Stroke is a leading cause of death and disability in the developed world.1 More than 750,000 strokes occur in the US annually,1 and one-third of these patients die during the first few months after their strokes. Acute carotid syndrome (ACS) is defined as a set of signs and symptoms linked to neurological deficits (transient ischemic attack [TIA] or ischemic stroke) caused by carotid occlusive disease (COD).
Without surgery, the 90-day stroke risk for symptomatic extracranial carotid stenosis (>50%) may be as high as 20–30%.2,3 The timing of carotid endarterectomy (CEA) for ACS is a key benchmark for secondary stroke prevention because delays in endarterectomy are associated with an increased risk for recurrent stroke.4 On the other hand, the development of new endovascular technologies—the advent of cerebral embolic protection devices (EPDs)—has improved the procedural safety and clinical outcomes of carotid artery stenting (CAS). Thus, CAS has been proposed as an alternative therapeutic modality for COD because it allows for shorter hospitalization and convalescence after treatment. This article suggests a multidisciplinary, patient-specific treatment strategy for patients with ACS, reviewing the indications and limitations of surgical and endovascular techniques.
Stroke is a devastating disease associated with loss of mobility, independence, and communication, leading to a huge healthcare costs and lost productivity. Patients present with a wide variety of symptoms depending on the vascular territory involved, the amount of clot present, and the presence or absence of collateral vessels. Common symptoms include weakness, dizziness, blurred vision or visual loss, speech and comprehension problems, and, finally, cognitive impairments.
Unstable Atherosclerotic Plaque Presentation
Atherosclerosis is a diffuse process with underlying chronic inflammation that involves vascular, metabolic, and immune factors, which may lead to plaque vulnerability. There are several types of dangerous plaque believed to cause neurological symptoms. Plaque rupture expressing tissue factor, resulting in thrombus formation, occurs when the constituents of the plaque are exuded into the circulation.5 A thrombus can also occur on a de-endothelialized (ulcerated) but otherwise intact plaque5 (see Figure 1). This may lead to hemodynamic compromise due to vessel occlusion, even without a plaque rupture.5 Another possibility is to have thrombus on the nidus of a calcified nodule that projects into the circulation and may act as a ‘lightning rod’ for thrombus formation, embolizing and causing a cerebrovascular event.5 A final possibility is a thrombus forming within the plaque, leading to further carotid stenosis and hemodynamic compromise.
Prospective studies with ultrasound found that an echogenic plaque has a lesser risk for stroke than a lipid-filled echolucent plaque.6 Other investigators have looked at carotid intima medial thickness (IMT) as a marker for vulnerability to future cardiovascular events.7 Carotid IMT is now a well-recognized indicator for atherosclerotic disease development in carotid arteries.7 Conventional arteriography was considered the gold standard for diagnosis of acute carotid syndromes, but it under-represents the atherosclerotic burden of the aortic arch and exposes the patient to a measurable risk for stroke. Contrast-enhanced computed tomography (CT) axial images are obtained to include the ascending and descending aortic arch. The 3D CT angiographic analysis of the aortic arch, common carotid artery (CCA), and internal carotid artery (ICA) is a non-invasive diagnostic tool for treatment planning. Useful information can be gleaned from axial CTA images, but tortuosity and lengths are much better evaluated with some type of 3D rendering. Magnetic resonance imaging (MRI) does not easily depict calcium, whereas CT scans do. Currently, there is no commercially available MR program that characterises carotid plaque components.
Timing of Revascularization
The optimal timing of elective CEA in ACS, particularly after a recent minor stroke, remains controversial. Early surgery (within 30 days after stroke) of a stenotic but patent ICA has been associated with the fear that ICA revascularization might convert non-hemorrhagic infarction into a hemorrhagic one, or at least cause an enlargement of the infarction zone.8–10 Therefore, the strategy to delay surgery after a recent stroke for four to six weeks has been accepted in clinical practice for many years. Ballotta et al.11 showed that early CEA (<30 days) after a minor stroke can be performed safely with a total peri-operative mortality and morbidity of 2%, which was similar to that seen in the control group undergoing delayed CEA. Piotroski et al.12 found no significant difference in the incidence of cardiovascular events and deaths between patients operated on sooner or later than six weeks after their stroke.
Potential reasons for delays to CEA include patient factors (delayed symptom recognition and presentation to medical attention), physician factors (delayed diagnosis and referrals), and resource availability (rapid access to vascular imaging).11 A time-dependent benefit was particularly evident in patients with moderate (50–69%) symptomatic carotid stenosis. In this patient sub-population, CEA was beneficial if performed within the first two weeks, but the benefit was lost when surgery was delayed for more than three months.11
Large randomized clinical trials from the early 1990s have shown the superiority of CEA and aspirin therapy in preventing stroke compared with aspirin therapy alone for the treatment of symptomatic COD.13–15 On the basis of these trials, the most recent American Heart Association (AHA) guidelines recommended CEA for symptomatic patients with a stenosis of 50–99% if the peri-operative risk for stroke or death is <6%.13–15
Surgery and Carotid Stenting
Due to recent advances in endovascular techniques, CAS can now be considered as an alternative treatment for COD. Moreover, as institutions and operators have gained more experience with CAS, the likelihood of treating more challenging anatomy and potentially sicker patients is expected. CAS has the added benefit of being a less invasive procedure, potentially minimizing the risks of wound complication and cranial nerve injury.
