Eversion Carotid Endarterectomy

Eversion carotid endarterectomy (eCEA) involves oblique transection of the internal carotid artery (ICA) at its origin at the carotid bifurcation, followed by extirpation of the plaque by means of eversion and subsequent reimplantation of the ICA into the carotid bulb. It has been validated in randomized and nonrandomized prospective studies as a safe and effective surgical treatment for carotid stenosis. The efficacy of surgical treatment of atherosclerotic carotid stenosis in the prevention of stroke is well documented.

Worldwide, stroke is a leading cause of mortality; cerebrovascular disease accounted for approximately 7.44 million deaths in 2021. ^[1] In the United States, the annual incidences of stroke and transient ischemic attacks (TIAs) are approximately 795,000 and 300,000 cases, respectively, and stroke was responsible for approximately 163,000 US deaths in 2021. ^[1]

Stroke is an important cause of long-term disability. ^[2]  Only 29% of patients with nonfatal stroke recover with normal neurologic function. ^[3] In the Framingham study, which prospectively followed 5184 men and women from the general population for 26 years, Sacco et al reported a very high incidence of recurrent cerebrovascular infarctions (9% per year) in patients who survived an initial stroke. In the same study, the cumulative 5-year recurrent stroke rate was 42% for men and 24% for women. ^[4]

In addition to high rates of death, recurrence, and long-term disability, management of stroke imposes a substantial economic burden on society. The annual health care expenditure directly and indirectly related to stroke in the United States is greater than $56 billion. ^[1]

In routine clinical practice, indications for the treatment of patients with carotid stenosis are based on the presence of symptoms and the degree of stenosis. ^[5]

In 2022, the Society for Vascular Surgery (SVS) issued updated evidence-based clinical practice recommendations for the management of carotid stenosis. ^[6]  The SVS guidelines recommended carotid endarterectomy (CEA) as the treatment of choice for low-risk symptomatic patients with carotid artery stenosis greater than 50% and low-risk asymptomatic patients with carotid artery stenosis greater than 70%. ^[6] Generally, carotid surgery is performed if a patient’s perioperative stroke or mortality risk is less than 3% and the life expectancy is greater than 5 years.

In 2023, the European Society for Vascular Surgery (ESVS) issued updated guidelines for the management of atherosclerotic carotid and vertebral artery disease. ^[7]

The reference standard for calculation of the degree of carotid artery stenosis is based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria (see the image below). In this approach, the smallest residual lumen at the level of stenosis is compared with the normal distal ICA lumen by means of catheter-based arteriography.

North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Convention for describing carotid stenosis is to compare lumen diameter at most narrow point to diameter of internal carotid artery in normal segment several centimeters distal to stenosis.

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An alternative (though one that is less frequently used during catheter-based arteriography) is to determine the degree of the carotid artery stenosis by using the European Carotid Surgery Trial (ECST) criteria. In the ECST approach, the smallest residual lumen at the level of stenosis is compared with the local estimated diameter of the carotid bulb.

A 70% carotid stenosis calculated according to the NASCET criteria corresponds to an 85% carotid stenosis calculated according to the ECST criteria. By the NASCET criteria, moderate stenosis is defined as 50-69% stenosis and severe stenosis as 70-99%. By the ECST criteria, the corresponding values are 75-84% for moderate stenosis and 85-99% for severe.

Duplex ultrasonography (US) is the imaging modality of choice for the diagnosis of carotid artery stenosis (see the image below); it is safe, quick, and reliable in experienced hands. However, the accuracy of duplex US is highly operator-dependent. In addition, factors that affect flow velocities, such as severe contralateral ICA stenosis or occlusion, can cause compensatory elevations of velocity and result in overestimation of the degree of stenosis.

A. Arterial flow (red) is displayed in internal carotid artery (ICA) and common carotid artery (CCA). Sampling for flow velocities and spectral waveform analysis is carried out in center stream of ICA, and waveform is shown below. Peak systolic and end-diastolic velocities are measured on representative wave. B. Same general area is being interrogated in diseased ICA. Lumen appears to narrow, and red color becomes variegated and lighter. Arterial flow is sampled in area of maximal disturbance and narrowing, and resultant waveform is displayed below.

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Computed tomography (CT) and magnetic resonance angiography (MRA) can be used to identify plaque morphology and in cases where US is technically difficult (eg, heavily calcified or high lesions); this can be helpful in planning CEA or stenting (see the image below). ^{[8, 9, 10]}

Representative image of extracranial circulation obtained with CT angiography and 3-dimensional reconstruction. Arrow points to stenosis in left internal carotid artery.

