INTRODUCTION

Stroke was the fifth leading cause of death in the United States in 2020 and the leading cause of long-term disability.1,2 It is estimated that strokes cost nearly $53 billion for the provision of healthcare, medication, and missed workdays in the United States.2 Ischemia is the cause of 87% of strokes with carotid artery stenosis (CAS) contributing to approximately 10% of ischemic strokes.2,3 The identification and treatment of CAS is essential for primary and secondary prevention of stroke. Carotid endarterectomy (CEA) is the gold standard treatment for CAS but may not be feasible in individuals at high-risk for surgical intervention.4 Transfemoral carotid artery stenting (TF-CAS) is a minimally invasive treatment option but has been found to have higher rates of stroke and death in the high-risk population.5 The introduction of transcarotid artery revascularization (TCAR) presents a minimally invasive treatment option for individuals at high-risk for surgical intervention if it provides outcomes consistent with CEA.

Carotid Artery Stenosis

Atherosclerotic plaque formation in the internal carotid artery results in CAS when it becomes hemodynamically significant. As the degree of stenosis increases, the lumen of the internal carotid artery narrows decreasing blood flow to the brain while also presenting the risk of plaque rupture with embolization distally or thrombus formation within the vessel lumen. These complications of CAS present the risk of ischemic stroke. The estimated global prevalence of CAS in individuals aged 30-79 years is 1.5% with an increase of 59.13% from 2000 to 2020.6

A patient with CAS and no neurologic symptoms or with a history of symptoms greater than six months prior is considered asymptomatic.3 Asymptomatic disease is typically identified during physical examination through auscultation of a carotid bruit or incidentally on imaging studies. The presence of acute neurologic symptoms consistent with amaurosis fugax, transient ischemic attack, or stroke that can be linked to CAS is considered symptomatic.3 Amaurosis fugax will occur on the ipsilateral side and motor or sensory deficits on the contralateral side. Presenting symptoms will depend on the area of the brain affected by limited arterial flow.

Evaluation by neurology will be necessary to rule out other causes for the patient’s symptoms.

Neurologic symptoms including dizziness, lightheadedness, syncope, and vertigo are not typically attributed to CAS as they are symptoms associated with the posterior circulation, while the internal carotid artery blood flow favors the anterior and middle cerebral arteries.3

Diagnostic Imaging

Carotid duplex ultrasound is considered the first-line evaluation for CAS. Utilized as a screening examination, ultrasound can provide quantification of the degree of stenosis through blood flow velocities in the arterial lumen.3 A velocity of 230 cm/sec or higher is consistent with arterial luminal stenosis of 70% or greater.3 Computed tomography angiography (CTA) provides a more defined evaluation by quantifying the degree of stenosis and characterizing the morphology of the carotid plaque to support medical decision making and surgical planning.3

Clinical Practice Guidelines

The Society of Vascular Surgery (SVS) recommends screening for asymptomatic CAS in patients at increased risk due to comorbid conditions shown in Table 1.7 In asymptomatic patients, CEA is recommended for stenosis of greater than 70% with less than 3% risk of perioperative stroke and death and a life expectancy of at least 3 years.7 Symptomatic patients are recommended to undergo CEA with stenosis of 50% or greater.7 Carotid artery stenting should be considered in patients at high-risk for surgical intervention with CEA.7

7

Table

Presence of lower extremity peripheral arterial disease

Those undergoing coronary artery bypass surgery

Age 55 or greater with two atherosclerotic risk factors

Age 55 or greater and current cigarette smoker

Presence of diabetes, hypertension, or coronary artery disease

Presence of silent cerebral infarction on imaging studies

Surgical Treatment

Surgical management of CAS cannot reverse the effects of a neurologic event but is a preventative measure for long-term stroke prophylaxis. Determination of those appropriate for surgical intervention includes consideration of the degree of stenosis, symptom status, preoperative stroke risk, life expectancy, anatomic risk including contralateral carotid occlusion or prior neck irradiation, and cardiovascular comorbidities that present a physiologic risk.4 CEA remains a wellestablished treatment option for CAS but presents a risk for post operative mortality in those with increased age, contralateral carotid artery stenosis, congestive heart failure, chronic kidney disease, diabetes, and chronic obstructive pulmonary disease.3,8 The Centers for Medicare and Medicaid Services (CMS) has outlined specific physiologic and anatomic high-risk criteria for patients under consideration for CEA shown in Table 2.

