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ACCF/SCAI/SVMB/SIR/ASTIN CLINICAL EXPERT CONSENSUS DOCUMENT

ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on Carotid Stenting

A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (ACCF/SCAI/SVMB/SIR/ASITN Clinical Expert Consensus Document Committee on Carotid Stenting)

American Society of Interventional & Therapeutic Neuroradiology Society for Cardiovascular Angiography and Interventions Society for Vascular Medicine and Biology Society of Interventional Radiology, Eric R. Bates, MD, FACC, Chair, Writing Committee Member, Joseph D. Babb, MD, FACC, FSCAI, Writing Committee Member, Donald E. Casey, Jr, MD, MPH, MBA, FACC, Writing Committee Member, Christopher U. Cates, MD, FACC, FSCAI, Writing Committee Member^_*, Gary R. Duckwiler, MD, FASITN, Writing Committee Member, Ted E. Feldman, MD, FACC, FSCAI, Writing Committee Member^_*, William A. Gray, MD, FACC, FSCAI, Writing Committee Member^_*, Kenneth Ouriel, MD, FACC, Writing Committee Member, Eric D. Peterson, MD, MPH, FACC, Writing Committee Member, Kenneth Rosenfield, MD, FACC, FSCAI, Writing Committee Member^_*,, John H. Rundback, MD, FSIR, Writing Committee Member, Robert D. Safian, MD, FACC, FSCAI, FSVMB, Writing Committee Member, Michael A. Sloan, MD, MS, FACC, Writing Committee Member, Christopher J. White, MD, FACC, FSVMB, FSCAI, Writing Committee Member, Robert A. Harrington, MD, FACC, Chair, Task Force Member, Jonathan Abrams, MD, FACC, Task Force Member^¶, Jeffrey L. Anderson, MD, FACC, Task Force Member, Eric R. Bates, MD, FACC, Task Force Member, Mark J. Eisenberg, MD, MPH, FACC, Task Force Member, Cindy L. Grines, MD, FACC, Task Force Member, Mark A. Hlatky, MD, FACC, Task Force Member, Robert C. Lichtenberg, MD, FACC, Task Force Member, Jonathan R. Lindner, MD, FACC, Task Force Member, Gerald M. Pohost, MD, FACC, Task Force Member, Richard S. Schofield, MD, FACC, Task Force Member, Samuel J. Shubrooks, JR, MD, FACC, Task Force Member, James H. Stein, MD, FACC, Task Force Member, Cynthia M. Tracy, MD, FACC, Task Force Member, Robert A. Vogel, MD, FACC, Task Force Member^||, Deborah J. Wesley, RN, BSN, Task Force Member

	Table of Contents

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

Executive Summary......128

Introduction......129

Background......129

Carotid Artery Disease......130

Neurovascular Anatomy and Physiology......130

Pathology and Pathophysiology......132

Natural History and Risk Stratification......132

Patient Evaluation......132

Clinical Evaluation......132

Noninvasive Testing......133

Carotid Duplex......133

Transcranial Doppler (TCD)......134

MRA......134

CTA......135

Choice of Noninvasive Diagnostic Test......135

Carotid Angiography......135

Medical Therapy......136

Risk Factor Modification......136

Hypertension Therapy......136

Smoking Cessation......136

Dyslipidemia Therapy......137

Diabetes......137

Obesity......137

Other Risk Factors......137

Pharmacological Therapy......137

Aspirin......137

Dipyridamole......137

Thienopyridines......138

Antiplatelet Treatment Failures......138

Warfarin......139

Lipid-Lowering Therapy......139

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)......139

CEA......139

Historical Perspective......139

Technique......139

Observational Studies......140

Randomized Clinical Trials......140

Indications......141

Contraindications......141

Complications......141

CAS......141

Historical Perspective......141

Technique......142

Carotid Access......142

Carotid Artery Angioplasty and Stenting......142

Embolic Protection......144

Types of EPDs......144

Advantages and Limitations of EPDs......145

Early CAS Experience......145

Contemporary Prospective Multicenter Registries......146

Early Randomized Clinical Trials......149

Contemporary Randomized Clinical Trials in High-Risk Patients......149

Randomized Clinical Trials in Progress......150

Other CAS Trial Designs......150

Nonatherosclerotic Disease......150

Indications......151

Contraindications......151

Complications of CAS......151

Clinical Decision Making......151

Medical Therapy Versus Revascularization......151

Revascularization in Symptomatic Patients......152

Revascularization in Asymptomatic Patients at Low Risk for CEA......152

Revascularization in Asymptomatic Patients at High Risk for CEA......153

Age......153

Women......153

Need for CABG in Patients With Carotid Stenosis......153

Preoperative Assessment Prior to Noncardiac Surgery......154

Atrial Fibrillation......154

Carotid Artery Dissection......154

Intracranial Disease......154

Management of the Carotid Stent Patient......154

Preprocedural Management......154

Intraprocedural Management......154

Antithrombotic Medications......154

Hemodynamic Monitoring and Support......154

Neurological Evaluation and Rescue......154

Postprocedural Management......155

Interventional Suite Training, Credentialing, and Regulatory Issues......156

Physician Training and Credentialing......156

Cognitive and Technical Training......156

Procedure Volume......156

Simulator-Based Training......159

Proctoring......159

Credentialing......159

Device-Specific Training......159

Facility Requirements......159

Interventional Suite......159

Interventional Equipment......160

Personnel......160

Quality Assessment Monitoring......160

National Data Registries......160

Reimbursement......161

Future Directions......161

Training and Proficiency......161

Quality Assessment and Improvement......161

New Devices......162

New Trials......162

New Indications......162

References......162

Appendix 1......168

	Preamble

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

The Task Force on CECDs makes every effort to avoid any actual or potential conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing panel. Specifically, all members of the writing panel are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest to inform the writing effort. These statements are reviewed by the parent task force, reported orally to all members of the writing panel at the first meeting, and updated as changes occur. The relationships with industry information for writing committee members and peer reviewers are published in the appendices of the document.

