Chapter 32 Carotid Artery Stenting
On May 6th, 2011, the U.S. Food and Drug Administration (FDA) followed up on the January 2011 recommendation of the FDA Circulatory System Device Panel1 and approved the RX Acculink carotid stent (Abbott Vascular, Santa Clara, Calif.) for use in conjunction with Abbott’s embolic protection device (EPD), the Accunet filter. The expanded label as a result of the FDA’s approval was for treatment of extracranial carotid stenosis in symptomatic and asymptomatic patients who would otherwise be considered standard risk for surgical carotid endarterectomy (CEA). This was a landmark event because for the first time, carotid stenting, at least in the United States, qualified as a standard-of-care treatment and was no longer investigational or experimental for the majority of patients with carotid artery disease. (Earlier in , the FDA had approved carotid artery stenting [CAS] for high CEA risk patients). This chapter reviews historical aspects and development of CAS, discusses stenting technique in detail, and reviews clinical trial data that support current indications for this procedure.
Surgical treatment for carotid artery stenoses was introduced in the early 1950s.2 Although early observational data suggested benefit for surgery over medical therapy, large prospective randomized trials investigating the beneficial effect of CEA on stroke reduction were not initiated until the late 1980s and early 1990s. Landmark studies including the North American Symptomatic Carotid Endarterectomy Trial (NASCET),3–6 European Carotid Surgery Trial (ECST),7 Asymptomatic Carotid Atherosclerosis Study (ACAS),8 and Asymptomatic Carotid Surgery Trial (ACST)9 confirmed the benefits of surgery over best available medical treatment for reducing the risk of stroke in both symptomatic (NASCET, ECST) and asymptomatic patients (ACAS, ACST). Carotid endarterectomy surgery is comprehensively discussed in Chapter 33.
Patients included in these surgical studies were carefully selected; specifically, subjects who were considered high CEA risk were excluded from participation. Thus, octogenarians, patients with recurrent stenosis following prior ipsilateral endarterectomy, intracranial stenosis that was more severe than the surgically accessible lesion in the neck, unstable angina pectoris, recent myocardial infarction (MI), contralateral CEA, patients on long-term anticoagulation therapy, and surgically inaccessible lesions were all excluded from these trials.3,8
The mission to develop safer percutaneous endovascular solutions to treat arterial stenosis was pioneered by Dotter10 and Gruntzig and Hopff11 in the 1960s and 1970s. In 1977, Klaus Mathias, an interventional radiologist, described a catheter system that could be used for performing balloon angioplasty of cervical carotid stenosis,12 and this was followed by a few case reports of successful carotid angioplasty performed in the surgical suite.13,14 In 1984, Vitek and his neuroradiology colleagues from the University of Alabama at Birmingham (UAB)15 reported angioplasty of the innominate artery aided by balloon occlusion protection of the common carotid artery (CCA). This early report represents the first percutaneous intervention performed with the benefit of distal embolic protection. During the 1980s, clinical reports of carotid angioplasty were sporadic and limited to small single-center series of patients.16 Kachel et al. summarized the results of carotid angioplasty published in the literature through 1995 and noted that 503 of the 523 (96%) procedures were technically successful. There were no deaths, major strokes occurred in 2.1%, and minor complications were in the single digits (6.3%).17 In 1985, Rabkin and Germashev began using early-generation nitinol (an alloy of nickel and titanium) stents as an endovascular prosthesis and subsequently reported their 5-year experience.18
Resistance to widespread acceptance and the slow progress of angioplasty involving the supraaortic vessels was largely due to two major concerns: (1) local vessel injury related to balloon inflation causing a flow-limiting dissection with a risk of acute vessel closure (prestent era), and (2) the risk of distal embolization. In later years, these key limitations would be overcome by the introduction and widespread adoption of stents and EPDs.
In March 1994, Iyer, Vitek, and Roubin initiated the carotid angioplasty program at UAB under carefully scrutinized institutional protocols.19 Initial interventions were performed using stand-alone balloon angioplasty (no stents). To maximize the luminal result, a long inflation was performed using a 5-mm over-the-wire balloon; the center port of this balloon could accommodate a 0.035-inch guidewire. Once the balloon was in place, the wire was withdrawn, and oxygenated arterial blood withdrawn from the femoral artery was infused through the center port of the balloon with the help of a special pump device, permitting a long 10-minute balloon inflation. The first four patients were treated without complications. Patient #5, a woman with contralateral carotid occlusion, presented with a transient ischemic attack (TIA) related to a high-grade stenosis in the index carotid artery and underwent an uncomplicated balloon angioplasty procedure. Despite a perfectly acceptable angiographic result, approximately an hour after the procedure, there was acute closure of the angioplastied carotid artery. Although a technically successful, urgent reintervention with recanalization and stenting of the occluded vessel was performed, the patient did not recover from the major stroke related to the acute closure and subsequently expired. This case triggered the decision by the UAB group to perform elective carotid stenting—irrespective of the angiographic results of balloon angioplasty—and primary stenting became the intervention of choice for treatment of cervical carotid stenosis. The subsequent rapid adoption of this approach by interventional cardiologists in particular, and the endovascular interventional community in general, heralded the modern era of endovascular treatment for extracranial carotid bifurcation disease.19–22
Although balloon expandable stents were used in the first 100 patients, by the summer of 1995 (when the initial patients returned for their follow-up angiograms) it became clear that these stents were prone to deformation (stent crush) because of the superficial location of the carotid artery and the associated movements of the neck.23 The Alabama group were the first to report this complication, seen in approximately 15% of patients at 6-month follow-up.23 Fortunately, stent deformation was largely a cosmetic issue, with only one patient presenting with symptoms in this series. This observation, as well as the recognition that chances for regulatory approval for balloon expandable stents for treating extracranial carotid stenosis were slim, led to the rapid introduction, testing, and adoption of self-expanding stents. Stents have all but abolished acute carotid vessel closure, and in contemporary practice, primary carotid stenting is the norm. The reader should note that unlike in coronary arteries, the risk of acute stent thrombosis and instant restenosis, two major limitations of coronary stents, are nonissues when stents are deployed in the extracranial carotid location.
