Hemodynamic effect of carotid stenting and carotid endarterectomy

Transcription

1 Hemodynamic effect of carotid stenting and carotid endarterectomy Peter Jan van Laar, MD, a Jeroen van der Grond, PhD, b Frans L. Moll, MD, PhD, c Willem P. Th. M. Mali, MD, PhD, a and Jeroen Hendrikse, MD, PhD, a Utrecht and Leiden, The Netherlands Background: Carotid angioplasty with stent placement (CAS) may offer an alternative treatment to carotid endarterectomy (CEA). However, in contrast to CEA, which has been shown to normalize impaired cerebral hemodynamics, the effects of CAS remain unclear. To investigate alterations in cerebral hemodynamics, we prospectively studied patients undergoing CAS and compared them with a group of similar patients undergoing CEA. Methods: Twenty-three patients undergoing CAS for recently symptomatic internal carotid artery (ICA) stenosis were prospectively studied. Volume flow in the ICAs and basilar artery (BA) were measured with magnetic resonance volume flow quantification before CAS and 1 month after. The results were compared with those in 13 similar patients undergoing CEA and 40 control subjects without ICA stenosis. Results: After CAS, volume flow in the ipsilateral ICA increased from to ml/min (P <.001), and total volume flow (ICAs plus BA) increased from to ml/min (P <.05). No significant changes were seen in the contralateral ICA and BA after CAS. Total volume flow and flow in the stenosed ICA normalized after CAS compared with control subjects. Volume flow values similarly improved after CEA. Conclusions: CAS results in a normalization of impaired cerebral hemodynamics, as assessed by magnetic resonance volume flow measurements. The degree of improvement is similar to that seen after CEA. (J Vasc Surg 2006;44:73-8.) In patients with symptomatic severe internal carotid artery (ICA) stenosis, carotid endarterectomy (CEA) has 1,2 been shown to result in a significant stroke reduction. The favorable effect of surgery is assumed to be based on the removal of the atheromatous plaque, which can be a source of cerebral emboli. Moreover, it has been suggested that improvement of blood flow after CEA may further decrease stroke risk by a better wash out of cerebral emboli. 3 Carotid angioplasty with stent placement (CAS) has emerged as a potential therapeutic alternative to CEA for the treatment of high-grade ICA stenosis. Currently, several major trials directly comparing CAS with CEA are underway. 4 Unlike CEA, CAS does not remove the atheromatous plaque. CEA has previously been shown to restore blood flow distribution and normalize impaired cerebral hemodynamics. 5,6 However, the hemodynamic effects of CAS on the treated ICA and the collateral artery blood flow remains unclear. Magnetic resonance (MR) flow quantification is a fast, safe, and noninvasive method to determine blood volume flow (ml/min) in the major brain-feeding arteries. 5-8 To investigate alterations in cerebral hemodynamics, we performed a prospective study of MR flow measurements in patients with symptomatic ICA stenosis From the Departments of Radiology at the University Medical Center Utrecht, a and Leiden University Medical Center, b and the Department of Vascular Surgery, University Medical Center Utrecht. b Competition of interest: none. Reprint requests: Peter Jan van Laar, MD, University Medical Center Utrecht, Department of Radiology (Hp E01.332), PO Box 85500, 3508 GA Utrecht, The Netherlands ( p.j.vanlaar@azu.nl) /$32.00 Copyright 2006 by The Society for Vascular Surgery. doi: /j.jvs before and after CAS and compared them with a group of similar patients undergoing CEA. METHODS Subjects. The study was conducted between November 2004 and November 2005 and included 36 consecutive patients (24 men, 12 women), with a mean ( SD) age of 67 9 years and ICA stenosis ( 50% diameter reduction), who had been symptomatic in the previous 12 weeks. All patients were participants of the International Carotid Stenting Study, a randomized controlled trial to compare CEA and CAS. Patients had to be suitable both for CAS and surgery. Patients who had a stroke causing major 9 disability (modified Rankin score 3 to 5) were excluded. The ethics committee of our institution approved the study protocol, and written informed consent was obtained from all participants. All patients underwent contrast-enhanced MR angiography (CE-MRA) and duplex ultrasonography. Grading of stenosis in the ICA was performed with CE-MRA according to North American Symptomatic Carotid Endarterectomy Trial criteria. 