Emergency carotid artery revascularization using Casper-RX stent: A single-center experience

Abstract

Background

Casper-RX (MicroVention, Aliso Viejo, California, USA) is a dual-layer closed cell stent recently introduced as a carotid artery revascularization device. Although its effectiveness and safety has been proved in elective cases, there are contradictive results regarding its patency in emergency settings. The purpose of the study is to present our single-center experience with the Casper-RX stent in the emergency interventions.

Patients and methods

Consecutive patients who underwent emergency carotid artery stenting using Casper-RX system with or without additional intracranial thrombectomy between August 2016 and June 2019 at our institution were included. Primary end point was the short-term patency of the carotid stents evaluated before hospital discharge by use of Doppler ultrasonography.

Results

Twenty-nine procedures performed on 28 patients were included in the study. All stents were patent on final angiograms. Acute stent occlusion was observed only in one case (3.4%) with a spontaneous cervical internal carotid artery dissection the day after the procedure. In 26 (89.6%) cases, an additional intracranial thrombectomy was performed with a successful recanalization rate of 96.1%. Seven adverse events occurred peri-/post-procedural: two cases (6.9%) with iatrogenic dissection of distal cervical internal carotid artery during intracranial thrombectomy, two parenchymal hematoma type 2 (6.8%), and three patients (10.3%) developed massive infarction.

Conclusion

This study supports the safety and efficacy of the Casper-RX stent in emergency endovascular carotid artery revascularization procedures.

Introduction

Mechanical thrombectomy (MT) in emergent occlusion of large cerebral arteries has proven to be effective.¹ In the HERMES collaboration, which consists of pooled patient data from five randomized trials, patients with intracranial large vessel occlusion presenting with a proximal severe stenosis or occlusion of the cervical internal carotid artery (cICA) make up 7.4% of all cases.¹ However, isolated acute symptomatic severe cICA stenosis or occlusion may also require emergent endovascular therapy. In both cases, angioplasty or stenting of the ipsilateral carotid stenosis or occlusion with or without intracranial MT is required to restore the cerebral perfusion.

Recently, a dual-layer closed cell stent, Casper-RX (MicroVention, Aliso Viejo, California, USA), with higher mesh density and smaller pore size compared with conventional single-layered stents was introduced. The idea was to reduce plaque protrusion, to provide better plaque coverage, and to decrease the risk of distal embolism.^2,3 In few studies, the effectiveness and safety of this newer stent in elective carotid artery stenting (CAS) procedures in symptomatic and asymptomatic patients has been proved.^3–6 However, the role of this stent or the dual-layer stents, in general, in the emergency setting still needs to be investigated. There are only few small case series presenting contradicting results regarding acute stent thrombosis and occlusion.^7–10 The only multi-center study is, however, retrospective, single-armed, and based on self-reporting.¹¹ The purpose of our study is to present our single-center experience with the Casper-RX stent in the emergency interventions.

Patients and methods

The research ethics committee approved the study, and the need for informed consent was waived.

We retrospectively searched in our database for consecutive patients who underwent emergency CAS using Casper-RX system between August 2016 and June 2019. Inclusion criteria were as follows:

• – Acute symptomatic intracranial large vessel occlusion of the anterior circulation and a tandem lesion (i.e. severe stenosis or occlusion of cICA) treated with intracranial MT and Casper-RX stent.

• – Severe stenosis or acute occlusion of the carotid bifurcation presenting with acute severe stroke due to hemodynamic disturbance treated with Casper-RX stents.

• – Patients having a Doppler follow-up evaluating stent patency before hospital discharge.

Severe cICA stenosis was defined as a ≥70% stenosis based on North American Symptomatic Carotid Endarterectomy Trial criteria.¹²

Data collection

For each case, following data were gathered: age, sex, length of hospital stay, National Institutes of Health Stroke Scale and modified Rankin Scale score on admission and right before hospital discharge, and presence and site of intracranial occlusion.