In 1996, Theron et al.24 reported results from his seminal work using his triple coaxial catheter that incorporated distal balloon occlusion for providing embolic protection during carotid bifurcation angioplasty. Unfortunately, this early-generation distal protection balloon could only be used with balloon angioplasty (and not with stents). By 2000, the first investigational distal balloon occlusion EPD, the Percusurge Guardwire (Medtronic, Minneapolis, Minn.) was introduced into clinical trials in the United States. This was soon followed by a number of clinical trials, all of which included a filter as the distal EPD. Unlike Theron’s distal occlusion balloon, the Percusurge balloon—as well as all such filters—can be used with both over-the-wire and monorail stent delivery systems. As increasing clinical data became available, use of distal protection devices was recognized and accepted by many (but not all25) as an integral if not mandatory part of carotid artery dilation and stenting.26–31 In our opinion, EPDs, when selected and used appropriately, improve procedure safety by significantly reducing the risk of procedure related embolic major and fatal strokes.
The multicenter Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS-I)9 was conducted between 1992 and 1997 in the United Kingdom during an era when stents were neither widely available nor perceived as integral. This prospective randomized trial compared outcomes of balloon angioplasty and CEA in 504 patients; only 55 patients (26%) within the group assigned to endovascular treatment received stents. Initially, stents were used only as a bailout treatment, with increased elective use toward the end of the study; distal protection devices were not used. Major event rates within 30 days after treatment did not differ significantly between endovascular treatment and surgery: disabling stroke or death (6.4% vs. 5.9%) and any major stroke lasting more than 7 days or death (10.0% vs. 9.9%). This study also demonstrated that endovascular techniques were superior to surgery when considering other risks related to the incision in the neck and use of general anesthesia. Cranial nerve injury was reported in 8.7% of surgical patients; no events occurred in patients undergoing endovascular procedures (P < 0.0001). Major groin or neck hematomas occurred less often after endovascular treatment than after surgery (1.2% vs. 6.7%, P < 0.0015). The results of this early clinical trial set the stage for investigation of carotid stenting.
The indications for carotid artery revascularization have been well delineated in the recent American Stroke Association/American College of Cardiology Foundation/American Heart Association (ASA/ACCF/AHA) et al. Guideline on the Management of Patients with Extracranial Carotid and Vertebral Artery Disease32 and essentially depend on symptomatic status and severity (degree) of stenosis. Hence, before an informed decision on a treatment option can be made (surgery or percutaneous intervention), it is critically important for patients and physicians to have a good understanding of the operator as well as the center’s procedural and 30-day experience and outcomes.
Symptomatic carotid stenosis refers to ischemia or infarction in the distribution of the internal carotid artery (ICA) causing neurological abnormalities that include but are not limited to contralateral motor and/or sensory events, speech, and/or visual problems (monocular blindness, field defects). Amaurosis fugax refers to transient monocular visual loss, typically described by the patient as a shade being drawn down or across the eye (amaurosis, Greek for “darkening,” and fugax, Latin for “fleeting”). Dizziness and problems with balance are symptoms that typically result from ischemia or infarction in the vertebrobasilar system, and the presence of a carotid artery stenosis in a patient presenting with dizziness is almost always incidental i.e., the carotid stenosis is most often asymptomatic and NOT causally related to the symptoms. The culprit stenosis is considered symptomatic for 6 months beyond the event. Additionally, the risk of recurrent stroke is lower in patients who present with amaurosis as the sole symptom in comparison to patients who present with a hemispheric TIA.