Robert A. Harrington, MD, FACC, Chair, ACCF Task Force on Clinical Expert, Consensus Documents

	Executive Summary (recommendations are highlighted in green text for easy identification)

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
Introduction.   Stroke is the third leading cause of death (164,000 deaths/year) in the U.S., behind heart disease and cancer. There are approximately 1 million stroke-related events each year, including 500,000 new strokes, 200,000 recurrent strokes, and 240,000 transient ischemic attacks (TIAs). Carotid occlusive disease amenable to revascularization accounts for 5% to 12% of new strokes.

Evaluation.   Patients with temporary retinal or hemispheric neurological deficits should be screened for extracranial carotid artery disease. In asymptomatic patients, there are no guidelines to support routine screening for carotid artery stenosis, except for some patients scheduled for coronary artery bypass graft surgery (CABG). Prior to CABG, carotid duplex screening is recommended in asymptomatic patients with age greater than 65 years, left main coronary stenosis, peripheral arterial disease, history of smoking, history of TIA or stroke, or carotid bruit. In other patients with asymptomatic carotid bruits, diagnostic tests for carotid disease should only be performed in those patients who are also considered good candidates for carotid revascularization.

Imaging.   Noninvasive imaging is useful to assess carotid stenosis severity and guide treatment. Carotid duplex is the most widely available and least expensive noninvasive imaging procedure. When carotid duplex results are unclear, diagnostic accuracy may increase to greater than 90% when it is used in conjunction with computed tomographic angiography and/or magnetic resonance angiography. Vascular laboratories must have strict quality assurance programs to establish optimal internal diagnostic criteria, employ credentialed vascular technologists, and obtain vascular laboratory accreditation. Recognition of normal and variant anatomy of the aortic arch and the cervicocerebral circulation is required for successful performance of carotid angiography and endovascular intervention. Selective angiography of both carotid arteries was recommended prior to CAS.

Medical Therapy.   Cardiovascular risk factor modification to target levels with medical therapy is recommended to limit progression of atherosclerosis and decrease clinical events, irrespective of carotid artery revascularization. Antiplatelet therapy is recommended for symptomatic patients. Either aspirin (81 to 325 mg), extended-release dipyridamole plus aspirin, or clopidogrel can be used. Medical therapy alone is preferred for patients in whom the risk of revascularization outweighs its benefits, including patients who are at low risk for stroke with medical therapy (symptomatic stenosis less than 50%, asymptomatic stenosis less than 60%), and those with a high risk of procedure-related stroke or death due to clinical or technical factors.

Carotid Endarterectomy (CEA).   Current AHA guidelines recommend CEA in symptomatic patients with stenosis 50% to 99%, if the risk of perioperative stroke or death is less than 6%. For asymptomatic patients, AHA guidelines recommend CEA for stenosis 60% to 99%, if the risk of perioperative stroke or death is less than 3%. The 2005 guidelines from the American Academy of Neurology recommend that eligible patients should be 40 to 75 years old and have a life expectancy of at least 5 years.

Carotid Stenting.   Carotid artery stenting is a reasonable alternative to CEA, particularly in patients at high risk for CEA. Although there are no randomized studies comparing CAS with and without embolic protection devices (EPDs), the use of EPDs appears to be important in reducing the risk of stroke during CAS. Careful neurological assessment is required before and after CAS. The Centers for Medicare & Medicaid Services (CMS) reimbursement is limited to qualified institutions and physicians when using Food and Drug Administration (FDA)-approved stents and EPDs for high-risk patients with symptomatic stenosis greater than 70%, and for high-risk patients (symptomatic stenosis greater than 50%, asymptomatic stenosis greater than 80%) enrolled in a Category B Investigational Device Exemption (IDE) trial or post-approval study. At the present time, there is insufficient evidence to support CAS in high-risk patients with asymptomatic stenosis less than 80% or in any patient without high-risk features. The results of ongoing randomized trials will define the future role of CAS in low-risk patients. Further study is needed in asymptomatic high-risk patients to determine the relative merits of CAS compared with best medical therapy.

Training and Credentialing.   Operators should previously have achieved a high level of proficiency in catheter-based intervention, complete dedicated training in CAS, and be credentialed at their hospital. Detailed clinical documents on training and credentialing for CAS have been published by 2 multispecialty consensus groups. The elements for competency include requirements for cognitive, technical, and clinical skills, including cervicocerebral angiography and CAS. Hospitals are required to maintain independent oversight of CAS outcomes by a hospital-based oversight committee. The CMS has created facility credentialing requirements for CAS reimbursement. Individual operators and institutions are required by CMS to track their outcomes and to make their data available for submission to a national database.

	Introduction

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
The Writing Committee consisted of acknowledged experts in the field of carotid artery disease. In addition to members of ACCF, the Writing Committee included representatives from the SCAI, SVMB, SIR, ASITN, and Society for Vascular Surgery (SVS). Representation by an outside organization does not necessarily imply endorsement. The document was reviewed by 4 official representatives from by the ACCF and SCAI and 12 organizational reviewers from the SVMB, SIR, ASITN, and SVS, as well as 6 content reviewers. This document was approved for publication by the governing bodies of ACCF in September 2006. In addition, the governing boards of the SCAI, SVMB, SIR, and ASITN reviewed and formally endorsed this document. This document will be considered current until the Task Force on CECDs revises or withdraws it from publication or a guideline relevant to the topic is published.