10 None of the patients had intracranial steno-occlusive disease on CE-MRA. CAS was performed in 23 patients (16 men, 7 women; age, 68 9 years) and 13 patients underwent CEA (8 men, 5 women; age, years). The number of CAS patients is higher than the number of CEA patients because the MR volume flow investigations in patients randomized to CEA were added to the study protocol 5 months after starting this investigation in patients randomized to CAS. In the CAS group, the mean SD degree of stenosis in the ipsilateral ICA was 79% 12% and 37% 30% in the contralateral ICA. In the CEA group, the degree of stenosis in the ipsilateral ICA was 82% 12% and 32% 21% in the 73

2 74 van Laar et al JOURNAL OF VASCULAR SURGERY July 2006 Fig 1. Sagittal localizer magnetic resonance (MR) angiogram illustrates the positioning of a two-dimensional phase-contrast MR section to measure the volume flow through the internal carotid arteries and basilar artery in a patient with symptomatic stenosis of the right internal carotid artery. contralateral ICA. The degree of stenosis in the ipsilateral ICA after CAS was 2% 4% and 3% 7% after CEA. All operations and CAS procedures were uncomplicated. The control group consisted of 30 subjects (20 men, 10 women; age, 67 7 years) matched for age and sex, without abnormalities on MR imaging and MRA of the brain and without ICA stenosis on duplex ultrasonography. These subjects were treated in the department of neurology for diseases other than intracranial diseases and had no history of ischemic neurologic deficits. Magnetic resonance angiography. The MR investigations were performed 1 day before and 1 month (range, 28 to 36 days) after carotid intervention on a 1.5 T wholebody system (Gyroscan ACS-NT, Philips Medical Systems, The Netherlands). On the basis of two MR localizer scans in the coronal and sagittal plane, a two-dimensional phasecontrast (2D PC) MR section was positioned at the level of the skull base to measure the volume flow in the ICAs and the basilar artery (BA). Fig 1 illustrates the positioning of the 2D PC section through the ICAs and the BA (TR, 16 milliseconds; TE, 9 milliseconds; flip angle, 7.5 ; field of view, mm; matrix, ; section thickness, 5 mm; average, 8; velocity sensitivity, 100 cm/s). Data processing and statistical analysis. On an independent workstation, quantitative volume flow values were calculated in the ICAs and BA by integrating across manually drawn regions of interest that closely enclosed the vessel lumen. The side of the treated ICA was designated the ipsilateral side and the nontreated side, the contralateral side. Total volume flow was defined as the sum of the ICAs and BA volume flow. Differences in volume flow between baseline and 1 month after carotid intervention were analyzed with paired sampled t test. Differences in volume flow between patients undergoing CAS and patients undergoing CEA, between patients and control subjects, and between the ipsilateral and the contralateral hemisphere were analyzed with Student s t test. P.05 was considered significant. For statistical analysis, SPSS (SPSS, Inc, Chicago, Ill) for Windows (Microsoft, Redmond, Wash) was used. Volume flow data are expressed as mean standard error of the mean (SEM). RESULTS Fig 2 shows the intra-arterial cerebral angiography and MR volume flow images of a 52-year-old patient with transient ischemic attacks associated with a right-sided ICA stenosis. The cerebral angiograms demonstrate that the 90% stenosis, located proximal in the right ICA, is redressed after CAS. The MR flow quantification study of the individual ICAs and BA at the level of the skull base before CAS showed a volume flow of 55 ml/min through the stenosed right ICA. After CAS, flow through the treated ICA increased to 221 ml/min. Fig 3 shows the changes in ipsilateral ICA flow after CAS and