It is well accepted that revascularization should be offered to all symptomatic patients if the diameter of the ICA is reduced more than 70% as documented by noninvasive imaging, or more than 50% as documented by catheter angiography (Table 32-1). There is, however, one important caveat: the periprocedural risk of stroke or death related to the revascularization procedure (CEA or CAS) should be under 6%.32 In symptomatic patients, there is a well-established correlation between increasing stenosis severity and stroke risk. The NASCET study3 demonstrated the benefit of CEA over medical treatment for reducing the risk of future stroke in symptomatic patients with carotid stenosis between 70% and 99%. The NASCET results also showed that symptomatic patients with a lesser degree of stenosis (between 50% and 70%) benefit less. Revascularization is typically recommended in this group if there are additional unfavorable angiographic features (e.g., ulceration or other features associated with increased risk of vessel-to-vessel embolization).
|Indication Level||Symptomatic Stenosis*||Asymptomatic Stenosis*|
|Proven||70%-99% stenosis||>80% stenosis|
|Periprocedural complication risk <6%||Periprocedural complication risk <3%|
|Life expectancy >5 years|
|Acceptable||50%-69% stenosis||>60% stenosis|
|Periprocedural complication risk <3%||Periprocedural complication risk <3%|
|Unacceptable||<49% stenosis or||<60% stenosis or|
|Periprocedural complication risk >6%||Periprocedural complication risk >5%|
CABG, coronary artery bypass graft surgery.
* Lesion severity is determined according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology (i.e., the ratio between lumen diameter at the point of maximal stenosis and the lumen diameter of the non tapered segment of the distal internal carotid artery).153
Modified from Brott TG, Halperin JL, Abbara S, et al: ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery, developed in collaboration with the American Academy of Neurology and Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 57:1002–1044, 2011; and Roubin GS, Iyer S, Halkin A, et al. Realizing the potential of carotid artery stenting: proposed paradigms for patient selection and procedural technique. Circulation 113:2021–2030, 2006.
An important, albeit controversial and unsettled, issue in the treatment of symptomatic patients relates to the timing of the revascularization procedure after the index symptomatic event.33–37 Risk of a recurrent neurological event after a TIA or stroke is estimated to be between 15% and 20%, and this elevated risk persists for approximately 6 months after the initial event and underlies the rationale for the 6-month threshold for defining symptomatic patients. Proponents of early intervention i.e., within a few days of the symptomatic event. Argue that the highest risk of a recurrent event is during this early period and any delay in treatment will significantly diminish its therapeutic value, since a substantial portion of these patients would have already experienced a neurological event during the waiting period. A key reason underlying the reluctance of operators to perform revascularization (CEA or CAS) soon after a stroke (less so after a TIA) is the concern that early treatment increases the risk of hemorrhagic transformation of the culprit, (nonhemorrhagic) infarct. Although the increased risk of intracranial hemorrhage following early intervention has been challenged,33 a recent retrospective analysis38 of a large national inpatient database involving more than 57 million in-hospital admissions, conducted to determine the prevalence and risk factors of intracranial hemorrhage among patients undergoing CEA (N = 215,012) and CAS (N = 13,884), arrived at a different conclusion. Symptomatic presentations represented the minority of indications for CEA (n = 10,049 [5%]), as well as CAS (n = 1251 [10%]). Intracranial hemorrhage occurred significantly more frequently after CAS than CEA in both symptomatic (4.4% vs. 0.8%; P <0.0001) and asymptomatic presentations (0.5% vs. 0.06%; P <0.0001). Multivariate regression suggested that symptomatic presentations (vs. asymptomatic) and CAS procedures (vs. CEA) were both independently predictive of six- to sevenfold increases in the frequency of postoperative intracranial hemorrhage. The observations from this retrospective population-based analysis are at variance with observations from recent large prospective randomized trials involving symptomatic and asymptomatic patients, wherein the risk of mortality and major stroke was uniformly low in both CEA and CAS arms, and the higher incidence of neurological events in the CAS arm was a result of minor strokes (ischemic rather than hemorrhagic).39–41 Pending resolution of this issue by future studies, the current approach of waiting a minimum of 3 weeks following the index event (longer for larger strokes) is likely to continue.
Asymptomatic carotid disease refers to the presence of a stenosis resulting in a 60% or greater reduction of the luminal diameter of the extracranial ICA without symptoms of ipsilateral stroke, TIA, or amaurosis fugax. Treatment of patients with asymptomatic carotid artery stenosis has become extremely controversial, with two main issues fuelling this ongoing debate42–44:
1. Which asymptomatic patients (if any) are appropriate for intervention (CEA or CAS)? Current guidelines suggest that it is reasonable to refer asymptomatic patients for ICA revascularization in the setting of more than 80% stenosis and low periprocedural risk.32
Despite publication of several guidelines that provide a best assessment of current research, considerable divergence of opinion regarding care of the carotid artery remains an issue among physicians worldwide.45 One reason why enthusiasm for revascularization may be low is recognition that the annualized risk of a stroke in patients with asymptomatic carotid artery disease treated with contemporary medical treatment is low and dropping (Table 32-2). This reduction in stroke risk has been attributed to the benefits of risk-factor modification, use of antihypertensive medications,46 antiplatelet agents,47 smoking cessation, and statin therapy.48,49
The guidelines respond to this concern by limiting revascularization to those asymptomatic patients in whom periprocedural risk of a stroke or death is expected to be below 3%.32 Hence, some clinicians argue that there is an urgent need for a new three-arm randomized clinical trial for asymptomatic carotid disease that includes not only CEA and CAS but also has a medical treatment arm. A critical message from the asymptomatic CEA trials was that for surgical revascularization to be beneficial in reducing future stroke risk in asymptomatic patients (Table 32-3), the periprocedural risk of revascularization should not exceed 3%. If the risk breaches the 3% threshold, the difference in stroke risk between the medically treated arm and the surgical arm will not be significant (i.e., the benefit of stroke reduction from the surgery no longer accrues to the patient). The second Carotid Revascularization Endarterectomy versus Stenting Trial (CREST II) will be a three-arm study involving asymptomatic patients, and this protocol is currently under review for funding by the National Institutes of Health (NIH).