	Background

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
Stroke is the third leading cause of death (164,000 deaths/year) in the U.S., behind heart disease and cancer (1). There are approximately 1 million stroke-related events each year, including 500,000 new strokes, 200,000 recurrent strokes, and 240,000 TIAs (1,2). On average, someone has a stroke every 45 s and someone dies of stroke every 3 min. Stroke is the leading cause of serious long-term disability, causing functional limitations in more than 1.1 million Americans. The risk of stroke increases with each decade of life, and the growth in the elderly population will be a source of increasing disability due to stroke. African Americans, Hispanics, and diabetics are at increased risk for stroke mostly due to their strong association with hypertension (3). In 2006, the direct and indirect cost of stroke is estimated at $57.9 billion (1).

Atherosclerosis accounts for up to one-third of all strokes. Approximately 50% of strokes occur in the distribution of the carotid arteries, and while extracranial carotid disease is more frequent in Caucasians, intracranial disease is more frequent in African Americans, Hispanics, and Asians (4–7). Carotid occlusive disease amenable to revascularization accounts for 5% to 12% of new strokes (8–11). The pattern of progression of carotid stenosis is unpredictable, and disease may progress swiftly or slowly, or remain stable for many years. Nearly 80% of strokes due to embolization in the carotid distribution may occur without warning, emphasizing the need for careful patient follow-up (8–10).

Current annual carotid revascularization volumes include 117,000 CEA (1) and 7,000 to 10,000 CAS procedures. The first devices for CAS in high-risk patients were approved by the FDA in August 2004, and limited reimbursement for CAS was approved by the CMS in March 2005. Carotid artery stenting is less invasive than CEA, and the number of CAS procedures may increase rapidly, depending on the outcomes of ongoing registries and randomized clinical trials, and on CMS reimbursement. The purpose of this document is to summarize what is currently known about CAS and to lay the foundation for the development of interdisciplinary guidelines.

	Carotid Artery Disease

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
Neurovascular Anatomy and Physiology.   Recognition of normal and variant anatomy of the aortic arch and the cervicocerebral circulation is required for successful performance of carotid angiography and endovascular intervention (12). It is important to recognize the type of aortic arch and the configuration of the great vessels, since these anatomic features influence procedure complexity. There are 3 types of aortic arch that are based on the relationship of the innominate artery to the aortic arch (Fig. 1) (13). The Type I aortic arch is characterized by origin of all 3 great vessels in the same horizontal plane as the outer curvature of the aortic arch. In the Type II aortic arch, the innominate artery originates between the horizontal planes of the outer and inner curvatures of the aortic arch. In the Type III aortic arch, the innominate artery originates below the horizontal plane of the inner curvature of the aortic arch. The more inferior the origin of the target artery (i.e., Type II or III aortic arch), the greater the difficulty in gaining access to the carotid artery.

View larger version (14K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Aortic Arch Types Reprinted with permission from Casserly IP, Yadav JS. Carotid intervention. In: IP Casserly, R Sachar, JS Yadav, editors. Manual of peripheral vascular intervention. Philadelphia, PA: Lippincott Williams & Wilkins, 2005:83–109 (13).

View larger version (158K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Great Vessel Anatomy CCA = common carotid artery; SubA = subclavian artery; VA = vertebral artery. Reprinted with permission from Cho L, Mukherjee D. Basic cerebral anatomy for the carotid interventionalist: the intracranial and extracranial vessels. Catheter Cardiovasc Interv 2006;68:104–11. Copyright © 2006 John Wiley & Sons (15a).

View larger version (31K): [in this window] [in a new window] [Download PPT slide]   Figure 3 Extracranial and Intracranial Circulation Reprinted with permission from White CJ, Ramee SR, Bendick PJ, Safian RD. Peripheral Vascular Intervention: The Manual of Interventional Cardiology. 3rd edition. Royal Oak, MI: Physicians’ Press, 2001:831–901 (15b). ACA = anterior communicating artery; BA = basilar artery; LACA = left anterior cerebral artery; LCCA = left common carotid artery; LECA = left external carotid artery; LICA = left internal carotid artery; LMCA = left middle cerebral artery; LPCA = left posterior cerebral artery; LSA = left subclavian artery; LVA = left vertebral artery; RACA = right anterior cerebral artery; RCCA = right common carotid artery; RECA = right external carotid artery; RICA = right internal carotid artery; RMCA = right middle cerebral artery; RPCA = right posterior cerebral artery; RSA = right subclavian artery; RVA = right vertebral artery.

Recognition of normal vascular physiology is necessary for understanding possible cardiovascular responses to carotid intervention. Compression or stretching of the carotid sinus can cause a vasovagal (hypotension and bradycardia) or vasodepressor (hypotension without bradycardia) response and systemic hypotension. These responses are mediated via stimulation of the carotid sinus nerve (a branch of the glossopharyngeal nerve) in the carotid baroreceptor, and vagus nerve activation leading to inhibition of sympathetic tone. The sensitivity of the carotid baroreceptors is variable and may be affected by medications (e.g., vasodilators and beta-blockers might increase sensitivity), the presence of calcified plaque in the carotid bulb (increased sensitivity), or prior CEA (decreased sensitivity).

