Ischemic stroke
ORIGINAL RESEARCH
Stenting of symptomatic intracranial stenosis using balloon mounted coronary stents: a single center experience Christopher R Durst,1 Scott R Geraghty,2 Andrew M Southerland,3 Robert M Starke,4 Karen Rembold,5 Shaneela Malik,6 Max Wintermark,1 Kenneth C Liu,4 R Webster Crowley,4 John Gaughen,1 Mary E Jensen,1 Avery J Evans1 1
Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia, USA 2 Advocate Neurovascular Center, Chicagoland, Illinois, USA 3 Department of Neurology, University of Virginia Health System, Charlottesville, Virginia, USA 4 Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia, USA 5 Department of Neurology, Tufts Medical Center, Boston, Massachusetts, USA 6 Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA Correspondence to Dr C R Durst, University of Virginia Health Systems, Department of Radiology and Medical Imaging, PO Box 800170, Charlottesville, VA 22908, USA; [email protected] CRD and SRG contributed equally. Received 21 February 2014 Accepted 3 March 2014
ABSTRACT Objective Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks. Intracranial stenting with off-label balloon mounted coronary stents (BMCS) may be a viable alternative for patients with symptomatic intracranial stenosis who fail best medical therapy. Design Between December 2005 and June 2012, 42 symptomatic intracranial stenoses were treated with a BMCS after failing medical management. Procedural records, clinical outcomes, and imaging follow-up were reviewed. Outcome measurements included technical success rate, morbidity and mortality, long term stent patency, and clinical outcomes, as measured by the modified Rankin Scale. Results The technical success rate was 98% (41 of 42 lesions). Morbidity within the first 30 days was 7.1% (three of 42 lesions). Overall morbidity, including both periprocedural and long term evaluation, was 9.5% (four of 42 lesions). There were no deaths. Follow-up imaging was available for 30 stents (71%) with an average follow-up time of 35.1 months. Restenosis (>50%) and retreatment were observed in 20% and 10% of cases, respectively. Clinical evaluation by a neurologist ≥30 days postprocedure was available in 40 of 42 cases (95%) with an average of 32.1 months. At presentation, 55% of patients had a modified Rankin Scale (mRS) score of ≤2. At follow-up, 74% of patients were found to have an mRS score of ≤2. Conclusions This study suggests that BMCS may benefit patients with symptomatic intracranial stenosis who experience stroke or transient ischemic attack in spite of best medical therapy.
risk.2 The Wingspan system is criticized for being bulky and requiring a multi-step deployment.5 6 In contrast, balloon mounted coronary stents (BMCS) can be deployed in a single step, eliminating the number of exchanges required for deployment of a Wingspan stent. We hypothesize that intracranial stenting with off-label BMCS would be an uncomplicated, clinically viable alternative for patients with symptomatic ICS who fail best medical therapy.
PATIENTS AND METHODS Study design This study was performed under the auspices of our institutional review board. At our institution, all patients who present with an ICS (defined as >70% stenosis) are treated with aggressive medical management, based on the results of the WASID (Warfarin–Aspirin Symptomatic Intracranial Disease) and SAMMPRIS trials as a guideline.1 2 Patients are only considered for intracranial stenting after they have failed best medical management, defined as recurrent ischemic symptoms localizing to the stenotic arterial territory. A retrospective chart review identified 39 patients with 42 symptomatic lesions, despite best medical management, who subsequently underwent attempted BMCS placement between December 2005 and June 2012. All clinical and imaging outcomes were independently adjudicated by vascular neurologists and diagnostic neuroradiologists, respectively, unaffiliated with the procedure.
Procedural technique OBJECTIVE
To cite: Durst CR, Geraghty SR, Southerland AM, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011185
Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks, resulting in significant morbidity and mortality.1 Even with best medical therapy, the risk of recurrent stroke remains high.2–4 The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial demonstrated that intracranial stenting for symptomatic intracranial stenosis (ICS) (70–99%) with the Wingspan stent system (Stryker Neurovascular, Fremont, California, USA) is significantly more dangerous than best medical management, primarily driven by periprocedural stroke
Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Written informed consent was obtained for all procedures. All patients were placed on dual antiplatelet therapy (aspirin 325 mg and clopidogrel 75 mg) prior to stenting. For patients on clopidogrel, preprocedure platelet reactivity assay was checked using the VerifyNow P2Y12 test (Accumetrics, San Diego, California, USA). If subtherapeutic, patients were given a clopidogrel ‘load’ (300 or 600 mg) and rechecked. If they remained subtherapeutic, patients were prescribed thienopyridine and rescheduled for a later procedure. Patients were to continue taking aspirin for life and clopidogrel (or, alternatively, thienopyridine in clopidogrel nonresponders) for 90 days following stent placement. 1
Ischemic stroke All procedures were performed under general anesthesia. Access was obtained in a standard fashion. Intravenous heparin was administered during the procedure to achieve an activated coagulation time of between 250 and 300 s. A BMCS (Multi-Link Vision cobalt–chromium coronary stent; Abbott Vascular, Abbott Laboratories, Abbott Park, Illinois, USA) was advanced over a microguidewire across the intracranial stenosis using roadmap guidance. Digital subtraction angiography (DSA) was performed through the guide catheter prior to stent deployment to confirm appropriate stent positioning. The stent was then slowly deployed over several minutes using intermittent fluoroscopy, inflating approximately 1 atm every 30–60 s initially. After reaching the desired inflation, the balloon was deflated and removed, leaving the stent in place. Immediate post-stenting DSA was performed, as well as post 10 and 20 min DSA to ensure there was no thrombus formation in the stent or distal thromboembolism. Heparin anticoagulation was not reversed following the procedure. Patients were observed in a neurocritical care unit for 24 h postprocedure to monitor neurological examination and new events, and ensure hemostasis at the femoral site.
