Journal of Clinical Neuroscience 21 (2014) 274–277
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Stenting of symptomatic vertebral artery ostium stenosis with self-expanding stents Zifu Li a, , Yongwei Zhang b, , Bo Hong a, Benqiang Deng b, Yi Xu a, Wenyuan Zhao a, Jianmin Liu a,⇑, Qinghai Huang a a b
Department of Neurosurgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China Department of Neurology, Changhai Hospital, Second Military Medical University, Department of Neurosurgery, Shanghai, China
a r t i c l e
i n f o
Article history: Received 21 February 2013 Accepted 6 April 2013
Keywords: Self-expanding stent Stenosis Stenting Vertebral artery ostium
a b s t r a c t Symptomatic vertebral arterial stenosis carries a stroke risk of 30% at 5 years. The efficacy of stenting with balloon-expandable stents remains questionable due to a high long-term restenosis rate. This study aimed to investigate the feasibility and efficacy of using self-expanding stents to treat symptomatic vertebral artery ostium (VAO) stenosis in selected patients. Clinical and angiographic results were retrospectively reviewed in patients with symptomatic VAO stenosis who underwent stenting with self-expanding stents between June 2008 and December 2011. In total, 32 patients were included. Self-expanding stents (25 tapered and seven non-tapered) were deployed with a modified technique of deploying the stents from the V1 segment to the proximal subclavian artery. The mean degree of stenosis before and after stenting declined from 76.4% to 11.4%. No peri-procedural complications occurred. During the mean clinical follow-up of 18.3 months, no vertebrobasilar stroke, transient ischemic attack or death occurred. During the mean angiographic follow-up of 12.5 months, asymptomatic restenosis occurred in one (3.1%) patient 6 months after the procedure. No stent fracture occurred. The involved subclavian artery was patent and no clinically apparent events occurred in the dependent upper extremity. Stenting with self-expanding stents for symptomatic VAO stenosis is technically feasible and safe, with reduced restenosis and stent fracture rates in selected patients. Long-term investigations are warranted to validate its performance. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Posterior circulation stroke accounts for about 20% of all ischemic stroke, usually carrying high rates of morbidity and mortality. Approximately one third of posterior circulation strokes are attributed to severe occlusive lesions (P50%) in the extracranial vertebral artery (VA), especially the ostium.1,2 Although the absolute risk of posterior circulation ischemic stroke for asymptomatic stenosis remains low,3 the stroke risk increases significantly for symptomatic VA stenosis and reaches 30% at 5 years.4,5 Compelling evidence to determine the optimal therapy for symptomatic VA stenosis is still lacking. Surgical procedures are useful to reconstruct the stenotic lumen but are rarely performed due to perioperative complications.6 The randomized Vertebral Artery Stenting Trial to compare stenting with medical therapy is ongoing.7 So far, medical therapy plus risk factor control remains the mainstay of therapy. For medically refractory stenosis, stenting
⇑ Corresponding author. Tel./fax: +86 21 31161784.
E-mail address: [email protected] (J. Liu). These authors have contributed equally to the work.
0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.04.022
with balloon-expandable stents (BES) enjoys wide popularity due to its high technical success and low complication rate,8,9 but its long-term efficacy remains questionable due to high rates of instent restenosis and stent fracture.10 Self-expanding stents (SES) are designed with high flexibility and enhanced radial expansion force. Thus stenting with SES has the potential of reducing rates of in-stent restenosis and stent fracture. However, available information concerning stenting with SES for vertebral artery ostium (VAO) stenosis is limited. In this study, we present our experiences of stenting with SES to treat symptomatic VAO stenosis in selected patients.
2. Materials and methods 2.1. Study design and patient selection A retrospective study was conducted with patients treated with SES between June 2008 and December 2011 selected from the Interventional Database. Medical records were reviewed to collect data on baseline characteristics including clinical symptoms, risk factors, procedural results, and in-hospital and follow-up out-
Z. Li et al. / Journal of Clinical Neuroscience 21 (2014) 274–277
comes. Angiographic results were reviewed from the picture archiving and communication system (PACS) and Angiography Databank to investigate immediate and follow-up results. This study was approved by the Institutional Review Board at our hospital. The diagnosis of symptomatic VAO stenosis was based on clinical and angiographic evaluation, and was confirmed by two independent neurologists (YWZ and BQD). Clinical symptoms included stroke, transient ischemic attack (TIA), vertigo, ataxia and visual disturbance. Patients were considered suitable to undergo stenting when they met the following inclusion criteria: (1) medically refractory symptoms related to VAO stenosis; and (2) ostial stenosis P70% with at least two risk factors for atherosclerosis. Exclusion criteria were the following: (1) vertebrobasilar infarction associated with diseases of small vessels or perforators or with cardiac embolism; (2) non-atherosclerotic VAO stenosis including dissection, radiation vasculopathy, vasculitis or fibromuscular dysplasia; and (3) allergies to the contrast medium or antiplatelet medication. Informed consent was obtained from each patient before the intervention.
2.2. Stenting procedure All patients received 300 mg aspirin and 75 mg clopidogrel per day for at least 5 days prior to the procedure. All patients received systemic heparin after placement of the sheath. The activated clotting time was maintained at two to three times the baseline throughout the procedure. Routine four-vessel angiography was performed via the femoral route under local anesthesia. Reference VA and subclavian artery (SA) diameters were measured on quantitative angiography. If the reference VA diameter was P4.5 mm and the diameter of reference SA was 610 mm, a SES was considered. An 8 French guiding catheter was positioned into the proximal SA, and a 0.014 inch micro-guidewire was advanced to cross the stenosis under road-mapping. After balloon pre-dilatation, the SES was carefully deployed from the V1 segment to the proximal SA (Fig. 1). Post-dilatation was performed if residual stenosis was >30%. Post-procedural anticoagulant therapy (low molecular heparin, 4000 U, every 12 hours) was administered subcutaneously for 3 days. All patients were maintained on aspirin (300 mg daily) and clopidogrel (75 mg daily) for 6 weeks, followed by aspirin alone (300 mg per day) for 6 months, which was then reduced to 100 mg daily and continued indefinitely.