Much of the controversy surrounding treatment of asymptomatic carotid stenosis could be resolved if physicians had a method of reliably identifying the asymptomatic patient at high risk for a future stroke; interventional treatment could then be selectively directed at these patients. Understandably, such an approach would greatly improve the yield and cost-effectiveness of prophylactic invasive treatment with either CEA or CAS.50 Some of the metrics that have been proposed as predictors of increased risk of ipsilateral ischemic events in asymptomatic patients with carotid stenosis include higher grades of stenosis or substantial progression of carotid stenosis to a higher grade,51,52 unfavorable plaque characteristics and composition, including plaque ulceration and echolucency,53,54 or verifying the presence or absence of microemboli by using transcranial Doppler.55–58 Other clinical and radiological markers for predicting an increased risk of stroke in asymptomatic patients include occult cerebral infarction on brain imaging studies,59 contralateral carotid occlusion,60 or detection of intraplaque hemorrhage by magnetic resonance imaging (MRI).61 Nicolaides et al.62 have suggested that combining clinical risk factors, such as diabetes and smoking, with high-risk ultrasound features (e.g., echolucent plaque) may help identify the high-risk asymptomatic patient. These are listed in Table 32-4.
|High-grade carotid stenosis with substantial progression||Bock,51 Hirt52|
|Contralateral carotid occlusion||AbuRahma60|
|Plaque composition, ulceration, or echolucency||Nicolaides,53 Spence54|
|Intraplaque hemorrhage||Altaf 61|
|Plaque composition and clinical risk factors||Nicolaides62|
|Microembolization||Abbott,55 Markus,56 Spence57,58|
|Occult cerebral infarction||Norris59|
Although one cannot dispute the clinical appeal and practical usefulness of being able to identify the asymptomatic patient at high risk for a stroke, none of the approaches outlined thus far have been validated to justify and provide clinically relevant recommendations. Hence, at present, degree of carotid diameter stenosis severity remains the predominant basis for clinically deciding whether or not to treat patients with asymptomatic carotid stenosis.
In contemporary practice, most clinicians will (should) only treat an angiographically confirmed 80% or greater, unilateral, incidentally discovered (i.e., diagnosed on routine duplex screening, following workup of a carotid bruit) asymptomatic carotid stenosis. Patients with stenosis less than 60% are managed medically, with periodic (usually annual) ultrasound surveillance to monitor stenosis progression. Although stenosis severity between 60% and 80% is typically managed with conservative medical treatment, this recommendation may have to be altered based on individual circumstances. Some examples include:
In the absence of an established reliable method of identifying the asymptomatic patient with carotid stenosis at high risk for developing a future neurological event, the decision to treat is predominantly based on degree of stenosis, an approach supported by the large CEA clinical trials. The threshold for treating asymptomatic carotid stenosis is 80% or greater stenosis confirmed by angiography (NASCET criteria), with corresponding elevated duplex velocities. Although standard risk-factor modification approaches should be implemented in all these patients, there is no convincing evidence to date that risk-modifying measures by themselves will reduce stroke risk in patients with severe degrees of stenosis that cannot be further improved with revascularization when the periprocedural risk is 3% or less. This nonnegotiable low tolerance for periprocedural complications constitutes what the authors have framed as the 3% Rule of Carotid Stenting.63 How to avoid breaching this rule is central to the theme of patient selection for carotid stenting. The critical all-important task of identifying the standard-risk patient for carotid stenting (not CEA) is discussed later in the chapter.
Prior to recommending carotid stenting as a choice for therapeutic intervention, it is important for both physician and patient to understand the natural history of the condition without intervention, the procedure-related risks (which can immediately erode the benefits of a procedure done purely with the intent of future benefit), and the clinical durability of the stenting procedure.
Over the past decade, one of the most important advances in the field of carotid stenting relates to our understanding of what constitutes “high stent risk.” It is important to remember that CEA was first performed in the 1950s, and over the course of the next several years, surgeons identified both anatomical features and comorbidities that would increase the risk of endarterectomy (high–CEA risk group). Furthermore, these high–CEA risk patients were excluded from participating in the major randomized CEA trials.
