Journal of Vascular and Endovascular Therapy

Keywords

Carotid endarterectomy; Carotid Artery Stenting (CAS); Embolization; Thrombectomy; Ischemic stroke

Introduction

Stroke is the leading cause of long-term impairment and is highly attributable to modifiable vascular risk factors including atherosclerotic carotid artery stenosis. Plaque rupture and thromboembolism in these patients account for 15% of ischemic strokes [1]. Emboli originating from stenosed proximal carotid arteries can travel and cause intracranial Large Vessel Occlusions (LVOs) with devastating neurological deficits if intervention is delayed [2]. Early and aggressive recanalization of occluded cerebral vessels can be performed with stent retrievers and/or aspiration catheters but the decision to perform a concurrent carotid artery stenting with thrombectomy remains unclear. The timeline of both procedures is controversial and depends on severity of stroke, severity of carotid stenosis, presence of contralateral carotid stenosis, bleeding risk, and interventionalist discretion. A major consideration is initiation of antithrombotic medication after stenting and needs to be weighed against the risks of hemorrhagic conversion after stroke.

Carotid revascularization procedures such as Carotid Endarterectomy (CEA) or Transfemoral Carotid Artery Stenting (TF-CAS) are often used to reduce recurrent strokes in patients with symptomatic carotid stenosis alone [3]. CEA can be performed under general or local anesthesia and involves a surgical cut down on the common or internal carotid artery to remove plaque and emboli to reestablish cerebral blood flow [4]. The major complications of CEA include Myocardial Infarction (MI), perioperative stroke, and cranial nerve palsy [5]. TF-CAS is an alternative approach to carotid revascularization and is often preferable in high risk patients to reduce the aforementioned risks and complications associated with surgical neck exploration [6]. However, previous studies continue to show a higher rate of perioperative stroke in TF-CAS compared to CEA. This increased risk has been associated with unprotected aortic arch catheterization, suboptimal embolic protection, and carotid lesion crossing during embolic protection device placement.

Transcarotid Artery Revascularization (TCAR) is an alternative approach to standard carotid interventions and uses direct surgical access to the common carotid artery. TCAR minimizes embolic stroke using the ENROUTE transcarotid neuro protection system with cerebral blood flow reversal [7]. Previous studies have indicated the effectiveness of TCAR with a significantly low procedural stroke rate in high risk patients for CEA. Kwolek, et al. reported a 30 days stroke rate of 1.4% in patients undergoing TCAR compared to a 30 days stroke rate of 2.3% and 4.1% in CEA and TF-CAS, respectively [8]. Upon literature review, there remains minimal evaluation of outcomes of TCAR procedure following Mechanical Thrombectomy (MT) for acute ischemic stroke patients with symptomatic carotid stenosis.

This paper studies a series of acute stroke patients with extracranial carotid lesions who underwent TCAR under planned conscious sedation supplemented with local anesthesia following MT to evaluate primary survival outcomes, complication rates, and long-term clinical outcomes.

Materials and Methods

This paper describes a retrospective, single-center case series study of patients at the university of Maryland medical center who underwent MT for acute ischemic stroke followed by TCAR in the same hospitalization. Patient data was extracted from Epic, the electronic health records system, using TCAR codes. All research methods were conducted in accordance with Good Clinical Practice (GCP) guidelines and IRB (Institutional Review Board) was obtained. Patient-informed consent was waived by the IRB.

Data from adult patients who underwent TCAR between December 2018 and October 2021 were reviewed. The inclusion criteria were defined as patients with concomitant intracranial vessel occlusion and significant carotid artery stenosis who received MT for an acute stroke prior to carotid revascularization in the same hospitalization. Relevant patient demographics, medical and surgical history, comorbidities, and medication history were obtained from patients’ charts. The preoperative covariates analyzed included hypertension, diabetes mellitus, smoking history, history of Transient Ischemic Attack (TIA) or stroke, and history of anticoagulation.