In addition, this may translate to shorter lengths of hospitalization and less resource utilization.16 CAS can also be considered as a first-line treatment in cases of tandem stenosis, hostile necks after radiation, or clopidogrel administration due to drug-eluting stent placement linked to potential operative bleeding.
A number of randomized controlled trials designed to test the non-inferiority of CAS versus CEA have been conducted.17–20 However, due to a number of methodological and statistical problems, drawing any definitive conclusions is still problematic and the use of CAS remains controversial. Criteria used to evaluate each patient’s suitability for CAS were largely subjective and not prospectively standardized. Consideration was given to the degree of atherosclerosis and tortuosity present in the aortic arch, ipsilateral CCA, and ICA that would complicate the placement of a sheath, stent, or distal EPD. Examples of such hostile anatomy would include significant CCA stenosis, short CCA with external carotid artery (ECA) occlusion, or 180° bends in the CCA or ICA. Unfavorable anatomies include elongated or type III aortic arch configurations, circumferential calcification of the bifurcation lesion, or long lesions requiring more than one stent (see Table 1). On the other hand, favorable morphology is type I aortic arch configuration.
Several studies have evaluated the relationship between the characteristics of the plaque and the presence or absence of neurological symptoms or cerebral CT lesions. Biasi et al.21 suggested a correlation between plaque characterization and clinical features. The use of a quantitative computer-assisted index of echogenicity, such as grayscale median (GSM), allows measurement of the plaque echolucency, which may identify the carotid plaque related to a higher risk for stroke during CAS. The Imaging in Carotid Angioplasty and risk for Stroke (ICAROS) registry assessed the role of GSM as a useful indicator of the embolic potential of the carotid lesion.21 Finally, pre-operative defined echographic criteria allow for the better selection of candidates for CAS. Limitations of the suggested plaque analysis include the reproducibility of the GSM measurements.
Flexibility and scaffolding are key characteristics derived from stent design. Closed-cell stents are less flexible and may develop kinks in a tortuous ICA. Conversely, stents with an open-cell configuration conform best to angulated vessels or tortuous anatomy. Scaffolding refers to the amount of support given to the vessel wall by a stent. This may, hypothetically, be important in the case of vulnerable plaques, where insufficient scaffolding may cause distal embolisation and stroke if plaque material is squeezed through the struts of the stent. Closed-cell stents could potentially offer maximal scaffolding to the vessel wall. In approximately 75% of all CAS procedures, either open-or closed-cell stents may be used indiscriminately.22,23 For the remaining patients, careful pre-operative screening is recommended. Cerebral protection devices have been proposed as a useful adjunct to limiting micro-emboli formation after CAS. In the SAPPHIRE trial,18 CAS with EPD resulted in a major ipsilateral stroke rate at one year of 0.6%, a minor ipsilateral stroke rate of 3.8%, and a minor non-ipsilateral stroke rate of 1.9%, confirming that intra-operative EPD deployment does not eliminate embolic risk, at least for the current generation of EPDs.18
Octogenarians continue to be a high-risk group for CAS.24 The increased risk for stroke and death after endovascular treatment in this patient population has called into question the utility of treating these patients. One hypothesis of the limited success of CAS in this patient group might be the occurrence of more calcified aortic arches and ‘shaggy aorta,’ more challenging anatomy, and less tolerance to ischemic insults caused by higher incidences of micro-emboli. In this context the Stent-protected Percutaneous Angioplasty versus Endarterectomy of Symptomatic Carotid Artery Stenosis (SPACE) trial suggests that older patients (>68 years of age) are best treated with surgery.20 The initial SPACE report failed to show non-inferiority of stenting for symptomatic stenosis, considering peri-procedural (<30 days) rates of stroke and death.20 The two-year results of the SPACE study were recently presented at the 2009 International Stroke Conference of the American Heart Association and showed that the combined rate of stroke and death continues not to differ between the two treatments. The increased restenosis rate in the patients who underwent stenting is significant, although the long-term effects of this are yet to be determined.
The International Carotid Stenting Study (ICSS) compared stenting with endarterectomy in patients with symptomatic carotid stenosis >50% within six months prior to randomisation. Patients were enroled from 50 centers in 15 countries in Europe, Canada, Australia, and New Zealand. Primary safety data on the 30-day rate of stroke, myocardial infarction, or death were presented at the 2009 European Stroke Conference. CEA showed superiority over CAS and remains the treatment of choice for suitable patients with symptomatic COD, at least in cases treated in <30 days.
ACS has a remarkable risk for motor and cognitive impairments. Patient selection, procedural timing, choice of therapeutic strategy, and technical skills are essential to achieve optimal outcomes. An aggressive approach is justified in order to reduce the occurrence of a new disabling stroke. CAS is a less invasive therapeutic option, but more scientific data are needed. Surgical and endovascular techniques are complementary and not controversial. The best way forward for treatment is to focus on patient-specific characteristics such as plaque morphology, aortic arch, and carotid anatomy, as well as comorbidities. A multidisciplinary outlook avoids decisions based on competing speciality interests or according to technology availability alone.