RESULTS Patient demographics and lesion characteristics
Procedural outcomes
Endovascular related complications
In all cases, pretreatment and immediate post-treatment ICS was measured by DSA using standard measurement methods.7 Treatment studies were evaluated for complications related to stent deployment, including failed deployment, inappropriate positioning of the stent, vessel injury, or thromboembolic events. At discharge, patients were scheduled for a 3–6 month angiographic follow-up with intent to image via CT angiography, MR angiography, or additional angiographic studies at 12 and 24 months. Follow-up imaging was evaluated for stent patency, recurrent stenosis, and stent related vascular complications. A recurrent stenosis was defined as stenosis greater than 50% compared with the angiography images acquired at the end of the procedural study.
Overall treatment related morbidity, including periprocedural and late events, was 9.5% (four patients). Mortality was 0%. Each of the morbid events involved a clinical stroke with diffusion weighted imaging correlate involving the treated vascular territory. A univariate analysis did not identify any of the patient demographics or lesion characteristics as predictors of outcome. A risk analysis (figure 1) identified the posterior circulation as experiencing more complications at an earlier time point, although this did not reach statistical significance ( p=0.124).
Between December 2005 and June 2012, BMCS was attempted in 39 patients with 42 symptomatic intracranial stenoses. Three patients had more than one stenosis that required treatment. In one patient, the lesions were in tandem within one vascular territory. In the other two patients, the lesions were in opposite hemispheres. Twenty-two lesions were in the posterior circulation and 20 in the anterior circulation. Mean age was 60 years, with 38% women (table 1).
Technical success A total of 41 stents were successfully placed across 42 lesions for a technical success rate of 98% (table 2). In one case the BMCS could not be advanced beyond a tortuous siphon to stent a distal right internal carotid artery stenosis. This lesion was instead treated with balloon angioplasty only. One stenosis required pre-dilation with balloon angioplasty. The remainder of the cases were performed without pre-dilation. Post-dilation was not required in any case. In one case of basilar artery stenosis, the BMCS was deployed inside a stenotic Wingspan stent.
Table 1
Patient demographics and lesion characteristics
Characteristic
Clinical assessment Through a thorough review of the medical records, the clinical presentation and outcomes were recorded for each patient. A stroke was defined as any new focal neurological signs or symptoms with confirmatory neuroimaging revealing an infarct in a localizing territory. Early events were defined as any stroke, hemorrhage, or death that occurred within 30 days of revascularization, regardless of vascular territory, in accordance with the primary endpoint of the SAMMPRIS trial.2 Late complications (>30 days after revascularization) were considered as stroke or hemorrhage within the treated territory or any stroke, hemorrhage, or death following a subsequent treatment of the revascularized territory. Morbidity was defined as any permanent neurologic deficit following attempted BMCS placement. Mortality was defined as any death attributable to attempted BMCS placement.
Statistical analysis Data are presented as median or mean and range for continuous variables, and as frequency and per cent for categorical variables. Statistical analyses of categorical variables was carried out using χ2, Fisher’s exact test, and Wilcoxon rank sum test as appropriate. Kaplan–Meier survival analysis was calculated, and comparison was carried out using the log rank test and Cox regression analysis to determine HRs and 95% CIs. A p value of ≤0.05 was considered statistically significant. 2
Patient demographics (n=39) Age (years) (mean±SD [range]) Male sex (n (%)) Qualifying event (n=42 lesions) (n (%)) Stroke TIA Vertebrobasilar insufficiency Risk factors (n=39 patients) (n (%)) Smoking Hypertension Dyslipidemia Diabetes Lesion characteristics (n=42)* Degree of stenosis (%) (mean±SD [range]) Categorical breakdown of degree of stenosis (n (%)) 70–79% 80–89% 90–100% Location of stenosis (n (%)) Internal carotid artery Middle cerebral artery Vertebral artery Basilar artery
Value
60.3±12.1 [30–80] 24 (62) 29 (69) 8 (19) 5 (12) 17 (44) 35 (90) 34 (87) 19 (49) 80.8±10.6 [70–100] 21 (50) 6 (14) 15 (36) 7 (17) 13 (31) 14 (33) 8 (19)
Values are given as number (%) of patients within the group unless otherwise specified. TIA, transient ischemic attack.
Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Ischemic stroke Table 2 Clinical and angiographic outcomes following bare metal coronary stent placement within the intracranial circulation Characteristic
Value
Clinical outcomes (n (%)) Morbidity, cumulative 4 (9) Early infarction (within 30 days) 3 (7) Late infarction (after 30 days) 1 (2) All complications 6 (14) Early complications (within 30 days) 4 (9) Late complications (after 30 days) 2 (5) Mortality (n (%)) 0 (0) Procedural/imaging outcomes Technical success 41 (98) Immediate outcomes Residual stenosis (%) (mean±SD [range]) 11.1±15.2 [0–75] Long term outcomes (>12 months of imaging follow-up) (n (%)) No of patients 25 Stent occlusions 1 (4) Restenosis 5 (20) Retreatments 2 (8) Values are given as number (%) of patients within the group unless otherwise specified.
Periprocedural morbidity (30 days) was 2% (one patient). This occurred in a patient who underwent stenting of the left middle cerebral artery. He developed an infarction after his aspirin and clopidogrel were discontinued due to a gastrointestinal bleed.
Clinical outcomes Clinical evaluation by a neurologist 30 days postprocedure was available in 40 of 42 cases (95%), with an average of 32.1 ±24.5 months. Two patients were lost to follow-up despite multiple attempts to contact them. Overall, there was a trend toward improved outcomes following treatment of an ICS with
Figure 2 Modified Rankin Scale (mRS) score for all patients at presentation and discharge following stenting, and for those with a clinical follow-up of at least 12 months (30 patients). a BMCS (figure 2). At presentation, 55% of patients presented with a modified Rankin Scale score of ≤2. At follow-up, 74% of patients had a favorable outcome. Some of this improvement may be attributable to the natural progression of symptomatic improvement following a stroke. However, 27 of the 39 patients (69%) reported improvement in their symptoms. Over time, three of the 27 patients (11%) who initially reported symptomatic improvement subsequently developed recurrence of their initial symptoms. A univariate analysis did not identify any patient or lesion characteristics as predictive of symptom improvement or recurrence. The one death reported in figure 2 occurred as a result of complications related to the patient’s metastatic ovarian cancer.
Radiographic outcomes Imaging outcomes were available for 39 stents (93%) at 3 months, 30 stents (71%) at 6 months, and 25 stents (60%) at 12 months. Of those with at least 6 months of postprocedural imaging, the average follow-up was 35.1±22.4 months. Six patients (20%) developed moderate (>50%) in-stent stenosis at an average of 12.7±17.8 months (range 2–49 months) posttreatment. In four cases, the restenosis was measured as 50– 60%. The other two cases had 70% and 95% stenoses. Three (10%) of these in-stent stenoses required treatment, including the 70% and 95% stenoses, as well as one of the 60% stenoses that was symptomatic. All three cases were retreated with angioplasty alone. Two of the cases remained stable after treatment. However, the third required a second and third retreatment with placement of an additional stent. Since placing the second stent, this ICS has remained stable and the stent patent on subsequent follow-up evaluations.
DISCUSSION
Figure 1 Cumulative risk analysis of all complications by treated territories. Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Based on results from the SAMMPRIS trial, patients with a symptomatic ICS are more likely to receive benefit from aggressive medical therapy alone than with percutaneous transluminal angioplasty and stenting of a stenotic lesion using the Wingspan stent system.2 8 However, these patients remain at high risk for subsequent stroke, with one study estimating a 19% risk of stroke at 1 year in patients with a stenosis of >70%.1 Additionally, many patients struggle to achieve or maintain the 3
Ischemic stroke aggressive goals set forth for control of their stroke risk factors.9 These results suggest a real need for alternative effective treatment options for symptomatic intracranial stenoses. Our results suggest that BMCS are a technically viable option, with a 98% success rate, a periprocedural and overall morbidity of 7.1% and 9.5%, respectively, and a restenosis and retreatment rate of 20% and 10%, respectively. Our 30 day periprocedural morbidity was 7.1%. Other studies of BMCS deployment across intracranial stenoses have reported similar results, with an average periprocedural morbidity of 7.4% in 339 patients (range 5.6–22.7%).3 10 11 Reported periprocedural morbidity rates following Wingspan use may be higher, with an average periprocedural morbidity of 9.9% in 497 patients (range 4.4–14.7%), including a 14.7% periprocedural morbidity rate following Wingspan deployment in the SAMMPRIS trial.2 12–14 The potential for increased risk with the Wingspan stent may due to the four step deployment procedure when using a Wingspan stent. First, an angioplasty is required, then an exchange, followed by placement of the stent, and sometimes re-angioplasty. Additionally, Wingspan is not a rapid exchange system, which necessitates maintenance of the system and catheter exchanges over a 300 cm microguidewire during the procedure. Complications can occur at every step, potentially increasing the likelihood of periprocedural events, including vessel injury, thrombus formation, or distal emboli. Exchange maneuvers risk wire perforation and hemorrhage (exacerbated by dual platelet inhibition therapy), and multiple angioplasties risk vessel rupture. In contrast, BMCS requires a single step process without the need for an exchange procedure. While periprocedural morbidity rates following BMCS deployment are higher than the 5.8% 30 day morbidity within the medical arm of the SAMMPRIS trial, there may be some long term benefit to treatment.2 Our overall morbidity of 9.5% with an average clinical follow-up time of 32.1±24.5 months is similar to the average reported overall morbidity of 8.8% in 282 patients (range 7–9.8%) reported in the literature.11 15 The overall morbidity following Wingspan placement was 19.4% in 431 patients (range 7.1–23%), as reported in the literature.2 12 14 16 As a