Pathology and Pathophysiology.   Although atherosclerosis is the most common disease of the carotid circulation, it is important to be aware of other conditions that may be associated with cerebral ischemia and infarction. These conditions include diseases of the aorta (dissection, aneurysm, aortitis), arteritis, fibromuscular dysplasia, dissection, dolichoectasia, primary vascular tumors, trauma, and complications of head and neck cancer.

Atherosclerosis is a systemic disease, and the pathophysiology of carotid atherosclerosis is similar to that in other vascular beds. However, atherosclerosis in the carotid artery is usually unifocal, and 90% of lesions are located within 2 cm of the ICA origin (15). The degree of carotid stenosis is associated with stroke risk. Carotid atherosclerosis can produce retinal and cerebral symptoms by 1 of 2 major mechanisms, including progressive carotid stenosis leading to in-situ occlusion and hypoperfusion (less common), or intracranial arterial occlusion resulting from embolization (more common). Patients with and without carotid stenosis may develop symptomatic cerebral hypoperfusion from systemic causes. Patients presenting with carotid distribution cerebral ischemia should be thoroughly evaluated for treatable causes, including sources of emboli from the carotid arteries, heart, and aortic arch.

Natural History and Risk Stratification.   Patients with asymptomatic carotid bruits are more common than patients with symptomatic carotid stenosis. A carotid bruit is identified in 4% to 5% of patients age 45 to 80 years, and should be heard in the majority of patients with carotid stenosis greater than or equal to 75% (15). Carotid stenoses greater than or equal to 50% have been identified in 7% of men and 5% of women older than 65 years (16). However, a bruit may be absent if there is slow flow through a severe stenosis, so cervical bruits are neither specific nor sensitive for identifying severe carotid stenosis. The risk of progression of carotid stenosis is 9.3% per year; risk factors for progression include ipsilateral or contralateral ICA stenosis greater than 50%, ipsilateral ECA stenosis greater than 50%, and systolic blood pressure greater than 160 mm Hg (17).

The annual stroke risk in patients with carotid stenosis is most dependent on symptom status and stenosis severity, but is also influenced by the presence of silent cerebral infarction, contralateral disease, extent of collaterals, the presence of atherosclerotic risk factors, plaque morphology, and other clinical features. The stroke risk is much higher in symptomatic patients than in asymptomatic patients, and the risk is highest immediately after the initial ischemic event. In the NASCET (North American Symptomatic Carotid Endarterectomy Trial) (18,19), the risk of stroke in the first year was 11% for carotid stenosis 70% to 79% and 35% for carotid stenosis greater than or equal to 90%. Patients with carotid stenosis 70% to 99% had a 2-year ipsilateral stroke risk of 26%. Interestingly, patients with near-occlusion have a lower stroke risk, ranging from 8% at 5 years (20) to 11% at 1 year (21). The annual ipsilateral stroke rate drops to about 3% within 2 to 3 years.

In asymptomatic patients, the annual stroke risk is much lower than in symptomatic patients, and is less than 1% for carotid stenoses less than 60% and 1% to 2.4% for carotid stenoses greater than 60% (22,23). In the ACST (Asymptomatic Carotid Surgery Trial), there was no relationship between the risk of stroke and increasing stenosis severity from 60% to 99% (23). Patients referred for CABG have a particularly high incidence of asymptomatic carotid stenosis with a prevalence of 17% to 22% for carotid stenosis greater than 50% and 6% to 12% for carotid stenosis greater than 80%. The risk of perioperative stroke after CABG is 2% for carotid stenosis less than 50%, 10% for carotid stenosis 50% to 80%, and as high as 19% for carotid stenosis greater than 80% (24).

Other factors that influence the risk of stroke include the clinical manifestations of TIA, prior silent stroke, contralateral disease, intracranial disease, intracranial collaterals, and plaque morphology. In the NASCET study, the 3-year risk of ipsilateral stroke was 10% after retinal TIAs and 20.3% after hemispheric TIAs (25). The presence of concomitant intracranial disease raised the 3-year risk of stroke from 25% to 46% in patients with carotid stenosis 85% to 99% (26). The prevalence of silent cerebral infarction in patients with asymptomatic carotid stenosis is estimated to be 15% to 20% (22), and appears to be associated with a higher risk of subsequent stroke. In patients with ICA occlusion, the annual stroke risk is influenced by the number of intracranial collateral pathways (27). In NASCET patients with carotid stenosis 70% to 99%, the presence of contralateral carotid occlusion increased stroke risk by more than 2-fold (28), whereas the presence of collaterals decreased the stroke risk by more than 2-fold (29). Stroke risk in symptomatic patients may also be influenced by plaque morphology, including the presence of hypoechoic or echolucent plaque (30,31) and plaque ulceration (32,33) irrespective of the degree of stenosis.

	Patient Evaluation

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
Clinical Evaluation.   Clinical syndromes associated with extracranial carotid occlusive disease are summarized in Table 2. Transient ischemic attacks are medical emergencies, characterized by temporary focal retinal and/or hemispheric neurological deficits that resolve within 24 h. In one study (34), 11% of patients developed a stroke within 90 days after TIA, one-half occurring within the first 2 days. Patients with both retinal and hemispheric symptoms usually have severe extracranial carotid disease. Rarely, patients with bilateral high-grade ICA stenosis or occlusion may have transient bilateral hemispheric symptoms, which may be mistaken for vertebrobasilar insufficiency.