To help the interventionist decide whether stenting is an appropriate treatment for a particular patient (and lesion), it is important for the operator to understand, recognize, and differentiate the standard-risk (Box 32-1) from the high-risk CAS patient. This determination, based on an individualized analysis, is the single most important element of the CAS risk stratification process and should be performed for every patient. The designation of high stent risk has evolved over time, and in retrospect was a critical component of the learning curve of the early adopters of the CAS treatment modality. Because the attributes that define high CEA risk (Box 32-2) are distinct from those that define high stent risk, a patient who is high risk for CEA does not automatically become suitable (i.e., standard risk) for CAS. The presence of high-risk features for stenting was unrecognized during the early clinical trials and the criteria for inclusion in these trials only specified “high–CEA risk patients,” thus permitting unbalanced comparisons of technique. Hence, the high event rates observed in early high–CEA risk stent registries resulted in large part from the unwitting inclusion of high stent risk patients. With the more recent exclusion of high stent risk patients, a corresponding improvement in procedural outcomes has been noted. For example, by 2005 the concept of high stent risk was better established, and in the second half of the CREST study, many of these high-risk stent patients were generally excluded (since the CREST protocol written in the late 1990s did not specifically call out high stent risk exclusions).39 The Asymptomatic Carotid Trial (ACT-I), a trial that specifically excludes high stent risk patients, is in progress (NCT00106938).
CCA, common carotid artery; ECA, external carotid artery; EDV, end-diastolic velocity; ICA, internal carotid artery; LV, left ventricular; PSV, peak systolic velocity; TIMI, Thrombolysis in Myocardial Infarction.
Although carotid stenting outcomes are not influenced by gender, age is a very important determinant. The concept of brain reserve is akin to cardiac reserve—a patient with poor left ventricular (LV) function is more likely to manifest and experience complications related to a percutaneous coronary intervention (PCI) or CABG procedure. Similarly, a patient with compromised brain function (diminished brain reserve) is more likely to clinically manifest neurological events related to periprocedural embolization. Embolization is a universal occurrence with all CAS procedures and happens despite the use of EPDs. Patients with prior large strokes, multiple small strokes, or lacunar infarcts and those with dementia are examples of patients with compromised brain reserve. Dementia in particular is a problem. Despite having a perfectly acceptable angiographic and clinical result (i.e., no procedure-related events) in the follow-up period, anecdotal reports suggest a marked deterioration in memory and other cognitive functions. The reason for this is unclear, but dementia should be considered at least a relative contraindication for CAS.
Close attention should be paid to the end-diastolic ultrasound flow velocity. If this value exceeds 100 cm/s (especially >120 cm/s), the angiographic stenosis severity will exceed 80% (as defined by the NASCET criteria; Fig. 32-1) and will meet the treatment threshold for treating asymptomatic lesions.
Ideal lesion (A) has high-grade (>80%) internal carotid artery (ICA) stenosis (enddiastolic velocity 124 cm/s). Note that ICA/external carotid artery angle is acute, and the artery cephalad to stenosis is free of significant bends. B, Same lesion following carotid stenting using a distal embolic protection device (EPD [filter]).
Figure 32-2 illustrates lesion and vessel features that are ideal for stenting using distal embolic protection. These features include:
• A narrow acute angle between the ICA and external carotid artery (ECA). The wider this bifurcation (i.e., the angle approaches 90 degrees or is frankly obtuse), the greater the technical difficulty in advancing a distal embolic protection filter device with a fixed-wire system (Fig. 32-3). The technical difficulty imparted by an open ICA/ECA angle is compounded if there is additional tortuosity in the ICA distal to the stenosis (Fig. 32-4).
• Minimal calcification and no ulceration. Some degree of calcification is nearly ubiquitous in a diseased carotid bifurcation, but heavy concentric calcification in association with a severe stenosis is a major problem. Although the demonstration of carotid calcification is straightforward and requires only fluoroscopy (Fig. 32-5), the distinction between deep vessel wall calcium and superficial calcium encroaching on the vessel lumen may be difficult, and the decision to declare the case unsuitable for CAS is largely subjective. We arbitrarily define heavy calcification as calcification 3 mm or more in width, with concentricity defined by imaging in two orthogonal views. The unyielding nature of calcium, along with the stiffness it imparts to the involved vessel segment, makes it difficult to predilate and advance the EPD and stent delivery system through the lesion (especially the stent). Forcing these devices in an attempt to cross the stenosis not only increases the chances of prolapsing the sheath out of the CCA, it also increases the risk of embolization, spasm, and dissection. Inability to completely dilate and expand the deployed stent despite using larger and/or high-pressure balloons (resulting in a stent with an hourglass appearance) is an intraprocedural nightmare.