Upon admission, non-contrast Computed Tomography (CT) scan, CT angiography, CT perfusion scan, and/or Magnetic Resonance (MR) imaging/MR angiography was performed to determine severity and location of ischemia and thrombosis, rule out intracranial hemorrhage, and guide MT. Patients presenting within 4.5 hours of symptom onset without clear contraindication to systemic thrombolysis were treated with tissue Plasminogen Activator (tPA, 0.9 mg/kg) before transfer for thrombectomy. Exclusion criteria for MT at our institution generally include:

• Mild stroke symptoms defined as an admission National Institutes of Health Stroke Scale (NIHSS) score <6.

• The presence of a large completed territorial infarction by non-contrast CT, defined as an Alberta stroke program early CT score <6 or by Magnetic Resonance Imaging (MRI), defined as an infarction volume of >90 mL of brain.

• Pre-stroke modified Rankin Score (mRS) of >3.

• Target territory intracranial hemorrhage.

Intracranial mechanical thrombectomy procedure

All patients underwent standard surgical access to the femoral artery under fluoroscopic guidance following local anesthetic with lidocaine. Long sheaths of 80 cm or greater in length were used for arterial catheterization. If applicable and feasible, balloon angioplasty was performed in the stenosed internal carotid artery to improve flow to distal vessels. Angiography was then performed to visualize thrombus in the affected cerebral artery segments followed by deployment of a stent retriever using roadmap technique. After waiting several minutes to allow for clot integration into the stent retriever, the device was removed while aspiration was applied via the distal access catheter.

A final post-intervention angiography was acquired at the completion of the procedure. Success of intracranial vessel recanalization was graded according to the Thrombolysis in Cerebral Infarction (TICI) score. A TICI score of 2b (greater than 50% territory reperfusion), 2c (near complete reperfusion), or 3 (complete reperfusion) is considered successful reperfusion [9].

Further studies, including vascular duplex ultrasound and MRI, were obtained post-thrombectomy to characterize carotid anatomy and select patients as candidates for TCAR. Indications for TCAR under local anesthesia included patients with high carotid bifurcations, poor general anesthesia candidates, high risk for stroke due to unstable plaque, and those with multiple comorbidities.

TCAR surgical procedure

All patients underwent standard surgical access to the common carotid artery just above the clavicle under local anesthesia, such as lidocaine or bupivacaine, or general anesthesia. A transverse incision was made between the sternal and clavicular heads of the sternocleidomastoid muscle followed by longitudinal division of the carotid sheath. A polypropylene suture was pre-placed in the anterior wall of the Common Carotid Artery (CCA) to facilitate hemostasis upon removal of the arterial sheath at completion of the procedure. A micropuncture needle was inserted into the artery and advanced into the CCA followed by exchange for a microsheath. Angiogram was then performed to isolate the location of lesion before introduction of the SilkRoad ENROUTE transcarotid stent system. Once femoral access was obtained, flow reversal catheters were connected and a wire was advanced into the sheath through the lesion, and finally into the distal Internal Carotid Artery (ICA). The lesion was pre-dilated to the normal size of the ICA with balloon angioplasty under fluoroscopy; a bare metal, self-expanding stent was deployed based upon the CCA diameter and oversized appropriately. All patients received weight based intra-operative heparin dosing with the goal ACT (activated clotting time) of 250 seconds or greater. For site hemostasis, patients were administered protamine, Gelfoam, and/or Tisseel. Patients were either initiated or continued on daily aspirin and clopidogrel post-procedure for 90 days before re-evaluation of regimen. Neurological examinations were conducted prior to TCAR, immediately post-operatively, and at specified intervals onwards. A post-stenting angiogram was performed to confirm patent CCA and ICA as well as antegrade flow into the brain.

Clinical follow-up

After carotid revascularization, all patients were monitored with hourly neurovascular checks and strict blood pressure guidelines to minimize reperfusion related intracranial hemorrhage. All patients were continued on a regimen of aspirin, statin, and anti-platelet therapy to reduce risk of recurrent stroke. Post-operative protocol included follow-up carotid duplex imaging to assess patency of carotid stent and physical exams at 1 month, 3 months, 6 months, and 12 months intervals. A full history and physical examination to assess neurological status was performed at every visit by both the vascular surgery team and neurology team. The degree of disability in patients was measured by mRS as well as the NIHSS.