A complete neurological assessment includes the cardiovascular examination (auscultation of the neck for carotid bruits and transmitted murmurs), fundoscopic examination (to detect retinal embolization), and a focused neurologic examination (to correlate neurological symptoms with an ischemic territory). For example, aphasia usually localizes to the left hemisphere, irrespective of the patient’s handedness, and hemispatial neglect in the setting of left motor, sensory, or visual signs indicates a right hemisphere lesion. The National Institutes of Health Stroke Scale (NIHSS) (35) is used to quantify the neurological deficit and predict outcome after ischemic stroke (36). Clinical findings must be correlated with brain and vascular imaging to determine whether or not a carotid stenosis is symptomatic.

Imaging is critical to assess the anatomy and structural pathology of the brain (e.g., mass, old or new stroke, hemorrhage, atrophy, or other confounding disease state) and the carotid artery (e.g., anatomic configuration, stenosis, plaque morphology, associated lesions, vasculitis, or dissection), and guide treatment. In asymptomatic patients, there are no guidelines to support routine screening for carotid artery stenosis, except for some patients scheduled for CABG. Prior to CABG, carotid duplex screening is recommended in asymptomatic patients with age greater than 65 years, left main coronary stenosis, peripheral arterial disease, history of smoking, history of TIA or stroke, or carotid bruit (24). In other patients with asymptomatic carotid bruits, diagnostic tests for carotid disease should only be performed in those patients who are also considered good candidates for carotid revascularization.

Noninvasive Testing.   Carotid duplex, magnetic resonance angiography (MRA), and computed tomographic angiography (CTA) are often recommended for the initial evaluation of most patients with carotid artery disease, allowing assessment of lesion characteristics (i.e., ulceration, composition) and stenosis severity. The NASCET (18,19) and the ECST (European Carotid Surgery Trial) (37,38) studies showed benefit for CEA in patients with symptomatic carotid stenosis greater than 50%, and the ACAS (Asymptomatic Carotid Atherosclerotic Study) (22) and ACST (23) trials showed benefit for CEA in asymptomatic patients with carotid stenosis greater than 60%. Although the NASCET, ECST, and ACAS studies utilized angiographic criteria for stenosis severity, noninvasive studies are usually performed in place of angiography, to assess stenosis severity and guide decisions about revascularization. Small differences in stenosis severity may impact decisions about revascularization by as much as 20% (39).

Carotid Duplex.   Carotid duplex utilizes spectral Doppler, color-flow, and B-mode (gray-scale) to evaluate the cervical carotid arteries from their supraclavicular origin to their retromandibular entrance into the skull base. The mainstay of carotid duplex evaluation is the determination of flow velocity using spectral Doppler analysis. Color-encoded and power Doppler imaging assist in assessment of stenosis severity in individuals with carotid tortuosity, where angle-corrected velocities can be unattainable (40), and may allow detection of residual flow in patients with subtotal occlusions or vascular calcification (41). B-mode imaging is used to identify sites for more focused Doppler evaluation, to directly evaluate cross-sectional narrowing, and to provide information regarding plaque morphology predictive of stroke risk, including surface irregularity (42), ulceration (33), and echolucency (30,43,44). B-mode may also be useful in measuring intima-media thickness, a possible marker of systemic atherosclerotic burden and cardiovascular risk used predominantly in trials assessing primary risk intervention strategies (45,46).

Diagnostic criteria for carotid duplex rely on peak systolic and end-diastolic velocities in the ICA and CCA, spectral patterns, and ICA/CCA velocity ratios. Unlike the linear measurements of diameter stenosis obtained with angiography, spectral velocities illustrate the effects of cross-sectional luminal narrowing. There are numerous diagnostic criteria for grading stenosis severity. Meta-analyses (39,47) and a multidisciplinary consensus conference (48) suggest that peak systolic velocity is the single most accurate duplex parameter for determination of stenosis severity. Compared with angiography, carotid duplex has a sensitivity of 77% to 98% and a specificity of 53% to 82% to identify or exclude an ICA stenosis greater than or equal to 70% (39). Women have higher flow velocities than men (49), which may affect decisions about revascularization.

In patients with a severe carotid stenosis or occlusion, compensatory increases in contralateral blood flow may result in spuriously high velocities in the contralateral ICA. In this situation, the ICA/CCA velocity ratio (ratio of peak systolic flow velocities in the proximal ICA and the distal CCA) is a better determinant of stenosis severity (50–52). Compensatory increased flow is also favored when color-flow or power Doppler show no evidence of a flow-limiting stenosis.

The accuracy of diagnostic criteria may vary between laboratories (53–55), optimal diagnostic criteria may change over time (56), and there is significant intraobserver variability (39,53,57). Vascular laboratories must have strict quality assurance programs to establish optimal internal diagnostic criteria, employ credentialed vascular technologists, and obtain vascular laboratory accreditation (Intersocietal Commission for the Accreditation of Vascular Laboratories; American College of Radiology). It is likely that reimbursement for these studies will be limited to accredited laboratories in the future.

It may be difficult to differentiate slow-velocity "trickle flow" (58) from complete occlusion, so power Doppler imaging or intravenous ultrasound contrast agents may be useful (59–61). Cardiac arrhythmias, arterial kinking, extensive calcification, high bifurcation, or unusual diseases (such as fibromuscular dysplasia or dissection) may make image interpretation more difficult. Lesions in the intracranial ICA and aortic arch cannot be imaged, although these occur infrequently (2% to 5% of cases) and rarely affect surgical decisions (58,62). Overall, despite these limitations, there is very high concordance between high quality carotid duplex and angiography; in some studies, the findings on subsequent angiography altered the revascularization decision in only 1% to 6% of cases (62–64). When carotid duplex results are unclear, diagnostic accuracy may increase to greater than 90% when it is used in conjunction with CTA and/or MRA (65).