• The artery, especially cephalad to the stenosis, is free of any significant kinks or bends. Presence or absence of this key unfavorable feature is extremely important to note on preprocedure magnetic resonance angiography (MRA), computed tomographic angiography (CTA), or invasive angiography, since it increases the degree of difficulty when attempting to place a distal filter EPD. Excessive vascular tortuosity is defined as two or more bend points that are 90 degrees or greater (see Fig. 32-4). At times the tortuosity can be extreme and may impart a hairpin bend to the ICA (see Fig. 32-4). Worsening grades of tortuosity increase the difficulty when attempting to cross the stenosis and may make device delivery difficult or impossible. Straightening of the tortuous vessel segment by stiff wires or devices may result in vessel spasm and reduced antegrade flow. Thus, despite filter placement, the patient does not receive the benefit of brisk antegrade flow and may manifest ischemic symptoms in the absence of adequate collaterals. Additionally, slow flow increases the risk of fibrin deposition within the filter. The longer the dwell time of the EPD, the higher the risk of an iatrogenic thrombus. Iatrogenic tortuosity can also be introduced by placement of the sheath in a redundant carotid artery, so tortuosity should be assessed after the sheath is in place below the carotid bifurcation.
Stenosis severity and eccentricity/concentricity are not problems as long as the flow in the vessel is normal (Thrombolysis in Myocardial Infarction [TIMI] grade III). A severe stenosis in association with less than TIMI III flow (string sign, Fig. 32-6) and an occluded artery are contraindications (Fig. 32-7) for CAS. Ulceration is often noted, even on angiograms from asymptomatic patients, and although not a contraindication, operators should be aware that the risk of embolization might be higher, particularly during the phase of poststent balloon dilation. Angiographic filling defects that are consistent with a thrombus are a contraindication to CAS (Fig. 32-8). Note that both calcium and thrombus may appear as filling defects, and the differentiation is based on the clinical presentation. Whereas a filling defect in a symptomatic patient should be presumed to be thrombus (see Fig. 32-7), filling defects in asymptomatic patients are frequently a result of calcium encroaching on the vessel lumen (Fig. 32-9).
A, Unfavorable lesion. Note obtuse internal carotid artery/external carotid artery (ICA/ECA) angle, high-grade eccentric stenosis immediately distal to bifurcation, and ulcer proximal to stenosis near carotid bulb. Vessel distal to stenosis is straight. B, Result can be seen after treatment using an Emboshield (Abbott Vascular, Santa Clara, Calif.) filter. Wire is independent of filter, and negotiating the unfavorable bifurcation and severe eccentric stenosis is far easier with a wire uncoupled from the filter element. Pre-predilation may be needed. Open-cell stent was used to treat the lesion on the bend; this stent design does not introduce any additional bends in ICA post stenting. Care should be taken to place proximal end of stent flush with origin of ICA. If it hangs between ICA origin and common carotid artery (CCA), stent edge can cause problems in advancing postdilatation balloon as well as filter retrieval catheter. Note that ulcer is excluded, not obliterated, and no attempt should be made to obliterate ulcer by using larger balloons. Flow to ulcer crater will seal off in time.
As a rule, unfavorable anatomical features (Figs. 32-10 and 32-11; also see Figs. 32-3 through 32-9) should be considered contraindications for CAS. Although special techniques (e.g., use of a heavy-gauge buddy wire to straighten tortuous vessel segments, use of cutting balloons to dilate unyielding lesions) may result in a satisfactory angiographic outcome, the risk of a procedure-related neurological event should be presumed to breach the accepted periprocedural complication threshold.
Figure 32-10 Unfavorable vessel morphology for carotid stenting.
A, Complex lesion. There is an obtuse internal carotid artery/external carotid artery (ICA/ECA) angle as well extreme tortuosity of the ICA distal to the stenosis. Note the carotid stent in the contralateral carotid artery. B, Final result after carotid artery stenting. This lesion was treated using a Percusurge GuardWire (Medtronic, Minneapolis, Minn.) distal occlusion balloon for embolic protection and an open-cell stent. Distal filters are contraindicated. Proximal flow reversal is an option, provided the arch anatomy is favorable for placing larger French-size catheters in the carotid artery. This type of vessel morphology will be technically challenging and should be a contraindication for the beginner and low- and medium-volume operators.
Figure 32-11 Classification of the aortic arch.
In the frontal projection, a horizontal line is drawn across the origin of the left subclavian artery. Type I: all the great vessels originate at same level and meet this line. Access to left carotid and innominate arteries is easiest with this aortic arch configuration. Type II and type III: as the aorta becomes more unfolded and elongated (a function of increasing age and hypertension), origin of great vessels becomes displaced more posteriorly, and on the frontal projection, origins are progressively displaced inferior to the horizontal line referenced above. Access becomes increasingly difficult because a catheter approaching from the descending aorta tends to prolapse into the ascending aorta.
Durability is defined by the ability to reduce the risk of a future stroke (the reason why these procedures are performed) and by the frequency of in-stent restenosis (discussed later in this chapter.)