comparison, patients in the SAMMPRIS trial who were treated with aggressive medical therapy continued to have strokes well beyond the 30 day time period. The probability of a stroke at 1 year in patients treated with aggressive medical therapy alone was 12.2%,2 which is higher than the reported long term morbidity following BMCS placement.11 15 In the recently published final results of the SAMMPRIS trial, the authors cite a 15% overall morbidity in the medical treatment arm over a median follow-up of 32.4 months.8 It would be expected that patients who undergo a procedure are at greater periprocedural risk, in part due to the inherent risk involved in any procedure. However, the territory beyond a critical stenosis remains at high risk for injury, either in the setting of a drop in blood pressure or thromboembolism. In the scenario of persistent or recurrent cerebrovascular symptoms referable to the territory of an ICS despite best medical therapy, our data suggest that opening the stenosis with a stent may offer less risk to the patient than the 1 year risk reported in SAMMPRIS, and may also benefit the patient in the long term. Although a subjective and uncontrolled assessment, 27 of our 39 patients (69%) reported improvement in their symptoms following BMCS placement across their ICS. In this retrospective study, it is difficult to ascertain how much of this symptomatic improvement is related to the stent and how much is due to the natural recovery process following a stroke. However, we can isolate the patients who presented with vertebrobasilar insufficiency in our analysis to 4
find that three of the five patients (60%) had resolution of their symptoms. Similarly, five of the nine patients (55%) who presented following transient ischemic attacks reported that their recurrent symptoms had ceased following stenting. Unfortunately, three of the 27 patients who reported initial symptomatic improvement developed recurrent symptoms. In one case where the patient initially presented with transient ischemic attacks, the symptoms recurred 6 months after treatment. In the other two patients, the symptoms recurred 2 and 3 years after stenting, and both patients were found to have in-stent restenosis, requiring retreatment. Six of 30 patients (20%) with at least 6 months of radiographic follow-up developed at least a moderate (>50%) in-stent stenosis. This rate is within the range of restenosis reported in the literature following BMCS placement (12.5– 20.2%) and Wingspan placement (17.4–34.5%).3 10 13 14 16 17 In three cases, the hyperplasia stabilized and the patients remained asymptomatic. Only three (10%) of the restenoses required retreatment due to significant hyperplasia (>70%) or due to recurrent symptoms. Two of the retreatments required angioplasty alone, while one case required multiple retreatments, including placement of a second stent. However, it is our experience that eventually the neointimal hyperplasia will stabilize and no further treatments are necessary. Limitations of this study include the retrospective nature of this uncontrolled study. As this study was carried out at a tertiary referral center, selection bias is also a potential limitation. Additionally, there may be a selection bias toward lesions that were likely to be technically or anatomically feasible for stenting. While the decision to proceed with intracranial stenting stemmed from recurrent events despite aggressive medical therapy, we did not consistently implement the lifestyle modifications and additional risk factor management as regimented in the SAMMPRIS trial. However, all patients were managed by a vascular neurologist prior to their referral for stenting.
CONCLUSIONS This study suggests that BCMS used off-label for stenting of symptomatic intracranial stenosis is a technically viable alternative to the Wingspan stent system for patients who experience a stroke or transient ischemic attack in spite of best medical therapy. Additionally, morbidity following BMCS deployment seems to stabilize after the first 30 days, which may suggest that BMCS could provide a long term benefit to symptomatic patients with ICS. Prospective comparison trials of BMCS for symptomatic intracranial stenoses are warranted to determine the safest and most effective method for endovascular treatment of ICS in this high risk patient population. Contributors All authors were engaged in the conception and design of the study, manuscript review, manuscript editing, and final approval of the manuscript. CRD, SRG, KR, and SM were involved in data collection and organization. CRD and SRG drafted the article. CRD and RMS performed all of the statistical analyses. Competing interests None. Ethics approval The study was approved by the University of Virginia institutional review board. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 2 3
Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005;352:1305–16. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993–1003. Fiorella D, Chow MM, Anderson M, et al. A 7-year experience with balloon-mounted coronary stents for the treatment of symptomatic vertebrobasilar intracranial atheromatous disease. Neurosurgery 2007;61:236–42.
Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
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Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 2006;113:555–63. Zhao LB, Park S, Lee D, et al. Mechanism of procedural failure related to Wingspan. Neurointervention 2012;7:102–8. Derdeyn CP, Fiorella D, Lynn MJ, et al. Impact of operator and site experience on outcomes after angioplasty and stenting in the SAMMPRIS trial. J Neurointerv Surg 2013;5:528–33. Fox AJ. How to measure carotid stenosis. Radiology 1993;186:316–18. Derdeyn CP, Chimowitz MI, Lynn MJ, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2013;383:333–41. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123: e18–e209. Miao ZR, Feng L, Li S, et al. Treatment of symptomatic middle cerebral artery stenosis with balloon-mounted stents: long-term follow-up at a single center. Neurosurgery 2009;64:79–84. Alurkar A, Karanam LS, Oak S, et al. Role of balloon-expandable stents in intracranial atherosclerotic disease in a series of 182 patients. Stroke 2013;44:2000–3.