Procedural data

All procedures were performed on a dedicated biplane angiographic system (Siemens, Erlangen, Germany). All procedures were performed under general anesthesia using the standard femoral approach. Patients received an intravenous bolus of 5000 IU heparin after femoral puncture. Apart from heparin in the pressure bags for flushing (1000 IU/L), heparin therapy was not continued during or after the procedure. Nimodipine (2 mg) routinely was injected into the pressure bag connected to the guiding catheter to prevent catheter-induced vasospasm. An 8F sheath (Terumo, Tokyo, Japan) was inserted into the right common femoral artery. After navigating a 6F long sheath (Penumbra Neuron Max 088, Alameda, California, USA) into the relevant common carotid artery, the cICA distal to the occlusion or stenosis was catheterized by using a combination of an angioplasty balloon catheter (Trek 3/30; Abbott, Santa Clara, California, USA) and a 0.014-inch microguidewire. No embolic protection device was used. Following pre-dilation, a Casper-RX stent was deployed to cover the stenotic or occluded area. A post-dilation with a larger balloon catheter (Aviator Plus 6/30; Cordis, Fremont, California, USA) ensued. Following a control angiogram, depending on the intracranial arterial status, either a MT was performed or the procedure was ended. Patients were eligible for MT if they presented with acute occlusion of an intracranial large vessel, severe neurologic deficit, and salvageable neural tissue detected on computed tomography perfusion imaging. After the procedure, patients were routinely transported to the CT suite to have a non-contrast CT scan to exclude an immediate procedure-related complication. Following details regarding the procedures were recorded: post-interventional modified Treatment in Cerebral Infarction (mTICI) score, side and type of carotid pathology, number and size of the deployed stents, performing a pre- or post-stent balloon angioplasty, residual carotid stenosis, intra-procedural in-stent thrombus formation, and other stent-related complications. Successful recanalization was determined by distal intracranial flow and defined as a mTICI score of 2b or 3.

Peri-procedural management of anti-platelet medication

Data regarding administration of intravenous recombinant tissue-type plasminogen activator (rt-PA) prior to the procedure and peri-interventional management of anti-platelet medications were obtained.

In our institution, patients not taking any anti-platelet medication before admission receive 500 mg of intravenous acetylsalicylic acid (ASA) during the procedure. After exclusion of a significant intracranial hemorrhage or an extensive infarction on the control CT after 24 h of the procedure, the patient would be loaded with 375 mg clopidogrel. The double anti-platelet therapy (100 mg ASA and 75 mg clopidogrel daily) would continue for three months and then change to lifelong monotherapy with 100 mg ASA daily. In case of severe extracranial bleeding or necessary surgery (e.g. decompressive hemicraniectomy), second anti-platelet medication is withheld until the management of the bleeding or after the surgery. In case of necessary anti-coagulation, patients would be put on single anti-platelet medication.

Follow-up

Short-term imaging follow-up was mostly done with non-contrast CT depending on to the clinical status of the patient. Development of parenchymal hematoma type 2 (PH2) and massive infarction was recorded. The PH2, as described in the Heidelberg Bleeding Classification, is defined as hematoma occupying ≥30% of the infarcted tissue and exceeding the borders of ischemic lesion with obvious mass effect.¹³ Massive infarction was defined as infarction of the whole middle cerebral artery (MCA) or ICA territory.

Post-interventional evaluation of stent patency was performed with Doppler ultrasonography usually the day after the endovascular therapy. In case of neurological worsening, Doppler would be repeated. Acute stent occlusions were defined as occlusions occurred during the hospital stay.

Results

Demographic and clinical data

Between August 2016 and May 2019, 34 carotid arteries in 33 patients were stented in emergency settings using the Casper-RX system. Five cases had no Doppler follow-up during their hospital stay and were excluded from the study. One of the five cases simultaneously developed an acute myocardial infarction, was transported to the cardiology unit after the neurovascular procedure, and lost to follow-up. Two cases developed PH2 in the first 24 h following the intervention. One case had an iatrogenic perforation of the MCA during superselective catheterization and developed severe subarachnoid hemorrhage. One case presented with an already large infarct core on admission despite still being in the therapeutic time window and developed malignant infarction in the whole anterior cerebral artery and MCA territories despite MT. In those four patients, stent patency was not relevant and no Doppler follow-up was performed.

A total number of 29 procedures done in 28 patients were included in the study. One patient had acute occlusion of each ICA on consecutive days. Table 1 and Supplementary Table outline the demographic and clinical data.

Table 1.

Clinical and demographic data.

	All cases (n = 29)
Mean age in years (range)	71.7 (52–86)
Female	6 (21.4%)
Median length of hospital stay in days (range)	13 (1–60)
Median initial NIHSS scorea (range)	12 (1–24)
Median NIHSS at dischargeb (range)	4.5 (0–42)
mRS before treatmentb (range)	4.5 (0–5)
mRS at discharge (range)	2.5 (0–6)

^aAvailable only for 21/29 cases.

^bAvailable only for 20/29 cases.

mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale.

Procedural data

Data from the procedures can be found in Table 2 and Supplementary Table. All stents were patent on final angiograms. No significant residual carotid stenosis was noted. Incomplete wall apposition of the stents was not observed. In two cases, iatrogenic dissection of the distal cICA occurred during MT after stent implantation. Dissections were not hemodynamically significant and managed medically.

Table 2.

Data regarding the stenting and mechanical thrombectomy.