CEA for all individual patients. Before CAS, a volume flow of ml/min was measured in the ipsilateral ICA. After CAS, the volume flow in the ipsilateral ICA significantly increased ( ml/min; P.001). In patients undergoing CEA, volume flow in the ipsilateral ICA ( ml/min) also significantly increased postoperatively ( ml/min; P.001). No significant difference in flow increase in the ipsilateral ICA was found between patients who had CAS and those who had CEA. Furthermore, no significant changes were seen in the contralateral ICAs and BA after CAS or CEA. Fig 4 displays the increase in volume flow in the ipsilateral ICA after carotid intervention as a function of the degree of stenosis in the ipsilateral ICA. Both CAS (r 0.30) and CEA (r 0.33) demonstrate a positive correlation between the degree of stenosis and volume flow increase in the treated ICA. Fig 5 shows for all patients and control subjects the volume flow through the ipsilateral ICA, contralateral ICA, and BA, and the total cerebripetal volume flow (ICAs plus BA). Volume flow in the ipsilateral ICA in patients before CAS ( ml/min) or before CEA ( ml/min) was significantly decreased compared with control subjects ( ml/min; P.01). After CAS or CEA, no significant difference in volume flow in the ipsilateral ICA between patients and control subjects was found. No significant difference in volume flow in the contralateral ICA or BA was found between patients and control subjects. Furthermore, flow values in any of the arteries did not differ between patients who had CAS and patients undergoing CEA. The total volume flow in the cerebripetal arteries before carotid intervention in the CAS group ( ml/min) and CEA group ( ml/min) was significantly

3 JOURNAL OF VASCULAR SURGERY Volume 44, Number 1 van Laar et al 75 Fig 2. Selective angiograms of the right common carotid artery of a 52-year old woman before (a) and after (b) carotid angioplasty with stent placement (CAS) of the 90% stenosis in the right internal carotid artery (ICA). Quantitative magnetic resonance flow values before (c) and after (d) CAS are obtained by integrating across manually drawn regions that enclose the vessels. 1, Right ICA; 2, left ICA; 3, basilar artery. decreased compared with the control subjects ( ml/min; P.05) and increased significantly after carotid intervention (CAS group ml/min; CEA group ; P.05). No significant difference in total cerebripetal volume flow increase was found between CAS patients and CEA patients. DISCUSSION The study had two findings that were most important. First, in patients with symptomatic ICA stenosis, CAS results in a significant improvement in cerebral hemodynamics in a manner similar to that of CEA, as determined by MR volume flow measurements in the brain-feeding arteries. Second, total volume flow to the brain and volume flow in the stenosed ICA normalized after CAS compared with an age- and sex-matched control population. Technical advances in MR imaging have enabled noninvasive quantitative measurements of blood volume flow (ml/min) in the brain-feeding arteries. In this respect, MR volume flow has been used for the evaluation of cerebral hemodynamic impairment in patients with obstructive disease of the ICA or posterior circulation, 11,12 arteriovenous malformations, 8,13 and cerebral ischemia. 14,15 MR volume flow quantification has also been useful for the evaluation of vascular interventions 16 such as extracranial-intracranial bypass surgery, CEA, 6,17 and angioplasty of the vertebrobasilar arter - ies. 18 In addition, it was demonstrated that in patients with symptomatic vertebrobasilar disease, a management algorithm consisting of quantitative MR volume flow measurements could identify patients at high stroke risk 7 and guide the need for intervention. CAS has emerged as a potential alternative to CEA for the treatment of high-grade ICA stenosis, and several large randomized trials directly comparing CAS with CEA are currently underway. 4 In the present study, we demon - strated that the effects of CAS on cerebral hemodynamics are similar to those seen after CEA. A previous study only evaluating the effect of CAS in 12 patients with 70% stenosis of the ICA, demonstrated an increase in flow in the treated artery from 150 ml/min to 282 ml/min and little 19 change in other extracranial arteries. The main difference between the latter study and our study is that we also investigated the changes in blood flow before and after CEA. Furthermore, we showed normalization of the flow values compared with an age-

