Rob G.A. Ackerstaff

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).

OBJECTIVES In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.

The significance of microemboli detection by means of transcranial Doppler ultrasonography monitoring in carotid endarterectomy

PURPOSE Carotid endarterectomy (CEA) performed with continuous transcranial Doppler monitoring provides a unique opportunity to determine the number of cerebral microemboli and to relate their occurrence to the surgical technique. The purpose of this study was to assess in CEA the impact of cerebral microembolism on clinical outcome and brain architecture. We also evaluated the influence of the audible transcranial Doppler signal on the surgeon and his or her technique. METHODS In a prospective series of 301 patients, CEA was monitored with electroencephalography and transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. Preoperative and intraoperative risk factors were entered in a logistic regression analysis program to assess their correlation with cerebral outcome. To evaluate the impact of cerebral microembolism on brain architecture, we compared preoperative and postoperative computed tomography scans or magnetic resonance images of the brain in two subgroups of 58 and 40 patients, respectively. RESULTS Seven (2.3%) patients had intraoperative transient ischemic symptoms, three (1%) had intraoperative strokes, 1 (0.3%) had transient ischemic symptoms after operation, and 10 (3.3%) had postoperative strokes. Four (1.3%) patients died. Microemboli (> 10) noticed during dissection were related to both intraoperative (p < 0.002) and postoperative (p < 0.02) cerebral complications. Microemboli that occurred during shunting were also related to intraoperative complications (p < 0.007). Microembolism never resulted in new morphologic changes on postoperative computed tomography scans. On the contrary, the phenomenon of more than 10 microemboli during dissection was significantly (p < 0.005) related to new hyperintense lesions on postoperative T2-weighted magnetic resonance images. CONCLUSIONS During CEA the presence of microembolism (> 10 microemboli) during dissection shows a statistically significant relationship with perioperative cerebral complications and with new ischemic lesions on magnetic resonance images of the brain. Moreover, microembolism during shunting is also related to intraoperative complications. Surgeons can be guided by the audio Doppler and emboli signals by changing their technique. This change may result in a decrease of microembolism and consequently in a decline of the intraoperative stroke rate.

Impact of microembolism and hemodynamic changes in the brain during carotid endarterectomy.

Background and Purpose Monitoring of carotid endarterectomy with electroencephalography and transcranial Doppler ultrasonography provides instantaneous information about hemodynamic changes and embolic signals. However, a relation between these findings and intraoperative infarcts has not yet been demonstrated. Methods In this study we compared preoperative and postoperative computed tomographic scans (58 patients) or magnetic resonance imaging (40 patients) of the brain, assessed by two independent observers, to detect intraoperative infarcts, and we related any such new lesions to the findings of intraoperative monitoring. Results In the computed tomography series one intraoperative infarct occurred, with corresponding clinical deficits. In the magnetic resonance group four patients developed new lesions that occurred intraoperatively, all of which were clinically silent. There was a significant relation between the number of embolic signals during the surgical dissection of the carotid artery and the occurrence of intraoperative infarcts (P<.005). Three of the four infarcts were of the lacunar type; the fourth patient had a border-zone infarct, associated not only with many embolic signals but also with low flow during cross-clamping. There were no demonstrable ultrasound side effects on brain tissue. Conclusions Embolic signals detected by transcranial Doppler monitoring in the dissection phase of carotid endarterectomy show a significant relation to new ischemic lesions and therefore are potentially harmful. The phenomenon should alert the vascular surgeon.

Site and pathogenesis of infarcts associated with carotid endarterectomy.

We analyzed perioperative strokes in 658 carotid endarterectomies with the purpose of explaining the pathogenesis from the morphologic aspect of the infarct on cerebral computed tomograms. All endarterectomies were performed with continuous electroencephalographic monitoring. Of the 42 ischemic strokes (6.4% of all endarterectomies), 34 could be studied. Seven infarcts were hemodynamically induced (five watershed infarcts, two patients with bilateral ischemia); all seven occurred during surgery. Twenty-three of the remaining 27 infarcts were within the territory of the middle cerebral artery (20) or anterior cerebral artery (three) and were probably of thromboembolic origin; 13 of these 23 occurred during surgery (57%). If intraoperative stroke was heralded by permanent electroencephalographic changes, these were not related to the moment of cross-clamping. In four patients the computed tomogram was normal. We believe these facts favor the hypothesis that thromboembolism is the most important factor in the pathogenesis of perioperative stroke associated with carotid endarterectomy under conditions of optimal cerebral monitoring.

Carotid endarterectomy with transcranial Doppler and electroencephalographic monitoring. A prospective study in 130 operations.