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17
Henkes H, Miloslavski E, Lowens S, et al. Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan). Neuroradiology 2005;47:222–8. Fiorella D, Levy EI, Turk AS, et al. US multicenter experience with the Wingspan stent system for the treatment of intracranial atheromatous disease: periprocedural results. Stroke 2007;38:881–7. Zaidat OO, Klucznik R, Alexander MJ, et al. The NIH registry on use of the Wingspan stent for symptomatic 70–99% intracranial arterial stenosis. Neurology 2008;70:1518–24. Suh DC, Kim JK, Choi JW, et al. Intracranial stenting of severe symptomatic intracranial stenosis: results of 100 consecutive patients. AJNR Am J Neuroradiol 2008;29:781–5. Costalat V, Maldonado IL, Vendrell JF, et al. Endovascular treatment of symptomatic intracranial stenosis with the Wingspan stent system and Gateway PTA balloon: a multicenter series of 60 patients with acute and midterm results. J Neurosurg 2011;115:686–93. Levy EI, Turk AS, Albuquerque FC, et al. Wingspan in-stent restenosis and thrombosis: incidence, clinical presentation, and management. Neurosurgery 2007;61:644–50.
5
ORIGINAL RESEARCH
Stenting of symptomatic intracranial stenosis using balloon mounted coronary stents: a single center experience Christopher R Durst,1 Scott R Geraghty,2 Andrew M Southerland,3 Robert M Starke,4 Karen Rembold,5 Shaneela Malik,6 Max Wintermark,1 Kenneth C Liu,4 R Webster Crowley,4 John Gaughen,1 Mary E Jensen,1 Avery J Evans1 1
Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia, USA 2 Advocate Neurovascular Center, Chicagoland, Illinois, USA 3 Department of Neurology, University of Virginia Health System, Charlottesville, Virginia, USA 4 Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia, USA 5 Department of Neurology, Tufts Medical Center, Boston, Massachusetts, USA 6 Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA Correspondence to Dr C R Durst, University of Virginia Health Systems, Department of Radiology and Medical Imaging, PO Box 800170, Charlottesville, VA 22908, USA; [email protected] CRD and SRG contributed equally. Received 21 February 2014 Accepted 3 March 2014
ABSTRACT Objective Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks. Intracranial stenting with off-label balloon mounted coronary stents (BMCS) may be a viable alternative for patients with symptomatic intracranial stenosis who fail best medical therapy. Design Between December 2005 and June 2012, 42 symptomatic intracranial stenoses were treated with a BMCS after failing medical management. Procedural records, clinical outcomes, and imaging follow-up were reviewed. Outcome measurements included technical success rate, morbidity and mortality, long term stent patency, and clinical outcomes, as measured by the modified Rankin Scale. Results The technical success rate was 98% (41 of 42 lesions). Morbidity within the first 30 days was 7.1% (three of 42 lesions). Overall morbidity, including both periprocedural and long term evaluation, was 9.5% (four of 42 lesions). There were no deaths. Follow-up imaging was available for 30 stents (71%) with an average follow-up time of 35.1 months. Restenosis (>50%) and retreatment were observed in 20% and 10% of cases, respectively. Clinical evaluation by a neurologist ≥30 days postprocedure was available in 40 of 42 cases (95%) with an average of 32.1 months. At presentation, 55% of patients had a modified Rankin Scale (mRS) score of ≤2. At follow-up, 74% of patients were found to have an mRS score of ≤2. Conclusions This study suggests that BMCS may benefit patients with symptomatic intracranial stenosis who experience stroke or transient ischemic attack in spite of best medical therapy.
risk.2 The Wingspan system is criticized for being bulky and requiring a multi-step deployment.5 6 In contrast, balloon mounted coronary stents (BMCS) can be deployed in a single step, eliminating the number of exchanges required for deployment of a Wingspan stent. We hypothesize that intracranial stenting with off-label BMCS would be an uncomplicated, clinically viable alternative for patients with symptomatic ICS who fail best medical therapy.
PATIENTS AND METHODS Study design This study was performed under the auspices of our institutional review board. At our institution, all patients who present with an ICS (defined as >70% stenosis) are treated with aggressive medical management, based on the results of the WASID (Warfarin–Aspirin Symptomatic Intracranial Disease) and SAMMPRIS trials as a guideline.1 2 Patients are only considered for intracranial stenting after they have failed best medical management, defined as recurrent ischemic symptoms localizing to the stenotic arterial territory. A retrospective chart review identified 39 patients with 42 symptomatic lesions, despite best medical management, who subsequently underwent attempted BMCS placement between December 2005 and June 2012. All clinical and imaging outcomes were independently adjudicated by vascular neurologists and diagnostic neuroradiologists, respectively, unaffiliated with the procedure.