4 76 van Laar et al JOURNAL OF VASCULAR SURGERY July 2006 Volume flow (ml/min) Volume flow (ml/min) Before CAS Before CEA After CAS After CEA P<.001 P<.001 Fig 3. Quantitative changes in volume flow in the ipsilateral internal carotid arteries (ICAs) in patients with symptomatic ICA stenosis before and after carotid angioplasty with stent placement (CAS) (top) or carotid endarterectomy (CEA) (bottom). After CAS or CEA, the mean volume flow in the ipsilateral ICA significantly increased (P.001). and sex-matched control population. Changes seen in patients undergoing CEA are consistent with previous studies showing normalization of impaired cerebral hemodynamics after CEA, as assessed by volume flow measurements. 5,6,17 Using MR flow quantification, Vanninen et al demonstrated that ICA flow increased from 143 to 233 ml/min and total flow increased from 583 to 664 ml/min. 6 Similar to our results, no significant change in flow in the contralateral ICA and posterior circulation was found. However, in another study in patients with severe ICA stenosis, BA flow decreased significantly after CEA. 17 The pre- and postoperative measurements are also in agreement with the historical data of carotid flow measurements during CEA using square-wave electromagnetic flow probes: ICA flow was 133 ml/min before 5 CEA and 212 ml/min after. In our study, the total cerebral blood flow in patients before CAS (495 ml/min) and CEA (496 ml/min) was significantly decreased compared with control subjects (576 ml/min). This may indicate incomplete compensatory supply to the brain, but we stress that several known possible collateral pathways, such as the ophthalmic arteries and leptomeningeal collaterals, were not included in the MR assessment. Another theory is that recurrent small infarctions (transient ischemic attacks) may lead to relatively hypoperfused areas in the brain. These areas may have decreased metabolism, which in its turn may be responsible for the decreased hemispheric flow. 20 A limitation of the present study is the relatively small sample size. The number of patients might have been too small to demonstrate potential small differences in vol- difference in volume flow (ml/min) before and after carotid intervention stenosis (%) ipsilateral ICA CEA CAS CEA CAS Fig 4. Quantitative changes in volume flow in the ipsilateral internal carotid artery (ICA) in patients with symptomatic ICA stenosis after carotid angioplasty with stent placement (CAS) or carotid endarterectomy (CEA), as a function of the degree of the preintervention stenosis (%) in the ipsilateral ICA. Both CAS (r 0.30) and CEA (r 0.33) demonstrate a positive correlation between the degree of stenosis and volume flow increase in the treated ICA.

5 JOURNAL OF VASCULAR SURGERY Volume 44, Number 1 van Laar et al 77 Fig 5. Quantitative volume flow (mean SEM) through the cerebripetal arteries in patients with symptomatic internal carotid artery (ICA) stenosis before and after carotid angioplasty with stent placement (CAS) or carotid endarterectomy (CEA), as well as in control subjects. Significant differences in volume flow between patients and controls; *P.01; **P.05. ume flow changes between patients who had CAS and those undergoing CEA. The sample size was, however, large enough to demonstrate significant improvement and normalization of volume flow after CAS and CEA. In the present study, no volume flow measurements were performed in the anterior, middle, or posterior cerebral arteries. Still, MR volume flow measurements in these arteries have been shown to be useful for the evaluation of intracranial cerebral hemodynamics. 