Background and Purpose We report the results of combined recording of hemodynamic and thromboembolic phenomena during carotid endarterectomy by means of computerized electroencephalography as well as transcranial Doppler ultrasonography. The study focuses on the additional value of transcranial Doppler to detect ischemia during surgery. Methods Combined monitoring was performed in 130 consecutive operations, using standard anesthe-siological, surgical, and neurophysiological procedures. Results A reduction of ≥70% of blood flow velocities in the middle cerebral artery during cross-clamping was measured in 16 patients. In seven of these cases there were no severe electroencephalographic changes and a shunt was not used, but one of the patients developed a subcortical infarct with slight disability. In 55 patients, 75 episodes of embolization were detected by transcranial Doppler. In one of these, with massive embolization after release of the clamp, an intraoperative stroke occurred without changes on cranial computerized tomography or neurological disability on follow-up. In the other 54 patients, intraoperative embolization did not cause clinical or neuroradiological symptoms. Electroencephalographic changes occurred in only two of the 75 episodes. In addition to the two nondisabling strokes during surgery (1.5%), six strokes occurred within 5 days of operation, including one hemorrhage. There was no significant relation between contralateral carotid occlusion and stroke (p=0.6). Conclusions During carotid endarterectomy, transcranial Doppler immediately provides information about thromboembolism and hemodynamic changes that are not detected by electroencephalography alone. Acoustic feedback from the transcranial Doppler monitoring unit has a direct influence on the surgical technique. Transcranial Doppler ultrasound may be a useful tool in the study and prevention of intraoperative stroke.

Detection of Cerebral Microemboli by Means of Transcranial Doppler Monitoring Before and After Carotid Endarterectomy

BACKGROUND AND PURPOSE The main purpose of carotid endarterectomy (CEA) for neurologically symptomatic high-grade extracranial carotid artery stenosis is to remove the suspected source of cerebral microemboli. Transcranial Doppler (TCD) ultrasonography has the potential for detecting solid microemboli in the basal cerebral arteries. Therefore, TCD monitoring provides the opportunity to assess the rate of microemboli to the brain in patients with symptomatic high-grade carotid artery stenosis and to verify whether these phenomena have ceased after CEA. METHODS TCD monitoring was performed in 41 patients to detect high-intensity transient signals indicating microemboli in the middle cerebral artery before and after CEA. In the event that, within 1 week after CEA, TCD monitoring revealed ongoing cerebral microemboli on the side of surgery, the examination was repeated 3 months later. RESULTS High-intensity transient signals were detected preoperatively on the side of the affected carotid artery in 22 patients (54%; mean, 10.2 per hour; range, 1 to 88). Linear regression analysis demonstrated a trend toward an inverse relationship between the number of high-intensity transient signals per hour and the time interval since the last episode of neurological symptoms (P < .1). CEA resulted in a significant reduction in the number of high-intensity transient signals per hour 7 days after surgery (mean, 6.0 versus 0.4 per hour; median, 0 versus 0; n = 37; P < .005) and 3 months later (mean, 6.3 versus 0 per hour; median, 1.3 versus 0; n = 41; P < .0001). CONCLUSIONS Clearly, TCD monitoring can be helpful in assessing the effect of CEA in removing the suspected source of cerebral microemboli. Ongoing microemboli to the brain should prompt reassessment of the operated carotid artery or a search for other potential sources of cerebral embolism. Carotid artery plaques seem to produce cerebral microemboli for a limited period, which implies that the prophylactic effect of CEA might decrease if the operation is delayed.

Atherosclerotic Plaque Composition and Occurrence of Restenosis After Carotid Endarterectomy

CONTEXT Previous studies have assessed the predictive value of clinical and angiographic parameters for development of restenosis after vascular interventions. The composition of the atherosclerotic plaque at the intervention site has had limited evaluated as a marker for restenosis [corrected]. OBJECTIVE To investigate the relationship between atherosclerotic plaque histology and the occurrence of restenosis after carotid endarterectomy. DESIGN, SETTING, AND PATIENTS The Athero-Express study is a longitudinal vascular biobank study that includes the collection of atherosclerotic plaques of patients undergoing primary carotid endarterectomy. Five hundred patients were prospectively followed up between April 1, 2002, and March 14, 2006, to assess carotid artery restenosis measured by duplex ultrasound 1 year after the intervention. MAIN OUTCOME MEASURES Risk of carotid restenosis in relation to predefined histological characteristics (macrophage and smooth muscle cell infiltration, collagen, calcifications, intraplaque bleeding, luminal thrombus, and lipid core size), adjusted for clinical characteristics (multivariate logistic regression analysis). RESULTS At 1 year, 85 patients (17%) developed 50% or greater restenosis, including 40 patients (8%) who developed 70% or greater restenosis of the target vessel. Patients whose histological examination of the plaque revealed marked macrophage infiltration (n = 286) had a lower risk than those with none or minor macrophage infiltration (n = 214) of developing 50% or greater restenosis (risk difference, 11.5% vs 24.3%; adjusted odds ratio [OR], 0.43; 95% confidence interval [CI], 0.26-0.72) and a lower risk of developing 70% or greater restenosis (risk difference, 4.5% vs 12.6%; adjusted OR, 0.36; 95% CI, 0.17-0.74). Patients (n = 177) with a plaque having a large lipid core size (>40%) had a lower risk than those (n = 94) with a plaque having a lipid core size of less than 10% of developing 50% or greater restenosis (risk difference, 11.3% vs 25.5%; adjusted OR, 0.40; 95% CI, 0.19-0.81) and a lower risk of developing 70% or greater restenosis (risk difference, 5.6% vs 14.9%; adjusted OR, 0.42; 95% CI, 0.17-1.04), independent of clinical characteristics. CONCLUSIONS Plaque composition is an independent predictor of restenosis after carotid endarterectomy. The dissection of a lipid-rich, inflammatory plaque is associated with reduced risk of restenosis.