Except in rare instances, nearly all carotid revascularization procedures are elective, and there is no justification for an ad hoc carotid procedure (e.g., combining a carotid intervention with another scheduled invasive procedure such as coronary angiography). A comprehensive history and physical examination, including a detailed neurological exam, are mandatory first steps when evaluating a patient for a possible carotid intervention. Often, patients referred for treatment of “symptomatic” carotid artery stenosis have other reasons for their symptoms, including posterior circulation (vertebrobasilar) disease, cardiac arrhythmias, or a cardioembolic source (e.g., a patient with atrial fibrillation with a clot in the atrial appendage). These patients have incidental (i.e., asymptomatic) carotid disease; the risk assessment and approach to treatment of these patients are very different from the patient with true symptomatic carotid artery stenosis. A formal neurological consultation and additional diagnostic imaging are often helpful in sorting out these patients.
Another frequently encountered problem relates to suboptimal images that result in unreliable noninvasive diagnostic studies (carotid duplex ultrasound and MRA). Whereas quality and reliability of a duplex ultrasound study are very technician dependent, quality of the MRA study is influenced not only by the generation status of the equipment but also by the scanning protocol (with or without gadolinium), the correct timing sequence, and the skill and experience of the interpreting radiologist. It is critical that the ultrasound evaluation be performed in an Intersocietal Commission for the Accreditation Vascular Laboratories (ICAVL) certified laboratory. These considerations are especially important in the patient with asymptomatic carotid artery disease. We strongly recommend that a knowledgeable family member be present during the initial patient interview and subsequent interactions. Besides the science and rationale for the procedure, the discussion should also include regulatory approval and reimbursement status.
The goal of the clinical examination (history, physical including a neurological evaluation) and diagnostic testing (noninvasive as well as angiography) is to provide answers to the following questions/issues:
Patients who consent to brachiocephalic angiography and possible stent placement should undergo a comprehensive clinical cardiovascular evaluation to assess for presence of coronary artery disease(CAD), aortic stenosis, and LV dysfunction. The presence of these comorbidities will impact a patient’s tolerance of the hemodynamic effects of CAS. All patients should undergo evaluation of the preprocedure neurological status, and baseline NIH, Rankin, and Barthel Stroke Scales should be documented. All symptomatic patients, those with a prior history of stroke, and those with an abnormal neurological examination should have a CT or MRI scan of the brain to document baseline status.
In the clinical protocol, great emphasis is placed on dual antiplatelet therapy before and after carotid stenting. The non-event of stent thrombosis and the low rates of peri- and postprocedural embolic events are predicated upon administration of the correct doses of adjunctive antiplatelet therapy. All patients should receive aspirin, 81 to 325 mg daily, and clopidogrel, 75 mg daily, prior to the procedure and for a minimum of 30 days after the procedure.32 If a patient has not received both aspirin and clopidogrel on a daily basis, we suggest they receive a 600-mg loading dose of clopidogrel at least 4 hours prior to the procedure. If this is not possible, the procedure should be rescheduled. There is no experience using prasugrel in patients undergoing carotid stenting.
The approach to patients who are on chronic anticoagulation with warfarin should be individualized, with the acknowledgement that triple therapy with aspirin, clopidogrel, and warfarin increases the risk of bleeding. Discontinuing warfarin while the patient is on dual antiplatelet treatment may be acceptable in patients at low risk for systemic embolism. If the patient requires anticoagulant therapy because of a high risk of thromboembolism, such as a prosthetic mechanical valve, it is appropriate to discontinue warfarin for approximately 4 days prior to the scheduled invasive procedure, “bridge” the patient with heparin if appropriate, and then restart warfarin on the evening of the carotid stent procedure. In patients requiring warfarin in the poststent period, dual antiplatelet therapy should include 81 mg of aspirin together with 75 mg of clopidogrel. Dual antiplatelet medications maintained for 6 to 8 weeks after carotid stenting is optimal.
Blood pressure and/or heart rate–lowering medications are typically withheld the day of the procedure to avoid excessive bradycardia and hypotension resulting from procedure-related carotid baroreceptor stimulation. Postprocedure, blood pressure and heart rate should be followed closely and medications reintroduced as soon as the clinical situation permits. In patients with restenosis following prior CEA (denervated carotid bulb) or in cases where the location of the stenosis is such that balloon inflations and stent deployment are clearly cephalad to the carotid bifurcation, there may be no need to discontinue these medications. In these patients, postprocedural blood pressure requires careful management to minimize the risk and/or consequences of cerebral hyperperfusion syndrome (discussed later).
The current technique of carotid angioplasty and stenting described here has been adopted (with minor modifications) by most high-volume carotid angioplasty centers. Angiography and stenting are performed under local anesthesia. Heart rate and rhythm, blood pressure, and neurological status should be closely monitored throughout the intervention.
Femoral artery access is the preferred and recommended approach. Carotid interventions via brachial or radial artery approach have been described in patients with so-called hostile anatomy of the aortic arch. Direct percutaneous puncture of the carotid artery as a method of vascular access has, for the most part, been abandoned. The frequent need for general anesthesia, proximity of the access site to the site of the lesion, problems related to local hematoma including the risk of airway compromise, and difficulty in compressing a superficial stented vessel for securing hemostasis are some of the reasons why direct carotid artery catheter insertion is no longer used. Femoral venous access is unnecessary unless a reliable peripheral venous access is unavailable. Routine prophylactic placement of a temporary venous pacemaker is no longer recommended but should be readily available.