Congestive heart failure class III/IV

Left ventricular ejection fraction <30%

Unstable angina

Contralateral carotid occlusion

Recent myocardial infarction

Prior CEA with recurrent stenosis

Prior neck radiation

Evaluation of CEA outcomes from the American College of Surgeons National Surgical Quality Improvement Program database compared patients meeting CMS high-risk criteria guidelines against those determined to be normal risk.4 The exact physiologic or anatomic highrisk factor was unknown to reviewers. Patients with physiologic risk factors were older with higher rates of hypertension, congestive heart failure, diabetes, and chronic kidney disease.4 Those with anatomic risk factors were more likely to have comorbidities including congestive heart failure, chronic obstructive pulmonary disease, and end stage renal disease on hemodialysis.4

High-risk patients were found to have higher rates of adverse events in the first 30 days following CEA than those at normal risk. In 25,788 patients who had undergone CEA, those meeting high-risk physiologic criteria had twice the rate of stroke/death (4.6 vs 2.3%, p<.001) and nearly twice the rate of perioperative cardiac events (3.1 vs 1.6%, p<.001).4 High-risk anatomic patients had elevated rates of stroke/death (3.6 vs 2.3%, p<.001), perioperative cardiac events (2.3 vs 1.6%, p<.01), and cranial nerve injury (4.3 vs 2.5%, p<.001).4 When separated into symptomatic or asymptomatic presentation, those meeting high-risk physiology criteria who presented asymptomatically had a stroke/death rate significantly higher than normal risk patients (4.7 vs 1.5%, p<.001), well above the 3% recommended in the SVS clinical practice guidelines.4 Individuals meeting high-risk CMS criteria demonstrated worse outcomes than those deemed normal risk with differences in stroke/death rate significantly affected by individuals presenting asymptomatically and with high-risk physiology.

Identifying a minimally invasive treatment option to effectively treat individuals meeting high-risk CMS criteria with comparable outcomes to CEA has been challenging. The introduction of TF-CAS was intended to meet this aim but has not found widespread acceptance due to a higher risk of poor outcomes. The differences in major adverse event outcomes compared to CEA are well documented in the literature with historical studies noting higher rates of stroke following TF-CAS and dramatic increases in those treated for symptomatic CAS.10 One study of 9,753 patients identified a statistically significant higher rate of stroke and death in the perioperative period for symptomatic patients treated with TF-CAS (OR 1.70, 95% CI 1.31 to 2.19; p<0.0001). In asymptomatic patients the rate was found to be higher but not statistically significant.11

The increased rate of stroke and death in TF-CAS patients is likely associated with the point of access that requires an extensive path to be traversed to enter the treatment site. Through a transfemoral artery approach, the guidewire must pass through the aorta and its arch, into the common carotid artery, and up to the internal carotid artery. In high-risk patients, the aorta may be diseased and tortuous creating significant risk during the procedure due to the lack of a protective device during access. Prior to carotid stent placement, an embolic protection device is passed through the stenotic area resulting in the risk of plaque fracturing and thrombus embolization leading to potential ischemic stroke.12 This risk was proven through the utilization of transcranial doppler ultrasound in the operative suite documenting microembolic events during carotid stent placement.13

Transcarotid Artery Revascularization

A new procedure has been developed to overcome the complications associated with TF-CAS. TCAR is a minimally invasive procedure utilizing direct access at the common carotid artery proximal to the stenosis and employs an embolic protection device to reverse flow in the carotid artery.10 Embolic risk is minimized as the protection device is placed and flow reversal initiated prior to crossing the stenotic area and is utilized throughout the procedure.10 The embolic protection device functions as an arteriovenous circuit between the carotid artery and femoral vein and contains a filter to capture microemboli.10

TCAR avoids the high risk maneuvers completed during TF-CAS, including traversing the aortic arch, cannulation of the common carotid artery at the arch, and crossing the stenotic area without embolic protection.10 Advantages of TCAR include a smaller incision and operative times around 30 minutes less than CEA, contrast volume around 50% of that needed for TFCAS, and in some institutions the procedure is completed under local or regional anesthesia.10 If TCAR can provide improved outcomes compared to TF-CAS and similar outcomes to CEA, this would provide potential protection to patients who meet CMS high-risk criteria for surgical intervention by CEA.

