Study design and patients
This retrospective study included patients with NACAO who visited the Neuro-interventional Department of XXX Hospital from January 2017 to December 2020. The diagnosis was based on carotid ultrasound, magnetic resonance angiography (MRA), and/or computed tomography angiography (CTA), showing no blood flow through the occluded segment of the carotid artery. The inclusion criteria were 1) 18-75 years of age, 2) Carotid ultrasound, CTA, and/or MRA confirmed unilateral or bilateral CAO (no blood flow signal in the lumen), and 3) the occluded site included the common carotid artery (CCA) or internal carotid artery (ICA). The exclusion criteria were: 1) severe disability (modified Rankin Scale (mRS) >4), 2) accompanied by severe complications such as severe cardiopulmonary insufficiency or malignant tumor, 3) intracranial aneurysms or cerebral arteriovenous malformations, 4) peptic tract ulcer or other bleeding diseases, 5) contrast agent allergy or renal insufficiency that could not tolerate contrast, or 6) pregnancy or perinatal period. The procedures followed were in accordance with the “Declaration of Helsinki” and the ethical standards of the responsible committee on human experimentation (the Ethics Committee of our hospital). This study was approved by the Ethics Committee (SBNK-YJ-2021-005-01) of our hospital. The requirement for informed consent was waived by the committee.
Classification of carotid artery occlusion
Based on many years of clinical experience in NACAO endovascular recanalization and repeated and in-depth study of patients’ DSA image data, CAO is divided into the following four types according to the segment, length, and whether the proximal and distal lumens are developed. The ICA segmentation was based on the seven-segment method proposed by Bouthillier (C1, cervical; C2, petrous; C3, lacerum; C4, cavernous; C5, clinoidal; C6, ophthalmic; and C7, communicating) [17]. In type I, the occluded segment is located in the CCA or involves ≤2 consecutive segments in C1-C7. In type II, the occluded segment involves ≥3 consecutive internal carotid artery segments proximal to C5. In type III, the occluded segment involves ≥3 consecutive ICA segments, including C5. In type IV, the occluded proximal or distal lumen of the carotid artery is completely unrecognizable (Figure 1). [17] 17
Vascular recanalization therapy
Patients with CAO meeting the following indications and contraindications were suitable for endovascular recanalization. The indications were a) color Doppler ultrasound, CTA, and/or MRA showed occlusion of the CCA or ICA and was confirmed by cerebral angiography to have no forward blood flow at all, b) ischemic symptoms consistent with the occlusion side, and ischemic events still occurred under the conditions of anti-platelet aggregation, statins, and strict control of risk factors, c) computed tomographic perfusion (CTP) or perfusion-weighted imaging (PWI) confirmed that there was an obvious decrease in cerebral blood flow around the infarcted area within the CAO blood supply range, and d) the Alberta Stroke Program Early Computerized Tomography Score (ASPECT) score of the occluded side was ≥6 points [18]. The contraindications were a) asymptomatic or stable CAO after drug treatment, b) acute CAO within the time window of mechanical thrombectomy, c) CAO with anterior blood flow of grade 1, d) history of stent implantation in the CAO site, e) the proximal or distal lumen of CAO cannot be identified at all, i.e., type IV CAO, f) high-resolution magnetic resonance imaging showed obvious tortuosity of blood vessels in the occluded segment, or g) renal failure or severe allergy to contrast agents.