Results

Patient characteristics

Five patients who underwent a post-thrombectomy TCAR were identified from a systematic chart review. Three patients were female with a median age of 66 and an Interquartile Range (IQR) of 15 (Table 1). All patients reported a history of hypertension; two patients reported prior tobacco use, four patients had a history of diabetes mellitus, and no patients reported having prior Transient Ischemic Attack (TIA) or stroke events. One patient was found to be a rapid CYP2C19 metabolizer while another patient was an intermediate CYP2C19 metabolizer con irmed by genetic testing. All patients presented with acute onset neurological de icits as graded by the NIHSS, with a range from 18 to 28. Three patients were appropriate candidates for thrombolytic therapy based on time of presentation and medication history.

Table 1: Demographic characteristics and comorbidities of patients undergoing Transcarotid Arterial Revascularization (TCAR) following Mechanical Thrombectomy (MT).

Lesion characteristics

Four patients had left sided occlusion on CTA and one patient had a right sided occlusion. The Middle Cerebral Artery (MCA) was found to be occluded in all subjects, with localization to the M1 segment in 80% of subjects. Three patients were found to have Internal Carotid Artery (ICA) occlusion in addition to the MCA (Table 2). Establishment of TICI 2A, 2B, 2C, or 3 flows was successful in all five patients. More specifically, TICI 2A was seen in one patient, TICI 2C was seen in 3 patients, and TICI 3 was seen in one patient.

Table 2: Demographic characteristics and comorbidities of patients undergoing Transcarotid Arterial Revascularization (TCAR) following Mechanical Thrombectomy (MT).

TCAR was recommended in patients with continued high stroke risk after thrombectomy based on carotid anatomy, high risk plaques defined as focal mural thrombi or long lesions (>15 mm), neurological symptoms, high percentage of stenosis, and/or occlusion of contralateral vessels. All five patients were classified as high risk for repeat stroke with four of five patients at extreme risk due to multiple comorbidities, genetic factors, and anatomy. Two patients had greater than 80% stenosis of the ipsilateral carotid artery. Three patients had a high carotid bifurcation on imaging and two patients had long plaques extending high into the neck both indications for a TCAR approach at our institution. Four of five patients had a MT-TCAR interval between 3 to 8 days; however, one patient underwent TCAR 246 days after their thrombectomy due to disease complications and hospitalization course (Table 3).

Table 3: Postoperative outcomes of Transcarotid Arterial Revascularization (TCAR).

Four of five patients were initiated on antiplatelet therapy (clopidogrel) prior to their TCAR procedure due to low risk of conversion. Both patients who were found to be rapid or intermediate CYP2C19 metabolizers were initiated on clopidogrel 75 mg and 150 mg, respectively, in response to their metabolization studies. Aspirin was initiated 24 h after TPA administration for patients previously on the medication.

Transcarotid artery revascularization characteristics

Two patients were administered general anesthesia at the beginning of their TCAR procedure while three patients were given local anesthesia with conscious sedation. One patient required a hybrid procedure due to a dissection of the left CCA and difficult anatomy. General anesthesia was given intraoperatively prior to cutdown. The CCA was divided to safely enter the true lumen, and under direct visualization, an 8 French Silk Road sheath was advanced into the common carotid followed by three self-expandable stents from the distal internal carotid artery extending to the mid-internal carotid artery and finally to the bifurcation. Angiography was performed to confirm normal cerebral perfusion and hemostasis was achieved. One patient was administered protamine (100 mg), Gelfoam, and Tisseel at the end of their operation, three patients were only given Gelfoam and Tisseel, and the patient who required a cutdown was left with a Provena in place.