7,11 CONCLUSION CAS results in a return of impaired cerebral hemodynamics to the normal range in a manner similar to that of CEA. Although these results are encouraging, the true role of CAS in the management of ICA stenosis remains to be determined by large randomized trials that compare it with CEA. MR volume flow quantification is a noninvasive method of monitoring the hemodynamic effects of CAS and CEA in patients with ICA stenosis both immediately after the procedure and in long-term follow-up. This method may be useful for noninvasive quantification of possible neointimal hyperplasia or restenosis, which may not be similar in the CAS and CEA subgroups. AUTHOR CONTRIBUTIONS Conception and design: PJL, JG, JH Analysis and interpretation: PJL, JG, FLM, WPM, JH Data collection: PJL Writing the article: PJL, JG, JH Critical revision of the article: FLM, WPM Final approval of the article: PJL, JG, FLM, WPM, JH Statistical analysis: PJL, JG, JH Obtained funding: Not applicable Overall responsibility: PJL REFERENCES 1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325: European Carotid Surgery Trialists Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet 1991;337: Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol 1998;55: Brown MM, Hacke W. Carotid artery stenting: the need for randomised trials. Cerebrovasc Dis 2004;18: Boysen G, Ladergaard-Pedersen HJ, Valentin N, Engell HC. Cerebral blood flow and internal carotid artery flow during carotid surgery. Stroke 1970;1: Vanninen R, Koivisto K, Tulla H, Manninen H, Partanen K. Hemodynamic effects of carotid endarterectomy by magnetic resonance flow quantification. Stroke 1995;26: Amin-Hanjani S, Du X, Zhao M, Walsh K, Malisch TW, Charbel FT. Use of quantitative magnetic resonance angiography to stratify stroke risk in symptomatic vertebrobasilar disease. Stroke 2005;36: Marks MP, Pelc NJ, Ross MR, Enzmann DR. Determination of cerebral blood flow with a phase-contrast cine MR imaging technique: evaluation of normal subjects and patients with arteriovenous malformations. Radiology 1992;182: Bamford JM, Sandercock PAG, Warlow CP, Slattery J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1989;20: Fox AJ. How to measure carotid stenosis. Radiology 1993;186: Rutgers DR, Blankensteijn JD, Van der Grond J. Preoperative MRA flow quantification in CEA patients: flow differences between patients who develop cerebral ischemia and patients who do not develop cerebral ischemia during cross-clamping of the carotid artery. Stroke 2000; 31: Kato T, Indo T, Yoshida E, Iwasaki Y, Sone M, Sobue G. Contrastenhanced 2D cine phase MR angiography for measurement of basilar artery blood flow in posterior circulation ischemia. AJNR Am J Neuroradiol 2002;23: Wasserman BA, Lin W, Tarr RW, Haacke EM, Muller E. Cerebral arteriovenous malformations: flow quantitation by means of twodimensional cardiac-gated phase-contrast MR imaging. Radiology 1995;194:681-6.

6 78 van Laar et al JOURNAL OF VASCULAR SURGERY July Van den Boom R, Lesnik Oberstein SA, Spilt A, Behloul F, Ferrari MD, Haan J, et al. Cerebral hemodynamics and white matter hyperintensities in CADASIL. J Cereb Blood Flow Metab 2003;23: Ho SS, Chan YL, Yeung DK, Metreweli C. Blood flow volume quantification of cerebral ischemia: comparison of three noninvasive imaging techniques of carotid and vertebral arteries. AJNR Am J Neuroradiol 2002;178: Hendrikse J, van der Zwan A, Ramos LM, Tulleken CA, Van der Grond J. Hemodynamic compensation via an excimer laser-assisted, high-flow bypass before and after therapeutic occlusion of the internal carotid artery. Neurosurgery 2003;53: Blankensteijn JD, Van der Grond J, Mali WPTM, Eikelboom BC. Flow volume changes in the major cerebral arteries before and after carotid endarterectomy: an MR angiography study. Eur J Vasc Endovasc Surg 1997;14: Guppy KH, Charbel FT, Corsten LA, Zhao M, Debrun G. Hemodynamic evaluation of basilar and vertebral artery angioplasty. Neurosurgery 2002;51: Martin AJ, Saloner DA, Roberts TP, Roberts H, Weber OM, Dillon W, et al. Carotid stent delivery in an XMR suite: immediate assessment of the physiologic impact of extracranial revascularization. AJNR Am J Neuroradiol 2005;26: Van der Grond J, Eikelboom BC, Mali WPTM. Flow-related anaerobic metabolic changes in patients with severe stenosis of the internal carotid artery. Stroke 1996;27: Submitted Feb 6, 2006; accepted Mar 9, 2006.