All patients underwent magnetic resonance imaging (MRI)/diffusion-weighted imaging (DWI), high-resolution MRI, PWI, or CTP, and digital subtraction angiography (DSA) before operation. Aspirin enteric-coated tablets (100 mg, once a day) and clopidogrel tablets (75 mg, once a day) were taken regularly for at least 5 days before the operation. The operation was performed by endotracheal intubation and general intravenous anesthesia (sufentanil, propofol, and rocuronium). Bilateral femoral arteries were punctured and placed with vascular sheaths, 8F on the right side and 4F on the left side. Whole-body heparinization (80 U/kg) was performed, and activated clotting time (ACT) was monitored. An 8F guide catheter (Mach1, Boston Scientific, Natick, MA, USA) was placed at the proximal end of the occlusion, and a proximal balloon occlusion catheter (Merci, Concentric Medical, Stryker Corp., Mountain View, CA, USA) was used if there was sufficient space at the proximal end. A 4F catheter (VER, Cordis Medical, Fremont, CA, USA) was placed in the contralateral ICA, vertebral artery, or ipsilateral external carotid artery to show occluded distal lumen (i.e., the collateral branch formed by the contralateral ICA, vertebral artery, or ipsilateral external carotid artery). Simultaneous double catheter angiography showed the proximal and distal lumen of the occluded segment and served as a road map to guide endovascular recanalization. A microcatheter (Excelsior SL-10, Stryker; Echelon-10, ev3 Endovascular Inc., Plymouth, MN, USA) combined with a microwire (PILOT 150, Abbott; PT2, Boston Scientific, Natick, MA, USA) was used to try to break through the proximal end of the occlusion. If it failed, a 4F contrast catheter (MP A1 125 cm, Cordis Medical, Fremont, CA, USA) combined with a super slippery guidewire (Terumo, Tokyo, Japan) was used to break through the proximal end of the occlusion. After the microguidewire and microcatheter passed through the occluded segment, the angiography confirmed that they were in the normal lumen, and then the exchange guidewire (Synchro, Stryker Corp., Kalamazoo, MI, USA) was placed in the distal normal lumen. If the occlusion’s distal end was located proximal to C2, a distal protection device (Spider FX, ev3 Endovascular Inc., Plymouth, MN, USA) was used. The proximal balloon occlusion catheter was filled to block the flow. A small balloon (Ryujin, Terumo, Tokyo, Japan) with a diameter of 2 mm was used to expand from far to near with a microguidewire as the track, and the lumen was judged by angiography. The sacculus expansion stent (Apollo, MicroPort Scientific Corp., Shanghai, China) with a 3-4 mm diameter was placed at sites with irregularities or obvious stenosis at the site distal to C1. The proximal part of C1 was reconstructed with a self-expanding stent (Wallstent, Boston Scientific, Natick, MA, USA). A sacculus (Ryujin, Terumo, Tokyo, Japan; Sterling, Boston Scientific, Natick, MA, USA) with a 2-5 mm diameter was used for posterior dilation when the residual stenosis was more than 30% confirmed by angiography. Finally, ipsilateral carotid angiography was performed to evaluate the anterior blood flow according to the thrombolysis in the cerebral infarction (TICI) grading system [19]. TICI 2b or 3 levels are defined as successful recanalization.
Postoperative care
ECG and blood pressure monitoring were carried out after the operation. The systolic blood pressure was strictly controlled to be lower than the baseline pressure by 10-20 mmHg within 24 days after the operation. Nicardipine was injected intravenously when blood pressure was high, and dopamine was injected intravenously when blood pressure was low due to carotid sinus reflex. Patients’ consciousness, speech, limb activities, and other neurological functional states were monitored. If there was any abnormality, carotid vascular ultrasound, brain CT, and/or magnetic resonance imaging were performed to timely find and address complications such as stent thrombosis, cerebral hemorrhage, and cerebral infarction.
Observation indicators
The differences in the success rate of endovascular recanalization, the incidence of re-occlusion, and the incidence of complications were observed among different types of patients. In addition, the long-term prognosis of the patients of different types was compared.
Follow-up
Clinical follow-up was performed routinely at 1, 3, 6, and 12 months after the operation. The mRS score and whether stroke or transient ischemic attack (TIA) occurred were followed once a year. Color Doppler ultrasound of cervical vessels was reexamined 1 week and 1 month after the operation. CTA or DSA was reexamined 3-12 months after the operation, and imaging reexamination was performed at any time if stroke or TIA occurred. Images showing stenosis of >50% of the lumen after recanalization were defined as restenosis, and no forward blood flow in the lumen was defined as re-occlusion.
Statistical analysis
SPSS 22.0 (IBM Corp, Armonk, NY, USA) was used to analyze the data. The Kolmogorov-Smirnov test was used to test whether the continuous data were normally distributed. Continuous data with a normal distribution are expressed as means ± standard deviations and were analyzed using the paired t-test (within-group comparisons) or ANOVA with Tukey’s post hoc test (multiple group comparison). Continuous data with a non-normal distribution are presented as medians (25th-75th quartiles) and were analyzed using the Wilcoxon symbolic rank test (within-group comparisons) or the Kruskal-Wallis test for multiple comparisons. The categorical data are expressed as n (%) and were analyzed using Fisher’s exact test. Two-sided P-values <0.05 were considered statistically significant.