Procedural technique OBJECTIVE
To cite: Durst CR, Geraghty SR, Southerland AM, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011185
Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks, resulting in significant morbidity and mortality.1 Even with best medical therapy, the risk of recurrent stroke remains high.2–4 The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial demonstrated that intracranial stenting for symptomatic intracranial stenosis (ICS) (70–99%) with the Wingspan stent system (Stryker Neurovascular, Fremont, California, USA) is significantly more dangerous than best medical management, primarily driven by periprocedural stroke
Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Written informed consent was obtained for all procedures. All patients were placed on dual antiplatelet therapy (aspirin 325 mg and clopidogrel 75 mg) prior to stenting. For patients on clopidogrel, preprocedure platelet reactivity assay was checked using the VerifyNow P2Y12 test (Accumetrics, San Diego, California, USA). If subtherapeutic, patients were given a clopidogrel ‘load’ (300 or 600 mg) and rechecked. If they remained subtherapeutic, patients were prescribed thienopyridine and rescheduled for a later procedure. Patients were to continue taking aspirin for life and clopidogrel (or, alternatively, thienopyridine in clopidogrel nonresponders) for 90 days following stent placement. 1
Ischemic stroke All procedures were performed under general anesthesia. Access was obtained in a standard fashion. Intravenous heparin was administered during the procedure to achieve an activated coagulation time of between 250 and 300 s. A BMCS (Multi-Link Vision cobalt–chromium coronary stent; Abbott Vascular, Abbott Laboratories, Abbott Park, Illinois, USA) was advanced over a microguidewire across the intracranial stenosis using roadmap guidance. Digital subtraction angiography (DSA) was performed through the guide catheter prior to stent deployment to confirm appropriate stent positioning. The stent was then slowly deployed over several minutes using intermittent fluoroscopy, inflating approximately 1 atm every 30–60 s initially. After reaching the desired inflation, the balloon was deflated and removed, leaving the stent in place. Immediate post-stenting DSA was performed, as well as post 10 and 20 min DSA to ensure there was no thrombus formation in the stent or distal thromboembolism. Heparin anticoagulation was not reversed following the procedure. Patients were observed in a neurocritical care unit for 24 h postprocedure to monitor neurological examination and new events, and ensure hemostasis at the femoral site.
RESULTS Patient demographics and lesion characteristics
Procedural outcomes
Endovascular related complications
In all cases, pretreatment and immediate post-treatment ICS was measured by DSA using standard measurement methods.7 Treatment studies were evaluated for complications related to stent deployment, including failed deployment, inappropriate positioning of the stent, vessel injury, or thromboembolic events. At discharge, patients were scheduled for a 3–6 month angiographic follow-up with intent to image via CT angiography, MR angiography, or additional angiographic studies at 12 and 24 months. Follow-up imaging was evaluated for stent patency, recurrent stenosis, and stent related vascular complications. A recurrent stenosis was defined as stenosis greater than 50% compared with the angiography images acquired at the end of the procedural study.
Overall treatment related morbidity, including periprocedural and late events, was 9.5% (four patients). Mortality was 0%. Each of the morbid events involved a clinical stroke with diffusion weighted imaging correlate involving the treated vascular territory. A univariate analysis did not identify any of the patient demographics or lesion characteristics as predictors of outcome. A risk analysis (figure 1) identified the posterior circulation as experiencing more complications at an earlier time point, although this did not reach statistical significance ( p=0.124).
Between December 2005 and June 2012, BMCS was attempted in 39 patients with 42 symptomatic intracranial stenoses. Three patients had more than one stenosis that required treatment. In one patient, the lesions were in tandem within one vascular territory. In the other two patients, the lesions were in opposite hemispheres. Twenty-two lesions were in the posterior circulation and 20 in the anterior circulation. Mean age was 60 years, with 38% women (table 1).
Technical success A total of 41 stents were successfully placed across 42 lesions for a technical success rate of 98% (table 2). In one case the BMCS could not be advanced beyond a tortuous siphon to stent a distal right internal carotid artery stenosis. This lesion was instead treated with balloon angioplasty only. One stenosis required pre-dilation with balloon angioplasty. The remainder of the cases were performed without pre-dilation. Post-dilation was not required in any case. In one case of basilar artery stenosis, the BMCS was deployed inside a stenotic Wingspan stent.
Table 1
Patient demographics and lesion characteristics
Characteristic
Clinical assessment Through a thorough review of the medical records, the clinical presentation and outcomes were recorded for each patient. A stroke was defined as any new focal neurological signs or symptoms with confirmatory neuroimaging revealing an infarct in a localizing territory. Early events were defined as any stroke, hemorrhage, or death that occurred within 30 days of revascularization, regardless of vascular territory, in accordance with the primary endpoint of the SAMMPRIS trial.2 Late complications (>30 days after revascularization) were considered as stroke or hemorrhage within the treated territory or any stroke, hemorrhage, or death following a subsequent treatment of the revascularized territory. Morbidity was defined as any permanent neurologic deficit following attempted BMCS placement. Mortality was defined as any death attributable to attempted BMCS placement.