Transcranial Doppler (TCD).   TCD, with or without color-coding, measures intracranial blood flow patterns, and indirectly assesses the effects of stenoses proximal or distal to the sites of insonation. It is particularly useful for assessment of intracranial stenosis (66). TCD alone is rarely useful for recognition of cervical carotid stenosis, but when used as an adjunct to carotid duplex, sensitivity is nearly 90% (67).

The clinical role for TCD in determining the appropriateness of carotid revascularization remains to be determined. However, several studies suggest that impaired cerebrovascular reserve by TCD, manifested by impaired cerebral blood flow augmentation in response to breath-holding or CO ₂ inhalation, may predict a 3-fold higher risk of subsequent neurological events in asymptomatic patients with extracranial carotid stenosis. In such patients, successful revascularization results in normalization of vasomotor reserve (68). Another study showed that absence of embolic signals in patients with asymptomatic carotid stenosis predicts a stroke rate of 1% per year (69).

MRA.   Perhaps more than any other imaging modality, MRA has benefited from dramatic technology advancements that have improved image quality. MRA allows imaging of intrathoracic and intracranial lesions not accessible by carotid duplex, although image quality is degraded by breathing artifact and venous contamination (70). Newer reconstruction algorithms (70,71), as well as the universal availability of MRA contrast agents, have increased imaging speed and enhanced MRA imaging consistency. When compared with conventional angiography, first-pass contrast enhanced three-dimensional MRA maximum intensity projections correlate with digital subtraction angiography stenosis in 90% of cases, and correlation is best for severe stenoses (72). Interpretability is enhanced by evaluating axial, sagittal, and coronal projections (73) and with 3-T magnets.

Advantages of MRA include avoidance of nephrotoxic contrast and ionizing radiation. Limitations include the inability to perform MRA due to claustrophobia, pacemakers, implantable defibrillators, and obesity; misdiagnosis of subtotal stenoses as total occlusions; or overestimation of carotid stenoses secondary to movement artifact. These errors may be lessened by short acquisition sequences, contrast enhancement (74), and by combining MRA and duplex data (75). The combination of these 2 tests provides better concordance with digital subtraction angiography than either test alone (combined 96% sensitivity and 80% specificity), but is not cost-effective for routine use (76).

MRA techniques may allow plaque characterization, including fibrous cap thickness and disruption, and intraplaque lipid content and hemorrhage (77,78). MRA has been used experimentally to predict flow profiles and wall stress dynamics affecting image quality and plaque stability (79). MRA evaluation of carotid arteries after stent placement has been performed, although artifacts due to magnetic susceptibility or Faraday shielding may lead to misdiagnosis (80).

CTA.   CTA allows orthogonal carotid imaging and simultaneous intracranial evaluation, but requires ionizing radiation and potentially nephrotoxic iodinated contrast. Like MRA, CTA is useful when carotid duplex is ambiguous, permitting visualization of aortic arch or high bifurcation pathology, reliable differentiation of total and subtotal occlusion, assessment of ostial and tandem stenoses, and evaluation of carotid disease in patients with arrhythmias, valvular heart disease, or cardiomyopathy. Since CTA relies on the recognition of contrast filling of the stenotic vessel lumen, it is less prone to overestimate stenosis severity due to turbulence and arterial tortuosity. Although CTA is extremely sensitive to the presence of calcification, it is less reliable than carotid duplex or MRA for assessing plaque vulnerability (81). When compared with carotid duplex, CTA is more specific for high-grade lesions, and in 1 study altered surgical planning in 11% of cases (82). When compared with enhanced MRA, 1 study showed that CTA was less reliable (70). With CTA, the sensitivity and specificity for detecting carotid stenosis greater than 70% was 85% to 95% and 93% to 98%, respectively (83,84). CTA sensitivity and accuracy can be increased by examining axial source images (83) and volume rendered projections (85), and by use of faster high resolution multislice scanners (86).

Choice of Noninvasive Diagnostic Test.   Carotid duplex is the most widely available and least expensive noninvasive imaging procedure. Whereas the advantages and limitations of each imaging procedure are previously described, we recommend that physicians learn about the tests available in their own institutions, and choose the best imaging modality.

Carotid Angiography.   Catheter-based arch and cerebral artery angiography is the reference standard for the evaluation of carotid artery disease. Single-plane angiography may underestimate the tortuosity of the great vessels, so orthogonal views, biplane angiography, or rotational acquisition is preferred. The purpose of angiography is to define the aortic arch type, the configuration of the great vessels, the presence of tortuosity and atherosclerotic disease in the arch and great vessels, and the condition of the intracranial circulation, particularly with respect to intracranial stenosis, aneurysm, arteriovenous malformations, and patterns of collateral blood flow. Such information will influence choice of catheters and the interventional strategy.

There are 3 methods for assessment of carotid stenosis severity, and each relies on different reference segments, resulting in different estimates of stenosis severity (87,88) (Fig. 4). By convention, the NASCET method has been adopted, utilizing the diameter of the proximal ICA above the carotid bulb as the reference diameter. Although decisions about the need for CEA are often made based on noninvasive imaging without carotid arteriography, all patients being considered for CAS must undergo angiography. In these patients, the NASCET definition for stenosis severity must be used, irrespective of estimates of stenosis severity by noninvasive methods.