Staged Carotid Angioplasty and Stenting Followed by Cardiac Surgery in Patients With Severe Asymptomatic Carotid Artery Stenosis Early and Long-Term Results

Background— The strategy for treating patients with severe asymptomatic carotid artery stenosis and cardiac disease remains unresolved. Staged or combined carotid endarterectomy in these patients offers the potential benefit of decreased neurological morbidity during and after cardiac surgery; however, in high-risk patients with severe coronary artery disease, chronic obstructive pulmonary disease, or renal impairment, the incidence of death and stroke is significantly higher. Methods and Results— We report the results of a prospective, single-center study designed to evaluate the feasibility and safety of carotid artery angioplasty and stenting (CAS) before cardiac surgery in neurologically asymptomatic patients. The periprocedural and long-term outcomes of 356 consecutive patients who underwent CAS before cardiac surgery were analyzed. The procedural success rate of CAS was 97.7%. The death and stroke rate from time of CAS to 30 days after cardiac surgery was 4.8% (n=17). The myocardial infarction rate from time of CAS to 30 days after cardiac surgery was 2.0% (n=7), and the combined death, stroke, and myocardial infarction rate was 6.7% (n=24). Distal embolic protection devices were used in 40% of the cases. Conclusions— This large cohort of asymptomatic patients who underwent staged CAS and cardiac surgery experienced a low periprocedural complication rate. The high rate of freedom from death and stroke during the 5 years of follow-up supports the long-term durability of this approach. Our findings suggest that this new strategy may become a valuable alternative in the treatment of patients with combined carotid and cardiac disease.

Prediction of Intracerebral Haemorrhage after Carotid Endarterectomy by Clinical Criteria and Intraoperative Transcranial Doppler Monitoring: Results of 233 Operations

OBJECTIVE Identification of predictors of intracerebral haemorrhage after carotid endarterectomy. DESIGN Retrospective comparison of patients who developed intracerebral haemorrhage and patients who did not, with special attention to intraoperative transcranial Doppler monitoring of the ipsilateral middle cerebral artery and postoperative signs and symptoms of hypoperfusion. SUBJECTS AND MATERIALS Two-hundred and thirty-three patients were studied with regard to the increase of peak blood flow velocities and pulsatility indices after endarterectomy and to the occurrence of unilateral throbbing headache or hypertension. RESULTS Intracerebral haemorrhage occurred in five cases. Seventeen patients complained of headache or showed hypertension, four of whom developed an intracerebral haemorrhage (p < 0.001; Fishers exact test). The positive predictive value of headache, hypertension, or both, was 24% (diagnostic gain 22%). The negative predictive value, sensitivity and specificity were 99, 80 and 94%, respectively. The increase of peak blood flow velocities and pulsatility indices in patients who developed intracerebral haemorrhage was significantly higher than in patients who did not (p < 10(-5); one-way ANOVA). When cut-off levels for the increase of peak blood flow velocities and pulsatility indices were set to 175 and 100%, respectively, the positive predictive value of intraoperative transcranial Doppler was 100% (diagnostic gain 98%). The negative predictive value, the sensitivity and specificity were 99, 80 and 100%, respectively. CONCLUSION An increase of peak blood flow velocity > or = 100% or pulsatility index > or = 100% after declamping predicts intracerebral haemorrhage more accurately than the occurrence of headache or hypertension. Transcranial Doppler monitoring can be used to identify patients at risk for intracerebral haemorrhage, in whom control of blood pressure and modest degrees of anticoagulation may be appropriate.

Continuous Transcranial Doppler Ultrasonography and Electroencephalography During Carotid Endarterectomy: A Multimodal Monitoring System to Detect Intraoperative Ischemia

Transcranial Doppler ultrasonography (TCD) and EEG monitoring during carotid endarterectomy provide continuous information on the electrical activity of the cerebral cortex, blood flow velocities in the ipsilateral middle cerebral artery, and the occurrence of microemboli. One hundred thirty carotid endarterectomies performed with TCD and EEG monitoring were studied prospectively. During cross-clamping of the carotid artery a high correlation was found between EEG asymmetry and reduction of blood flow velocity in the middle cerebral artery (p<10−6, Studentst test). Microemboli were detected in 80 patients during the operation. Although not statistically significant, this occurrence of microemboli was associated with signs and symptoms of intraoperative ischemia (p=0.08, Fishers exact test). In comparison with earlier studies, a tendency toward intraoperative stroke reduction was noted. Only one nondisabling intraoperative stroke occurred (0.8%). In addition to the EEG, TCD monitoring of hemodynamic changes and microemboli in the middle cerebral artery provides important information to the surgeon instantaneously. TCD monitoring of blood flow velocities and embolism during carotid endarterectomy may help to reduce the number and gravity of intraoperative stroke.