It is mandatory to have a high-quality complete diagnostic cerebral and extracranial carotid angiogram prior to initiating the stenting procedure. Imaging of the aortic arch by angiography, MRA, or CTA may be helpful to define the arch type and anomalous origins of the vessels. The most common anomaly, seen in approximately 7% of patients, is independent origin of the left vertebral artery from the arch and origin of the left carotid artery from the innominate. Figure 32-12 shows classification of the aortic arch.
A complete cerebral angiogram requires anatomical definition of both intracranial and extracranial carotid arteries as well as the dominant vertebral artery. The decision to perform selective cannulation and angiography of the vertebral artery should be individualized. The vertebral arteries frequently have a tortuous course, and the vessel is prone to spasm—features that predispose to dissection with catastrophic sequelae. It is important for the operator to understand the collateral circulation to the brain hemisphere of interest. Clear definition of the collateral circulation is especially important if a flow-arresting balloon occlusion–type EPD is being considered. Interrupting antegrade flow in the absence of good collateral circulation may cause the patient to have a seizure and require rapid premature deflation of the occlusion balloon. Interruption or even termination of the procedure under these circumstances increases the risk of periprocedural complications.
A variety of catheters are available for diagnostic cerebral angiography, and selection is tied to operator familiarity and experience. Examples of diagnostic catheters are shown in Figure 32-13. It should be understood that catheters that require additional manipulations to reshape them within the ascending aorta increase the risk of embolization. Use of such catheters should be reserved for negotiating the difficult aortic arch anatomy (e.g., patients with extended, stiff, calcified aortas [see Fig. 32-12, type III arch]) when use of alternative preshaped catheters that require less manipulation have either failed or are expected to fail.
Luminal diameter at site of greatest narrowing is recorded in three planes and used as the numerator (a). A reference diameter is taken across a plaque-free section of internal carotid artery distal to stenosis (b) and is used as the denominator. A percentage stenosis is then calculated.
(From North American Symptomatic Carotid Endarterectomy Trial. Methods, patient characteristics, and progress. Stroke 22:711–720, 1991.)
Diagnostic angiography involves injection of 2 to 3 mL of nonionic contrast diluted with an equal amount of saline. Immediately prior to acquisition of the subtraction angiogram, patients are asked not to breathe, move, or swallow to minimize motion artifact. They are also warned that they may experience a funny taste and may see flashing or multicolored lights in the ipsilateral eye.
Diagnostic angiography consists of visualization of the origins of the innominate and left common carotid arteries from the aortic arch (by selective injections), both carotid bifurcations in orthogonal projections, and both vertebral arteries (usually by nonselective injections). Intracranial images of both carotid arteries are routinely acquired, and occasionally selective injection of one or both vertebral arteries is also performed. Brachiocephalic angiography has several advantages:
2. It demonstrates anatomical conditions that can be unfavorable for carotid stenting. Examples include dilated/extended aortic arch (see Fig. 32-12), marked vessel tortuosity, heavily calcified stenosis, and lesions with obvious filling defects (see Figs. 32-3 through 32-11).
3. It helps define the status of collateral circulation to the ipsilateral cerebral hemisphere (i.e., the one supplied by the stenotic carotid artery being evaluated for treatment). Knowledge of contralateral carotid stenosis or occlusion and status of the collateral supply influences the stenting technique: shorter balloon inflations, for example, and choice of protection device—flow interrupting (occlusion balloon) vs. flow preserving (filter devices). The term isolated hemisphere describes the anatomical situation where the cerebral hemisphere of interest is entirely dependent on the ipsilateral ICA for its blood supply, owing to absence of the anterior and posterior communicating arteries.
4. It reliably demonstrates significant flow-limiting stenosis distal to the carotid bifurcation. Although the bifurcation stenosis may be treatable, the ultimate benefit of stroke reduction may not accrue to the patient because of additional cephalad disease.
The main risks of invasive cerebral angiography relate to the use of contrast and the possibility of a neurological event. The typical sequence of acquisition and the usual angiographic views are listed in Box 32-3.
The bifurcation is imaged in LAO 45-degree as well as lateral projections. If the bifurcation is “overrotated,” an AP caudal view usually separates the external and internal carotid arteries very well.
Once the diagnostic study is completed, the ICA with the target stenosis is identified, and there are no anatomical contraindications for stenting, a 90-cm long, 6 F sheath is advanced into the CCA using one of two techniques shown in Figure 32-14.
Figure 32-14 Carotid sheath placement.
A, In the two-step approach using a diagnostic catheter, a Glidewire (Boston Scientific, Watertown, Mass.) is inserted into external carotid artery (ECA). Catheter is advanced to the ECA, and the Glidewire exchanged for a support wire such as a Supra Core (Abbott Vascular, Santa Clara, Calif.) wire. Catheter is then removed, and sheath with introducer is advanced over support wire to common carotid artery (CCA). Finally the introducer and wire are removed. B,