Statistical analysis Data are presented as median or mean and range for continuous variables, and as frequency and per cent for categorical variables. Statistical analyses of categorical variables was carried out using χ2, Fisher’s exact test, and Wilcoxon rank sum test as appropriate. Kaplan–Meier survival analysis was calculated, and comparison was carried out using the log rank test and Cox regression analysis to determine HRs and 95% CIs. A p value of ≤0.05 was considered statistically significant. 2
Patient demographics (n=39) Age (years) (mean±SD [range]) Male sex (n (%)) Qualifying event (n=42 lesions) (n (%)) Stroke TIA Vertebrobasilar insufficiency Risk factors (n=39 patients) (n (%)) Smoking Hypertension Dyslipidemia Diabetes Lesion characteristics (n=42)* Degree of stenosis (%) (mean±SD [range]) Categorical breakdown of degree of stenosis (n (%)) 70–79% 80–89% 90–100% Location of stenosis (n (%)) Internal carotid artery Middle cerebral artery Vertebral artery Basilar artery
Value
60.3±12.1 [30–80] 24 (62) 29 (69) 8 (19) 5 (12) 17 (44) 35 (90) 34 (87) 19 (49) 80.8±10.6 [70–100] 21 (50) 6 (14) 15 (36) 7 (17) 13 (31) 14 (33) 8 (19)
Values are given as number (%) of patients within the group unless otherwise specified. TIA, transient ischemic attack.
Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Ischemic stroke Table 2 Clinical and angiographic outcomes following bare metal coronary stent placement within the intracranial circulation Characteristic
Value
Clinical outcomes (n (%)) Morbidity, cumulative 4 (9) Early infarction (within 30 days) 3 (7) Late infarction (after 30 days) 1 (2) All complications 6 (14) Early complications (within 30 days) 4 (9) Late complications (after 30 days) 2 (5) Mortality (n (%)) 0 (0) Procedural/imaging outcomes Technical success 41 (98) Immediate outcomes Residual stenosis (%) (mean±SD [range]) 11.1±15.2 [0–75] Long term outcomes (>12 months of imaging follow-up) (n (%)) No of patients 25 Stent occlusions 1 (4) Restenosis 5 (20) Retreatments 2 (8) Values are given as number (%) of patients within the group unless otherwise specified.
Periprocedural morbidity (30 days) was 2% (one patient). This occurred in a patient who underwent stenting of the left middle cerebral artery. He developed an infarction after his aspirin and clopidogrel were discontinued due to a gastrointestinal bleed.
Clinical outcomes Clinical evaluation by a neurologist 30 days postprocedure was available in 40 of 42 cases (95%), with an average of 32.1 ±24.5 months. Two patients were lost to follow-up despite multiple attempts to contact them. Overall, there was a trend toward improved outcomes following treatment of an ICS with
Figure 2 Modified Rankin Scale (mRS) score for all patients at presentation and discharge following stenting, and for those with a clinical follow-up of at least 12 months (30 patients). a BMCS (figure 2). At presentation, 55% of patients presented with a modified Rankin Scale score of ≤2. At follow-up, 74% of patients had a favorable outcome. Some of this improvement may be attributable to the natural progression of symptomatic improvement following a stroke. However, 27 of the 39 patients (69%) reported improvement in their symptoms. Over time, three of the 27 patients (11%) who initially reported symptomatic improvement subsequently developed recurrence of their initial symptoms. A univariate analysis did not identify any patient or lesion characteristics as predictive of symptom improvement or recurrence. The one death reported in figure 2 occurred as a result of complications related to the patient’s metastatic ovarian cancer.
Radiographic outcomes Imaging outcomes were available for 39 stents (93%) at 3 months, 30 stents (71%) at 6 months, and 25 stents (60%) at 12 months. Of those with at least 6 months of postprocedural imaging, the average follow-up was 35.1±22.4 months. Six patients (20%) developed moderate (>50%) in-stent stenosis at an average of 12.7±17.8 months (range 2–49 months) posttreatment. In four cases, the restenosis was measured as 50– 60%. The other two cases had 70% and 95% stenoses. Three (10%) of these in-stent stenoses required treatment, including the 70% and 95% stenoses, as well as one of the 60% stenoses that was symptomatic. All three cases were retreated with angioplasty alone. Two of the cases remained stable after treatment. However, the third required a second and third retreatment with placement of an additional stent. Since placing the second stent, this ICS has remained stable and the stent patent on subsequent follow-up evaluations.