View larger version (26K): [in this window] [in a new window] [Download PPT slide]   Figure 4 Angiographic Methods for Determining Carotid Stenosis Severity Reprinted with permission from Osborn AG. Diagnostic Cerebral Angiography. 2nd edition. Philadelphia, PA: Williams & Wilkins, 1999 (12). CC = common carotid; ECST = European Carotid Surgery Trial; NASCET = North American Symptomatic Carotid Endarterectomy Trial.

As an invasive procedure, cervicocerebral angiography shares the same potential complications with other angiographic techniques, including access site injury, blood transfusion, contrast nephropathy, anaphylactoid reactions, and atheroembolism. In patients with symptomatic cerebral atherosclerosis undergoing diagnostic cerebral angiography, the risk of stroke is 0.5% to 5.7%, and the risk of TIA is 0.6% to 6.8% (89). In asymptomatic patients in the ACAS trial, stroke occurred in 1.2% of patients after angiography (22). More recent studies reported neurological complication rates in less than 1% of patients, suggesting that the risk may be lower than previously reported (90,91). Possible explanations for these differences are improvements in equipment, technique, and operator experience; monitoring of catheter-tip pressure during angiography; and use of procedural heparin and antiplatelet agents.

	Medical Therapy

Top Table of Contents Preamble Executive Summary... Introduction Background Carotid Artery Disease Patient Evaluation Medical Therapy CEA CAS Clinical Decision Making Management of the Carotid... Interventional Suite Training,... Future Directions Staff Appendix References

 
Risk Factor Modification.   Identification of risk factors for stroke is important for stroke prevention, since modification of many of these risk factors can reduce the risk of stroke. Ethnicity, age, and family history are important determinants of stroke risk, but these cannot be modified. Although not specifically evaluated in patients with severe carotid artery stenosis, cardiovascular risk factor modification and medical therapy are recommended to limit progression of atherosclerosis and decrease clinical events, irrespective of carotid artery revascularization. Treatment goals are listed in Table 3 (92,93).

Smoking Cessation.   Smoking nearly doubles the risk of ischemic and hemorrhagic stroke (particularly subarachnoid hemorrhage), and the risk is directly proportional to the number of cigarettes smoked (99,100). The risk is even higher in female smokers who use oral contraceptives. Passive exposure to cigarette smoke nearly doubles the risk of stroke in spouses of smokers compared with their nonsmoking neighbors (101). The risk of stroke decreases to that of nonsmokers within 5 years after smoking cessation (102). Enrollment in a formal smoking cessation program, which includes nicotine replacement, bupropion, social support, and skills training, has proven to be the most effective approach for smoking cessation.

Dyslipidemia Therapy.   Although the epidemiological relationship between dyslipidemia and coronary artery disease is incontrovertible, its relationship with stroke is less well established. In fact, there is an inconsistent relationship between blood lipids and stroke. This is partly a result of combining ischemic and nonischemic stroke in the clinical reports. However, there is a strong relationship between total cholesterol, low-density lipoprotein cholesterol, and the extent of extracranial carotid artery atherosclerosis and wall thickness (103). A summary of over 70,000 patients at high risk for or with established coronary artery disease described a 21% relative risk reduction and a 0.9% absolute risk reduction for stroke within 5 years of treatment (104). These observations suggest a potential beneficial effect of lipid-lowering treatment on plaque stabilization, endothelial function, and inflammation in patients with cerebrovascular disease.

Diabetes.   Although diabetes is strongly associated with hypertension and hyperlipidemia, it is a potent independent risk factor for stroke, increasing the risk 2-fold compared with nondiabetics (105). The combination of diabetes and hypertension increases the risk of stroke 6-fold higher than in normal patients, and 2-fold higher than normotensive diabetics. Although tight glycemic control is unequivocally useful for prevention of microvascular complications (nephropathy, neuropathy, retinopathy) (106), the benefit for stroke reduction is less certain.

Obesity.   Abdominal obesity contributes more than body mass index to the presence of insulin resistance, hypertension, dyslipidemia, and the risk for stroke (107,108). There are no reports demonstrating reduction in stroke risk with weight loss, although diet and exercise are prudent because of their beneficial impact on hypertension, hyperlipidemia, and insulin resistance.

Other Risk Factors.   Elevated fibrinogen, C-reactive protein, and blood homocysteine levels are each independently associated with increased risk of cardiovascular disease and stroke, although dietary supplementation with vitamin B or folic acid does not alter this risk (109–111). There is an increased risk of stroke in women using oral contraceptives, although most of the risk appears to be concentrated in smokers and women older than 35 years of age; women under the age of 35 appear to have a low risk if other risk factors are absent (112). A stroke risk profile can assess the risk of stroke based on age, systolic blood pressure, antihypertensive therapy, diabetes, cigarette smoking, and history of coronary artery disease, congestive heart failure, left ventricular hypertrophy, or atrial fibrillation, although other factors (ethnicity, severity of carotid stenosis, history of TIA or stroke) are not included in this profile (113).

Pharmacological Therapy.   All patients with carotid artery disease should be placed on medical therapy, including antiplatelet therapy and other medications to treat modifiable atherogenic risk factors. For asymptomatic patients with one or more risk factors for atherosclerosis, antiplatelet therapy is indicated for primary prevention of cardiovascular events. For symptomatic patients (recent TIA or minor CVA), the recommendations for antiplatelet therapy are based on large stroke prevention studies (114–126) that included patients with different stroke etiologies (Table 4).