Comparison of Outcomes

In 2015, TCAR received approval from the United States Food and Drug Administration and CMS with plans for a transcarotid artery revascularization surveillance project. The surveillance project is ongoing with an estimated completion date of December 2024.14 No randomized control trials have been conducted at this time to assess TCAR effectiveness or outcomes.

Transfemoral

carotid artery stenting. Utilization of the SVS Transcarotid Artery

Revascularization Surveillance Project database and the Transfemoral Carotid Artery Stent Registry in one study, including 3,286 patients in each cohort, compared outcomes for the procedures.8 Those undergoing TCAR demonstrated a significantly lower in-hospital risk of stroke (1.3% vs 2.4%; absolute difference, -1.10% [95% CI, -1.79% to -0.41%]; RR, 0.54 [95% CI, 0.38 to 0.79]; p=.001) and death (0.4% vs 1.0%; absolute difference, -0.55% [95% CI, -0.98% to –0.11%]; RR, 0.44 [95% CI, 0.23 to 0.82]; p=.008).8 There was no statistically significant difference in myocardial infarction or transient ischemic attack.8 Follow up after one year revealed a statistically significant difference in ipsilateral stroke and death rates in TCAR patients compared to their transfemoral counterparts (5.1% vs 9.6%; hazard ratio, 0.52 [95% CI, 0.41 to 0.66]; p<.001).8 Similar results have been found in other studies documenting better outcomes for TCAR compared to TF-CAS both perioperatively and long-term.15,16 SVS guidelines now state that TCAR is superior or preferable to TF-CAS in individuals meeting CMS high-risk criteria.7

Carotid endarterectomy. A systematic review and meta-analysis of six studies evaluated outcomes for TCAR compared to CEA.17 No statistical significance was found in stroke or death rates (n = 14,026, OR 1.03, 95% CI 0.77-1.37, p=0.84) and (n = 14,200, OR 1.14, 95% CI 0.67-1.94, p=0.63) respectively.17 The incidence of postoperative myocardial infarction was lower in the TCAR cohort (n = 14,174, OR 0.55, 95% CI 0.36-0.83, p=0.004).17 These results did not change when patients were separated into symptomatic and asymptomatic cohorts.17

Comparable results were achieved in two other studies supporting these findings.10,15 TCAR patients were found to experience a lower rate of cranial nerve injury compared to individuals undergoing CEA (n = 4,012, 0.54% and 1.84%, OR: 0.52, 95% CI: 0.36, 0.74).15

Review

of the SVS Transcarotid Artery Revascularization Surveillance Project

noted patients undergoing TCAR compared to those receiving CEA were older and had more comorbidities including coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and on hemodialysis.10 The TCAR patients had operative times of 78 minutes compared to 111 minutes for CEA (p<.001).10 The SVS now recommends TCAR as superior or preferable to CEA in patients meeting CMS high-risk criteria.7

Conclusion

Carotid endarterectomy is the gold standard treatment for CAS. While well validated in the literature, this treatment approach is associated with higher rates of stroke and death in patients meeting CMS high-risk criteria. Utilization of TF-CAS has demonstrated poor outcomes compared to CEA limiting its acceptance. TCAR has shown effectiveness and outcomes comparable to CEA in stroke and death as well as lower myocardial infarction rates post operatively. While still early in its application, TCAR presents a minimally invasive treatment option for CAS that is beneficial to patients meeting CMS high-risk criteria. Continued research and completion of a randomized controlled trial would be beneficial for the continued evaluation of postoperative outcomes and long-term patency rates.