	All cases (n = 29)
Right-sided pathology	14 (48.2%)
Atherosclerotic cICA occlusion	23 (79.3%)
Severe cICA stenosis	4 (13.8%)
Spontaneous cICA dissection	2 (6.8%)
Pre-stent balloon-dilation	28 (96.5%)
Post-stent balloon-dilation	29 (100%)
Deployment of >1 stent in one ICA	6 (20.6%)
Intracranial thrombectomy	26 (89.6%)
Carotid T	10 (38.4%)
M1-MCA	10 (38.4%)
M2-MCA	5 (19.2%)
A2-ACA and M2-MCA	1 (4%)
Final mTICI score 2b/3	25 (96.1%)
Final mTICI score 3	21 (80.7%)
Iatrogenic dissection of distal cICA	2 (6.9%)
Sizes of stents (n = 35)
Casper-RX 10/30 mm	30 (85.7%)
Casper-RX 10/20 mm	5 (14.3%)

cICA: cervical internal carotid artery; MCA: middle cerebral artery; ACA: anterior cerebral artery; mTICI: modified Treatment in Cerebral Infarction.

Peri-interventional management of anti-aggregation and anti-coagulation

Peri-procedural management of anti-platelets and anti-coagulants are depicted on Table 3. One patient with atherosclerotic ICA occlusions on consecutive days at alternating sites was allergic to ASA. During the first intervention, he received only a heparin bolus without prior rt-PA and on the next day, he was loaded with 375 mg clopidogrel and the opposite cICA got occluded. After the second intervention, he continued to take 75 mg clopidogrel daily and showed no acute stent occlusion.

Table 3.

Peri-interventional management of anti-aggregation and anti-coagulation.

	All cases (n = 29)
Intravenous rt-PA	16 (55.1%)
Stenting with heparin only	1 (3.4%)
Stenting with heparin and ASA	23 (79.3%)
ASA administered during stenting	16 (55.2%)
ASA taken prior to hospital admission	7 (24.1%)
Stenting with ASA, clopidogrel and heparin	1 (3.4%)
Stenting with clopidogrel and heparin	1 (3.4%)
Stenting wit prior anti-coagulant, ASA and heparin	3 (10.3%)

rt-PA: recombinant tissue-type plasminogen activator; ASA: acetylsalicylic acid.

Follow-up

All patients received Doppler sonography during the hospital stay. Follow-up data are represented on Table 4 and Supplementary Table. Acute stent occlusion was observed only in one (3.4%) case. This was a 70-year-old male presenting with intra- and extracranial tandem occlusion of the ICA due to a spontaneous dissection. Because of unknown onset, the patient was not eligible for an intravenous thrombolytic therapy. During the intervention, the patient received intravenous 500 mg ASA and 5000 IU heparin. The occluded segment began distal to a kinking of the cICA and ended at the skull base. Dissected segment could be passed with a combination of the guiding catheter, microcatheter, and microguidewire. Following a successful intracranial MT for a carotid T occlusion, without pre-dilation, two Casper-RX stents (10 mm wide and 20 and 30 mm long, respectively) were deployed between the skull base and the common carotid artery and the artery got straightened. Post-dilation was performed to enhance the wall apposition. Control angiogram showed no evidence of stent thrombosis but remaining vessel wall irregularities at the distal end of the stent not requiring further treatment. The Doppler follow-up on the next day, however, showed occlusion of the stent and a CT angiography (CTA) confirmed the occlusion (Figure 1). The patient remained asymptomatic, thus the re-occlusion left untreated.

Table 4.

Follow-up and complications.

	All cases (n = 29)
Doppler follow-up during the hospital stay	29 (100%)
Acute stent occlusion	1 (3.4%)
In-stent thrombus formation	0 (0%)
PH2	2 (6.8%)
Massive infarction	3 (10.3%)

PH2: parenchymal hematoma type 2.

Figure 1.

(a) Initial lateral angiogram demonstrates abrupt change of vessel caliber, irregular luminal narrowing (arrowhead), and occlusion of cervical internal carotid artery due to a spontaneous dissection. Note the vessel kinking proximal to the occlusion. Non-subtracted angiogram on oblique anterior–posterior (b) and lateral (c) view show two tandemly placed Casper RX stents (10/20 mm and 10/30 mm). Adequate opening of the stents after balloon angioplasty with minimal residual stenosis (black arrows). On corresponding subtracted images (d and e), straightening of the vessel, reconstitution of the lumen, and remaining wall irregularities at the distal part of the stent (white arrows). (f) Curved computed tomography angiography reconstruction image verifying acute stent occlusion which was first detected on routine Doppler sonography made after 24 h after the procedure.

Two patients developed PH2. Three patients had poor intracranial collaterals and low Alberta Stroke Programme Early CT score on the initial CT and CTA, so they did not profit from the reperfusion and developed massive infarction. In those patients, repeat Doppler showed no stent occlusion or in-stent thrombus formation.