No major adverse cardiac events, cranial nerve injury, stroke events, stent malfunction, stent restenosis, or site hematomas were reported for all patients during their hospitalization. One patient was found to have subcutaneous emphysema and mild pneumomediastinum in the first two days post-operatively that resolved before discharge. Another patient experienced orthostatic hypotension and autonomic dysregulation requiring midodrine for the first two days post-operatively that resolved prior to discharge as well. The median length of hospital stay post-TCAR was 6 days with a range of 3 to 12 days.

Clinical outcomes

All patients showed patent carotid stents on post-operative duplex with neurologic exams that were either improved from initial presentation or harde turned to baseline. Based on neurologic exams of the most recent clinic visit, the median NIHSS score was calculated to be 2 with a range from 0 to 7 an improvement from a median presentation score of 20. The median mRS was 2 with a range from 0 to 4.

DISCUSSION

In the current series, we report on stroke treatment in the setting of tandem intracranial vessel occlusion and extracranial carotid artery occlusion. 15%-20% of patients presenting with intracranial vessel occlusion have concurrent high grade ICA stenosis or complete occlusion [10]. Even with systemic thrombolysis, these patients have lower recanalization rates and poorer clinical outcomes. The most commonly used procedures in current practice consist of acute stent placement in the carotid lesion or thrombectomy alone without definitive revascularization of the carotid artery [11]. Treatment decisions are often complex and involve multiple factors including size of parenchymal stroke burden. There are additional clinical, anatomic, and technical considerations involved and randomized trials comparing these approaches are currently lacking.

Neuro-interventionalists can perform concurrent carotid artery stent placement after intracranial thrombectomy [12]. However, the optimal management strategy for carotid lesions during endovascular thrombectomy remains controversial. Routine stenting of an occluded cervical carotid artery is not always performed immediately before or after intervening on the distal intracranial occlusion due to risk of intracranial hemorrhage from initiation of antiplatelet medications. Post-operative management requires maintenance of carotid artery patency, and single or dual antiplatelet regimens are routinely administered for carotid artery stent placements. However, this increases the risk of hemorrhagic conversion and requires careful risk-benefit analysis before initiating [13]. Heck, et al. observed a 22% incidence of symptomatic Intracranial Hemorrhage (sICH) after initiating abciximab in patients with primary stenting of the extracranial carotid artery followed by intracranial mechanical thrombectomy. In another study, Sojka et al. reported sICH in 11.8% of patients and one of 34 patients developed stent re-occlusion [14].

TCAR after mechanical thrombectomy for acute ischemic stroke was shown to be safe and effective in our small case series of patients with tandem intracranial and extracranial occlusions. The preliminary results, defined by clinical follow-up at 1 month, 3 months, 6 months, and 12 months showed improvement or resolution of presentation symptoms and no further complications such as stroke or decline in neurological function. According to the SWIFT study, all five patients met criteria for a good neurologic outcome based on their mRS. 80% of patients improved >10 NIHSS points, with an average improvement of 18 points [15,16]. This study also supports the efficacy of the procedure, with 6 months and 12 months occlusion rates of 0% and no patients requiring restenting at 12 months.

Conclusion

Carotid endarterectomy was established as the treatment of choice for moderate to severe symptomatic carotid artery stenosis through the NASCET and ECSCT trials, specifically as a method of preventing secondary stroke. While CEA remains a first-line treatment for carotid artery stenosis, there is significant data supporting TCAR as an equivalent approach in outcomes, efficacy, and cost. TCAR procedures have similar outcomes relative to CEA with respect to 30 days and 1 year rates of stroke and death and is a well-tolerated procedure by older patients at high surgical or anatomic risk for CEA. It is a less invasive option with the lowest reported overall stroke rate of all prospective trials of carotid artery stenting.

Limitations

This study is not a randomized trial and therefore safety and efficacy cannot be directly compared to a control group. It also faces the inherent disadvantages of being a retrospective study and is prone to selection bias, recall bias, and misclassification bias. Further validation of these results requires a randomized, prospective trial with a larger cohort of patients.

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