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The underlying etiology of carotid artery stenosis (see the image below) is the formation of atheromatous plaque at the bifurcation of the common carotid artery (CCA) and in the origins of the ICA or, less frequently, the external carotid artery (ECA). ^[11] The temporary or permanent clinical manifestations of carotid artery stenosis (TIA or stroke) result from cerebral hypoperfusion through the embolized artery in most cases, as well as stenosis due to plaque progression in situ. ^[12]

Underlying etiology of carotid artery stenosis is formation of atheromatous plaque at bifurcation of common carotid artery and in origins of internal carotid artery.

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The reduction in the radius of carotid blood vessels has a significant negative effect on cerebral perfusion, in that blood flow through these vessels, as determined by Poiseuille’s law, is directly related to the fourth power of their radius.

Atheromatous plaque not only reduces cerebral blood flow but also represents an irregular surface within the lumen of the carotid artery that is prone to thrombus formation (see the image below). Ulceration and rupture of the plaque create a highly thrombogenic surface that promotes platelet aggregation and creates thromboembolic debris, which subsequently leads to distal arterial embolization.

A. Simplified flow patterns at carotid bifurcation demonstrate complex reversal of flow along posterior wall of carotid sinus. This region is most vulnerable to plaque development. B. Established plaque at carotid bifurcation. C. Soft, central necrotic core with overlying thin fibrous cap. This area is prone to plaque rupture. D. Disruption of fibrous cap allows necrotic cellular debris and lipid material from central core to enter lumen of internal carotid artery, thus becoming atherogenic emboli. Patient may experience symptoms (transient ischemia, stroke, or amaurosis fugax) or remain asymptomatic, depending on site of lodgment and extent of tissue compromise. E. Empty necrotic core becomes deep ulcer in plaque. Walls of ulcer are highly thrombogenic and reactive with platelets. This leads to thromboembolism in internal carotid artery circulation.

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Extracranial cerebrovascular atherosclerosis, which accounts for most carotid artery disease, is responsible for 15-52% of all ischemic strokes. ^{[13, 14]} Hypertension is another important cause of stroke. Other rare entities of carotid artery disease include fibromuscular dysplasia, arterial kinking secondary to elongation, extrinsic compression, carotid body tumors, traumatic occlusion, intimal dissection, and radiation.

The efficacy of surgical treatment of atherosclerotic carotid stenosis in the prevention of stroke has been well documented. ^{[6, 1]}  Level 1 data from several large multicenter clinical trials, as well as data from the National Surgical Quality Improvement Program (NSQIP) database and large multicenter studies, have validated the efficiency and safety of CEA as the treatment of choice for reducing the risk of ipsilateral stroke in both asymptomatic and symptomatic patients with moderate-to-severe carotid artery stenosis. ^{[15, 16]}

In NASCET, the 5-year incidence of ipsilateral stroke was 15.7% in patients with moderate stenosis treated surgically, compared with 22.2% in patients with moderate stenosis who received optimal medical therapy. ^[15] NASCET also demonstrated a cumulative risk of ipsilateral stroke of 26% and 9% at 2-year follow-up in patients treated medically and those treated with CEA, respectively. This reduction in the incidence of stroke in the CEA group was demonstrated in patients with symptomatic, high-grade stenosis (ie, 70-99%).

Similarly, ECST data demonstrated that the 3-year risk of ipsilateral stroke was 2.8% in patients randomized to undergo CEA and 16.8% in those randomized to receive medical therapy alone. ^[16] The 3-year risk of disabling or fatal stroke or death was 6.0% and 11.0% for surgically and medically treated patients, respectively. Both patient cohorts were symptomatic and had high-grade carotid stenosis.

In the Asymptomatic Carotid Atherosclerosis Study (ACAS), a randomized clinical trial from North America comparing best medical therapy with surgery in 1622 asymptomatic patients with carotid artery stenosis, CEA significantly reduced the overall 5-year risk of ipsilateral stroke and any perioperative stroke or death from 11.0% to 5.1% in patients with asymptomatic carotid stenosis greater than 60%. ^[17] This corresponded to a relative risk reduction of 53% and an absolute risk reduction of approximately 1% per year.