DISCUSSION
Figure 1 Cumulative risk analysis of all complications by treated territories. Durst CR, et al. J NeuroIntervent Surg 2014;0:1–5. doi:10.1136/neurintsurg-2014-011185
Based on results from the SAMMPRIS trial, patients with a symptomatic ICS are more likely to receive benefit from aggressive medical therapy alone than with percutaneous transluminal angioplasty and stenting of a stenotic lesion using the Wingspan stent system.2 8 However, these patients remain at high risk for subsequent stroke, with one study estimating a 19% risk of stroke at 1 year in patients with a stenosis of >70%.1 Additionally, many patients struggle to achieve or maintain the 3
Ischemic stroke aggressive goals set forth for control of their stroke risk factors.9 These results suggest a real need for alternative effective treatment options for symptomatic intracranial stenoses. Our results suggest that BMCS are a technically viable option, with a 98% success rate, a periprocedural and overall morbidity of 7.1% and 9.5%, respectively, and a restenosis and retreatment rate of 20% and 10%, respectively. Our 30 day periprocedural morbidity was 7.1%. Other studies of BMCS deployment across intracranial stenoses have reported similar results, with an average periprocedural morbidity of 7.4% in 339 patients (range 5.6–22.7%).3 10 11 Reported periprocedural morbidity rates following Wingspan use may be higher, with an average periprocedural morbidity of 9.9% in 497 patients (range 4.4–14.7%), including a 14.7% periprocedural morbidity rate following Wingspan deployment in the SAMMPRIS trial.2 12–14 The potential for increased risk with the Wingspan stent may due to the four step deployment procedure when using a Wingspan stent. First, an angioplasty is required, then an exchange, followed by placement of the stent, and sometimes re-angioplasty. Additionally, Wingspan is not a rapid exchange system, which necessitates maintenance of the system and catheter exchanges over a 300 cm microguidewire during the procedure. Complications can occur at every step, potentially increasing the likelihood of periprocedural events, including vessel injury, thrombus formation, or distal emboli. Exchange maneuvers risk wire perforation and hemorrhage (exacerbated by dual platelet inhibition therapy), and multiple angioplasties risk vessel rupture. In contrast, BMCS requires a single step process without the need for an exchange procedure. While periprocedural morbidity rates following BMCS deployment are higher than the 5.8% 30 day morbidity within the medical arm of the SAMMPRIS trial, there may be some long term benefit to treatment.2 Our overall morbidity of 9.5% with an average clinical follow-up time of 32.1±24.5 months is similar to the average reported overall morbidity of 8.8% in 282 patients (range 7–9.8%) reported in the literature.11 15 The overall morbidity following Wingspan placement was 19.4% in 431 patients (range 7.1–23%), as reported in the literature.2 12 14 16 As a comparison, patients in the SAMMPRIS trial who were treated with aggressive medical therapy continued to have strokes well beyond the 30 day time period. The probability of a stroke at 1 year in patients treated with aggressive medical therapy alone was 12.2%,2 which is higher than the reported long term morbidity following BMCS placement.11 15 In the recently published final results of the SAMMPRIS trial, the authors cite a 15% overall morbidity in the medical treatment arm over a median follow-up of 32.4 months.8 It would be expected that patients who undergo a procedure are at greater periprocedural risk, in part due to the inherent risk involved in any procedure. However, the territory beyond a critical stenosis remains at high risk for injury, either in the setting of a drop in blood pressure or thromboembolism. In the scenario of persistent or recurrent cerebrovascular symptoms referable to the territory of an ICS despite best medical therapy, our data suggest that opening the stenosis with a stent may offer less risk to the patient than the 1 year risk reported in SAMMPRIS, and may also benefit the patient in the long term. Although a subjective and uncontrolled assessment, 27 of our 39 patients (69%) reported improvement in their symptoms following BMCS placement across their ICS. In this retrospective study, it is difficult to ascertain how much of this symptomatic improvement is related to the stent and how much is due to the natural recovery process following a stroke. However, we can isolate the patients who presented with vertebrobasilar insufficiency in our analysis to 4
find that three of the five patients (60%) had resolution of their symptoms. Similarly, five of the nine patients (55%) who presented following transient ischemic attacks reported that their recurrent symptoms had ceased following stenting. Unfortunately, three of the 27 patients who reported initial symptomatic improvement developed recurrent symptoms. In one case where the patient initially presented with transient ischemic attacks, the symptoms recurred 6 months after treatment. In the other two patients, the symptoms recurred 2 and 3 years after stenting, and both patients were found to have in-stent restenosis, requiring retreatment. Six of 30 patients (20%) with at least 6 months of radiographic follow-up developed at least a moderate (>50%) in-stent stenosis. This rate is within the range of restenosis reported in the literature following BMCS placement (12.5– 20.2%) and Wingspan placement (17.4–34.5%).3 10 13 14 16 17 In three cases, the hyperplasia stabilized and the patients remained asymptomatic. Only three (10%) of the restenoses required retreatment due to significant hyperplasia (>70%) or due to recurrent symptoms. Two of the retreatments required angioplasty alone, while one case required multiple retreatments, including placement of a second stent. However, it is our experience that eventually the neointimal hyperplasia will stabilize and no further treatments are necessary. Limitations of this study include the retrospective nature of this uncontrolled study. As this study was carried out at a tertiary referral center, selection bias is also a potential limitation. Additionally, there may be a selection bias toward lesions that were likely to be technically or anatomically feasible for stenting. While the decision to proceed with intracranial stenting stemmed from recurrent events despite aggressive medical therapy, we did not consistently implement the lifestyle modifications and additional risk factor management as regimented in the SAMMPRIS trial. However, all patients were managed by a vascular neurologist prior to their referral for stenting.
CONCLUSIONS This study suggests that BCMS used off-label for stenting of symptomatic intracranial stenosis is a technically viable alternative to the Wingspan stent system for patients who experience a stroke or transient ischemic attack in spite of best medical therapy. Additionally, morbidity following BMCS deployment seems to stabilize after the first 30 days, which may suggest that BMCS could provide a long term benefit to symptomatic patients with ICS. Prospective comparison trials of BMCS for symptomatic intracranial stenoses are warranted to determine the safest and most effective method for endovascular treatment of ICS in this high risk patient population. Contributors All authors were engaged in the conception and design of the study, manuscript review, manuscript editing, and final approval of the manuscript. CRD, SRG, KR, and SM were involved in data collection and organization. CRD and SRG drafted the article. CRD and RMS performed all of the statistical analyses. Competing interests None. Ethics approval The study was approved by the University of Virginia institutional review board. Provenance and peer review Not commissioned; externally peer reviewed.
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