Dipyridamole.   Dipyridamole is not recommended for primary prevention of cardiovascular disease or stroke. The role of dipyridamole for secondary prevention of stroke is supported by 2 trials. Extended-release dipyridamole alone and extended-release dipyridamole plus aspirin were superior to placebo, but extended-release dipyridamole alone was no different than aspirin alone in the second ESP II (European Stroke Prevention Study) (118). In the ESPRIT (European/Australian Stroke Prevention in Reversible Ischemia Trial), extended-release dipyridamole plus aspirin was superior to aspirin alone for the secondary prevention of MI, stroke, or vascular death (119). Extended-release dipyridamole plus aspirin is being tested against clopidogrel in the PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial.

Thienopyridines.   Ticlopidine and clopidogrel have not been evaluated in large studies for primary prevention of major cardiovascular outcomes. Ticlopidine was useful for secondary prevention after stroke in the CATS (Canadian-American Ticlopidine Study) trial, and resulted in a 23% reduction in cardiovascular events compared with placebo (120). The TASS (Ticlopidine Aspirin Stroke Study) studied patients after TIA or major stroke (121); ticlopidine caused significantly fewer cerebrovascular events and less bleeding, but neutropenia complicated therapy in 0.9% of patients.

Clopidogrel has largely replaced ticlopidine because of a superior safety profile and once daily dosing. For preventing stroke in secondary prevention trials, clopidogrel was similar to aspirin in the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trial (122). The combination of clopidogrel plus aspirin was similar to aspirin alone in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial (124). In the MATCH (Atherothrombosis with Clopidogrel in High-Risk Patients With Recent Transient Ischemic Attack or Ischemic Stroke) trial, the combination of aspirin plus clopidogrel increased the risk of systemic and intracerebral hemorrhage, but did not decrease the risk of stroke compared with clopidogrel alone (123). In summary, aspirin and clopidogrel appear to have similar efficacy for secondary prevention of stroke, but the combination may increase the risk of serious bleeding, and is not superior to either drug alone.

Antiplatelet Treatment Failures.   Recurrent events can occur despite therapy with antiplatelet agents. One treatment option is the addition of warfarin therapy. Another treatment option, given the issue of aspirin or clopidogrel nonresponders, is dual antiplatelet therapy with aspirin plus clopidogrel. In some cases, triple drug therapy with aspirin and clopidogrel, plus either aspirin/dipyridamole, cilostazol, or warfarin may be warranted. None of these options are based upon clinical trial evidence, and there may be a higher risk of bleeding.

Warfarin.   Unless contraindicated, warfarin is recommended for primary and secondary prevention of stroke in patients with atrial fibrillation. However, in patients with noncardioembolic stroke enrolled in the WARSS (Warfarin Aspirin Recurrent Stroke Study) trial, there were no differences between warfarin and aspirin in stroke, death, or major bleeding (125). Moreover, the WASID (Warfarin Aspirin Symptomatic Intracranial Disease) trial failed to show an advantage for warfarin compared with aspirin (126). Therefore, based upon extrapolation from these trials, antiplatelet therapy is favored over warfarin in patients with carotid artery disease who are not at risk for cardioembolic stroke (129).

Lipid-Lowering Therapy.   Gemfibrozil reduced stroke rates by 24% in the VA-HIT (Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial) study (130). Niacin reduced stroke by 22% compared with placebo in the Coronary Drug Project (131). Pravastatin, simvastatin, and atorvastatin are approved by the FDA for stroke prevention in patients with coronary artery disease (132–134) although the benefits may be mediated by anti-inflammatory, plaque stabilization, and neuroprotective effects, rather than cholesterol reduction per se. Statins may be effective for secondary prevention in patients undergoing CEA (135). The SPARCL (Stroke Prevention with Aggressive Reduction of Cholesterol Levels) trial studied atorvastatin 20 mg for secondary prevention of stroke in 4,731 patients without coronary artery disease and documented a 16% relative risk reduction for recurrent stroke (136,136a). The National Cholesterol Education Program (NCEP) guideline recommends statins in patients with prior TIA or stroke or carotid stenosis greater than 50% stenosis (137). The American Stroke Association (ASA) also recommends statins for patients with ischemic TIA or stroke (138).

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs).   In patients with hypertension, the reduction in stroke risk is directly related to the reduction in blood pressure, regardless of which antihypertensive agents are prescribed. However, recent trials of ACE inhibitors and ARBs suggest that these agents may have benefits for stroke reduction that extend beyond their antihypertensive effects. The HOPE (Heart Outcomes and Prevention Evaluation) trial studied 9,297 patients with high cardiovascular risk, including 1,013 patients with previous TIA or stroke (139). Patients were randomized to ramipril 10 mg daily or placebo, and ramipril was associated with a 32% reduction in stroke over 5 years. Although ramipril was associated with a significant antihypertensive effect (2 to 3 mm Hg decline in systolic and diastolic blood pressure) and less carotid intima-media thickening (140), these benefits were felt to be insufficient to explain the dramatic decline in stroke. The PROGRESS (Perindopril Protection Against Recurrent Stroke Study) trial also supported the benefits of blood pressure lowering with ACE inhibitors (141). In the LIFE (Losartan Intervention for Endpoint) trial (142), losartan and atenolol achieved similar degrees of blood pressure reduction, but losartan was associated with a 13% reduction in cardiovascular events and a 25% reduction in stroke. Besides blood pressure reduction, other potential benefits of ACE inhibitors and ARBs include inhibition of angiotensin II-mediated vasoconstriction and vascular smooth cell proliferation, improved endothelial function, and enhanced fibrinolysis.

	CEA

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