Similarly, in the Asymptomatic Carotid Surgery Trial (ACST), a study carried out in Europe, the investigators demonstrated that CEA yielded a significant reduction in the 5-year risk of stroke or death, from 11.8% to 6.4%. ^[18]

Numerous randomized and nonrandomized prospective studies have validated eCEA as a safe and effective method for the surgical treatment of carotid stenosis and have shown it to be characterized by low restenosis rates.

Data from the Eversion Carotid Endarterectomy Versus Standard Trial (EVEREST), which included 1353 patients, demonstrated that eCEA and patch angioplasty had significantly lower restenosis rates when compared with primary closure CEA. ^[19]

A Cochrane review of the literature that included close to 2500 patients from five controlled clinical trials found that eCEA was associated with a lower risk of restenosis than patch angioplasty CEA. ^[20] Data from the same study showed no significant differences between the two groups with respect to the rate of perioperative stroke (1.7% for eCEA and 2.4% for patch angioplasty) and perioperative mortality (2.0% and 1.9%).

In 2014, Ballotta et al published results of a study that evaluated 2007 consecutive primary eCEAs in 1773 patients over 12 years. ^[21] ACAS and NASCET recommendations were used as inclusion criteria for asymptomatic and symptomatic patients, respectively. Of the 2007 procedures, 1446 (72.1%) were performed in patients who were symptomatic at the time of surgery. All procedures were performed by the same surgeon in patients under general anesthesia. Intraoperative electroencephalography (EEG) was used for the assessment of cerebral perfusion and need for the selective shunting.

During the study, ^[21] there were nine (0.47%) asymptomatic late carotid restenoses (six moderate [50-69%] and three severe [≥70%]) and one (0.05%) carotid occlusion. Data from Kaplan-Meyer analysis showed the rates of freedom from restenosis and/or occlusion to be 99.9 ± 0.1% at 1 year, 99.3 ± 0.2% at 5 years, 99.3 ± 0.2% at 10 years, and 99.3 ± 0.2% at 12 years. Data also showed a perioperative stroke rate of 0.4% and no intraoperative mortality. This study demonstrated that eCEA can be performed in both asymptomatic and symptomatic patients with extremely low perioperative morbidity and mortality, as well as low restenosis rates.

A study by Schneider et al, using data from the SVS Vascular Quality Initiative (SVS VQI) database for 2003-2013, found that eCEA and conventional CEA were comparable in terms of freedom from neurologic morbidity, death, and reintervention; that eCEA was associated with significantly shorter procedure times; and that eCEA reduced certain expenses more commonly associated with conventional CEA. ^[22]

In a study of 1385 consecutive cases, Ben Ahmed et al found eCEA to be both safe and cost-effective. ^[23]

In 2018, Paraskevas et al published an updated systematic review and meta-analysis aimed at determining whether eCEA has significant advantages over conventional CEA. ^[24]  They found eCEA to be superior with respect to perioperative outcomes (stroke, death, death/stroke) and late restenosis but did not find a significant difference between it and patched CEA with regard to either early or late outcomes. Their data suggested  that early and late outcomes after conventional CEA are similar to those after eCEA, provided that the arteriotomy is patched.

In a meta-analysis that included 10 studies (N = 3568; 3672 operations) comparing eCEA (n = 1718) with CEA with patch plasty (n = 1954), Gavrilenko et al examined outcomes in the immediate and remote postoperative periods. ^[25] They found eCEA to be associated with a shorter time of carotid artery cross-clamping, a lower frequency of intraoperative temporary bypass, and fewer cases of ischemic stroke in the immediate and remote postoperative periods, as well as fewer instances of restenosis in the long-term postoperative period.

In a multicenter clinical trial (N = 25,106) evaluating long-term (mean follow-up, 124.7 mo) outcomes of eCEA (n = 18,362) against those of conventional CCA (n = 6744), Belov et al found eCEA to be associated with lower frequencies of fatal outcome, cerebrovascular death, nonfatal ischemic stroke, and repeated revascularization because of restenosis greater than 60%. ^[26]

A 2023 systematic review and meta-analysis by Marsman et al did not find conclusive evidence of any significant outcome differences between eCEA and CEA with patch angioplasty in symptomatic patients with 50% or greater stenosis of the ICA. ^[27] However, the data from which these conclusions were derived came from trials with a very low certainty according to GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria; thus, the findings should be interpreted with caution.

The choice of surgical technique for the treatment of carotid artery stenosis should depend on the clinical judgment, experience, and preference of the operating surgeon, in the context of a discussion of the options with the patient.