References

1. Mortality in the United States, 2020. National Center for Health Statistics. Accessed August 31, 2022. https://www.cdc.gov/nchs/data/databriefs/db427.pdf

2. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: A report from the American Heart Association. Circulation. 2022;145(8):e153-e639. doi:10.1161/CIR.0000000000001052

3. Chaturvedi S, Lalla R, Raghavan P. Trends and controversies in carotid artery stenosis treatment. F1000Res. 2020;9. doi:10.12688/F1000RESEARCH.25922.1/DOI

4. Rao V, Liang P, Swerdlow N, et al. Contemporary outcomes after carotid endarterectomy in high-risk anatomic and physiologic patients. J Vasc Surg. 2020;71(1):104-110. doi:10.1016/J.JVS.2019.05.041

5. Hicks CW, Nejim B, Locham S, Aridi HD, Schermerhorn ML, Malas MB. Association between Medicare high-risk criteria and outcomes after carotid revascularization procedures. J Vasc Surg. 2018;67(6):1752-1761.e2. doi:10.1016/J.JVS.2017.10.066

6. Song P, Fang Z, Wang H, et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob Health. 2020;8(5):e721-e729. doi:10.1016/S2214-109X(20)30117-0

7. AbuRahma AF, Avgerinos ED, Chang RW, et al. Society for Vascular Surgery clinical practice guidelines for management of extracranial cerebrovascular disease. J Vasc Surg. 2022;75(1):4S-22S. doi:10.1016/J.JVS.2021.04.073

8. Schermerhorn ML, Liang P, Eldrup-Jorgensen J, et al. Association of transcarotid artery revascularization vs transfemoral carotid artery stenting with stroke or death among pa tients with carotid artery stenosis. JAMA. 2019;322(23):2313-2322. doi:10.1001/

JAMA.2019.18441

9. Medicare National Coverage Determinations Manual Chapter 1, Part 1 (Sections 10-80.12). Centers for Medicare and Medicaid Services. Published September 8, 2021. Accessed August 7, 2022. https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Downloads/ ncd103c1_Part1.pdf

10. Schermerhorn ML, Liang P, Dakour-Aridi H, et al. In-hospital outcomes of transcarotid artery revascularization and carotid endarterectomy in the Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg. 2020;71(1):87-95. doi:10.1016/J.JVS.2018.11.029

11. Müller MD, Lyrer P, Brown MM, Bonati LH. Carotid artery stenting versus endarterectomy for treatment of carotid artery stenosis. Cochrane Database Syst Rev. 2020;2(2):CD000515. doi:10.1002/14651858.CD000515.PUB5

12. Paraskevas KI, Mikhailidis DP, Veith FJ. Mechanisms to explain the poor results of carotid artery stenting (CAS) in symptomatic patients to date and options to improve CAS outcomes. J Vasc Surg. 2010;52(5):1367-1375. doi:10.1016/J.JVS.2010.04.019 doi:10.7759/CUREUS.4935

13. Morr S, Vakharia K, Fanous AA, Waqas M, Siddiqui AH. Utility of intravascular ultrasound during carotid angioplasty and stenting with proximal protection. Cureus. 2019;11(6):e4935.

14. SVS VQI TransCarotid Revascularization Surveillance Project. ClinicalTrials.gov. Published March 4, 2021. Accessed August 15, 2022. https://clinicaltrials.gov/ct2/show/NCT02850588

15. Naazie IN, Cui CL, Osaghae I, Murad MH, Schermerhorn M, Malas MB. A systematic review and meta-analysis of transcarotid artery revascularization with dynamic flow reversal versus transfemoral carotid artery stenting and carotid endarterectomy. Ann Vasc Surg. 2020;69:426 -436. doi:10.1016/J.AVSG.2020.05.070

16. Galyfos GC, Tsoutsas I, Konstantopoulos T, et al. Early and late outcomes after transcarotid revascularisation for internal carotid artery stenosis: A systematic review and meta-analysis. Eur J Vasc Endovasc Surg. 2021;61(5):725-738. doi:10.1016/J.EJVS.2021.01.039

17. Gao J, Chen Z, Kou L, Zhang H, Yang Y. The efficacy of transcarotid artery revascularization with flow reversal system compared to carotid endarterectomy: A systematic review and metaanalysis. Front Cardiovasc Med. 2021;8:695295. doi:10.3389/FCVM.2021.695295