Discussion

To our knowledge, this is the largest single-center case series in the literature regarding the use of dual-layer stents in emergency settings with complete short-term imaging follow-up. In our series of 29 emergency cases treated with Casper-RX stent, we saw only one acute stent occlusion (3.4%). Among the reports from single-center case series in the literature, acute occlusion rates of Casper-RX stents after emergent endovascular ICA revascularization varies between 8% and 45%.^7–10 Rate of acute thrombus formation has been reported as high as 52.4%.⁸ Yilmaz et al., reporting 45% of acute stent occlusion in their series with 20 cases, concluded that this high rate might be attributable to insufficient peri-procedural platelet inhibition in the emergency setting.⁷ In the only multi-center retrospective study, Pfaff et al. found a lower acute occlusion rate of 7.5% and acute non-occlusive thrombosis rate of 13.1%. They, however, observed no statistically significant difference between patients with and without thrombus formation regarding the peri-procedural anti-aggregation and anti-coagulation regimens which differed widely among the institutions. So they hypothesized that higher rate of acute stent occlusion reported before might potentially be related to other factors (e.g., blood velocity profile, vascular tortuosity, coagulation parameters, and residual stenosis after stenting).¹¹

We support the hypothesis of Pfaff et al. because our only case with acute stent occlusion had a complex anatomy and pathology such as a proximal kinking and a distal occlusion due to dissection. The only reasonable explanation we could come up with for acute stent occlusion was that the dissection probably extended to the petrous segment of the ICA and the stent distally ended within the dissection rather than covering the whole pathologic segment and causing suboptimal stent opening (Figure 1). Although the lumen showed a normal calibre after post-dilation, this probably left a potential thrombogenic zone behind.

Another supporting data for this hypothesis would be that in our study group, we even had a patient with known ASA allergy presenting with a tandem occlusion, and the procedure was performed only with heparin without prior intravenous thrombolysis. He then was loaded with clopidogrel on the next day and the stent remained patent.

One difference of our practice is that we always use the stents with the largest calibre (10 mm wide) irrespective of the vessel diameter and perform always a post-stent angioplasty. We find the over-expansion of large-calibre stents helpful because of impaired evaluation of the extension of the stenotic segment when dealing with the proximal occlusion first. We routinely dilate the stent with a balloon catheter at the level of stenosis or at multiple levels if necessary and try to leave no stenosis behind.

One more difference of our practice could be the standard injection of nimodipine into the pressure bag of guiding catheter to prevent vasospasm. Although 2 mg of nimodipine is a small amount considering the dilution in a 1000 ml isotonic NaCl solution, these procedures take usually longer than a simple MT, and sufficient nimodipine could enter the bloodstream during the whole procedure. According to our experience, the use of prophylactic nimodipine is especially helpful when managing severely tortuous or kinked vessels. It might support the wall apposition along the distal part of the stent, thus preventing thrombus formation. None of the authors in the literature has mentioned the role of prevention or treatment of material-induced vasospasm during these procedures before.

We are not sure if the differences alone could explain our low acute occlusion rate compared to the literature. Yilmaz et al. observed the trend for smaller stent diameters in patients with acute stent occlusions but they concluded that it was insignificant.⁷

In our series, Doppler follow-up was usually done on the next day after the procedure and would not be repeated unless the neurologic condition of the patient deteriorated. There might be a chance of missing asymptomatic stent occlusions or in-stent thrombus formations after the next day of the treatment and unfortunately, we are not aware of long-term follow-up of those patients after discharge from our institution. In our series, however, in three patients only on ASA due to progressive infarction despite MT and stenting, repeat Doppler examination showed maintained patency of the stent. Since this is the most common practice regarding follow-up of patients during the hospital stay described in the literature, this point applies to each study.

Another limitation of this study and probably of others in the literature is the unknown response status of the patients to ASA and clopidogrel. It might be interesting to investigate this possible relationship.

Other limitations of the study include its retrospective nature, lack of a control group such as patients treated with other stents and small patient number.

Conclusion

Despite conflicting data in the literature, we believe that the dual-layer Casper-RX stent is safe and feasible in emergency endovascular carotid artery revascularization procedures. We think that stent over-sizing, sufficient post-dilation, and selective intra-arterial injection of nimodipine may positively affect the short-term stent patency along with proper platelet inhibition.

Author contributions

YO and MB contributed to the conception and design of the work, analysis and interpretation of the data, and drafting the paper. CC, BLS, and GFH contributed to acquisition of the data and critical revision. JR contributed to critical revision.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval statement/IRB approval number

The authors hereby state that this research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The local research ethics committee of Ulm University approved the study (160/19), and the need for informed consent was waived after anonymization of the data because of its retrospective and descriptive nature.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Yigit Ozpeynirci https://orcid.org/0000-0002-1261-7396