was found. In a recent study by Martens and colleagues there was a significantly greater amount of debris captured during the anastomotic procedure (whether by aortic connector or partial clamp and conventional anastomoses) than after release of the aortic cross-clamp, suggesting the anastomoses itself is a major factor in embolic release [8]. In contrast to these results, Hammon and coworkers, using transcranial Doppler (TCD), reported significantly more embolic signals during CABG in patients with a diseased ascending aorta [9].

    Aortic manipulation by the aortic cross-clamp, a partial occluding clamp, punching devices, and suturing instruments are thought to mobilize material from the aortic wall. Signals detected on TEE or TCD studies may be of both gaseous and particulate origin, and differentiation between the two types is difficult. In our study using intraaortic filtration we were able to directly capture and analyze the quantity and quality of particles released from the ascending aorta. Gaseous emboli, which may blur investigations in studies utilizing TEE, were excluded in our examinations. Moreover, we selected CABG patients to minimize particulate generation from cardiac structures other than the aortic wall. We used epiaortic ultrasound as a means to quantify ascending aortic wall pathology. As a noninvasive intraoperative method, this ultrasonic examination seems to gain acceptance for detection of ascending aortic disease [10]. Studies using epiaortic ultrasound have repeatedly correlated perioperative morbidity and mortality with the degree of this pathology [11,12]. We found plaques primarily in the posterior distal aorta, though previous reports showed a predominance of plaques in the middle and lateral portions of the aorta [4,13].

    The ICEM (International Council of Emboli Management) studies found that embolic material captured by intraaortic filtration during coronary surgery primarily consists of fibrous atheroma and platelet/fibrin deposits [6,14]. Our study involving only CABG confirmed this. Also, the number of particles and surface area of embolic material were similar. The main origin of the atheromatous material was likely the ascending aorta.

    Does the lack of correlation between ascending aortic wall thickness and number or surface area of embolic particles hold therapeutic implications It seems to indicate use of filtration devices in all cardiac operations. A prospective randomized trial has recently demonstrated that intraaortic filtration significantly reduces renal failure, though not stroke, after cardiac surgery [7].

    A previous study using multivariable analysis in 40 consecutive patients undergoing CABG showed the presence of plaque in the ascending aorta to be related to the number of particles captured by intraaortic filtration together with hypertension, obesity and the number of proximal anastomoses [15]. In this study probably more patients with severe atherosclerosis of the ascending aorta were included, and a different method to grade atherosclerotic pathology. In the present study, in a larger patient population using detailed correlation models, the number of particles in the filters was independent of aortic wall thickness; in multivariate analysis, ascending aortic wall thickness did not predict the occurrence of particulate embolism. The number of proximal anastomoses correlated with number of particles in our bivariate analysis but dropped out in the multivariate model.

    4.1. Limitations of the study

    A limitation of the current observations is that the sample size is probably small. As opposed to common clinical anticipation, no correlation between ascending aortic wall thickness and embolic load during CABG could be found. One reason for this finding may also be the fact that the measurements in this study were not sufficiently sensitive to detect correlations. Another factor could be that there is no linear association between ascending aortic wall thickness and number of emboli detected in the filters. There was a bias in our patient population toward low-grade ascending aortic atherosclerosis, resulting in limited aortic pathology. Patients with markedly thickened ascending aortas were only rarely included. In cases of severe pathology at all three participating centers, aortic no-touch concepts such as OPCAB combined with extra-anatomical bypass graft variations were selected. It can also be questioned whether ascending aortic wall thickness is a reasonable marker of ascending aortic atherosclerosis. The St. Louis Group, which has extensive experience with epiaortic scanning, also used ascending aortic wall thickness to differentiate between mild, moderate, and severe forms of ascending aortic atherosclerotic disease [11].

    4.2. Study conclusions

    Our study suggests that particulate emboli captured from the ascending aorta during on-pump coronary artery bypass grafting do not clearly correlate with ascending aortic wall thickness and pathology in patients with mild to moderate ascending aortic atherosclerosis.

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