275
2.3. Follow-up All follow-up observations were performed by two neurologists from our clinical center as a part of usual clinical care (YWZ and BQD). Outpatient clinic follow-up was routinely performed 30 days after the procedure and thereafter at 3 month intervals. New events of vertebrobasilar stroke, TIA, and vascular death were investigated during the follow-up period. Non-invasive imaging (CT angiography, MR angiography, duplex ultrasonography) was coupled with outpatient visits and was scheduled for 30 days and 3, 6 and 12 months after the procedure, and then annually. Digital subtraction angiography was scheduled when restenosis was suspected on non-invasive imaging, or when angiographic evaluation or intervention was performed in other vascular territories. Restenosis was defined as P50% lumen loss observed on follow-up angiography. 2.4. Data analysis All continuous data are expressed as mean ± standard deviation. The range, median, mean, and standard deviation were determined for each measurement. The technical success, restenosis and stent fracture rates of SES placement were compared with our previous results with drug-eluting stents (DES) placement. 3. Results 3.1. Baseline characteristics In total, 32 patients (28 men, four women; mean age 65.6 ± 8.6 years; range, 53–84 years) were included in the investigation. Their clinical characteristics are presented in Table 1. About one third of patients had experienced a previous stroke in the posterior circulation territory, and one third of patients had vertigo. 3.2. Stenotic characteristics The stenosis was located in the right VAO in seven patients and in the left in 25 patients. The degree of stenosis ranged from 70% to 90% (mean, 76.4 ± 6.7). The reference VA diameter ranged from 4.5 mm to 6.4 mm (mean, 5.13 ± 0.79), and the reference SA diameter ranged from 7.5 mm to 10.0 mm (mean, 8.73 ± 0.96). Of the 32 patients, 10 had concomitant stenosis (>50%) or occlusion of the contralateral VA, eight had a hypoplastic contralateral VA, seven had stenosis (>50%) of the ipsilateral SA, and six had occlusion of the unilateral internal carotid artery.
Table 1 Baseline characteristics of patients with symptomatic vertebral artery ostium stenosis
Fig. 1. Schematic drawings of the modified technique of deploying a self-expanding stent in patients with vertebral artery stenosis. The left panel shows the ostial stenosis, and the right panel shows the self-expanding stent being deployed from the V1 segment to the proximal subclavian artery.
Baseline (n = 32) Male:female Mean age (±standard deviation), years
28:4 65.6 ± 8.6
Risk factors Hypertension Diabetes Heavy smoking Alcohol addiction Hyperlipidemia Coronary heart disease
23 (71.9) 9 (28.1) 12 (37.5) 8 (25.0) 10 (31.3) 8 (25.0)
Clinical symptoms Stroke Transient ischemic attack Vertigo Ataxia Visual disturbance
11 (34.4) 3 (9.4) 10 (31.2) 6 (18.8) 2 (6.2)
Data are presented as n (%) unless otherwise stated.
276
Z. Li et al. / Journal of Clinical Neuroscience 21 (2014) 274–277
3.3. Procedural results A modified deployment technique was performed in all patients, which involved deploying the stents from the V1 segment to the proximal portion of the SA (Fig. 2). Technical success was achieved in 32 (100%) patients. In total, 25 (78%) tapered and seven (22%) non-tapered stents were deployed. The tapered stents included Protégé (ev3 Endovascular, Plymouth, MN, USA) and Acculink (Abbott Laboratories, Abbott Park, IL, USA) stents, and the non-tapered stents included Precise (Cordis Endovascular, Bridgewater, NJ, USA), Protégé (ev3 Endovascular) and Acculink (Abbott Laboratories) stents. The specifications of stents used is summarized in Table 2. Post-dilatation was performed in nine (28%) patients. The mean residual stenosis was 11.4% (range, 0–20%). 3.4. Follow-up outcomes The mean duration of clinical follow-up was 18.3 months (range, 3–34 months). No vertebrobasilar stroke, TIA or death occurred during the 30 days after stenting or during the follow-up. One patient developed a TIA related to concomitant internal carotid artery stenosis 11 months after the procedure. We performed carotid angioplasty and stenting for this patient and thereafter TIA did not occur. No ischemic events were observed in the ipsilateral upper extremity. The mean duration of angiographic follow-up was 12.5 months (range, 3–24 months). Digital subtraction angiography was performed in 12 patients, and non-invasive imaging performed in the remaining patients, with CT scans in 20 patients, MR angiography in 10 patients, and duplex ultrasonography in four patients. Restenosis (60%) was observed in one (3.1%) patient 6 months after stenting. In-stent angioplasty or stenting was not performed for this patient because the patient was asymptomatic, and medication and follow-up were continued. No stent fracture was observed. The involved SA lumen covered by the stent mesh remained patent in all patients. 4. Discussion The current study supports the feasibility and efficacy of stenting with SES in selected patients with symptomatic atherosclerotic VAO stenosis. Compared with previous results using DES,11 our
Table 2 Deployed self-expanding stent profiles used for treatment of symptomatic vertebral artery ostium stenosis (n = 32)
Diameter (mm) Length (mm) n à §
Tapered stents
Non-tapered stents
Acculink
Protégéà
Acculink
Precise§
6–8 40 5
7–10 40 10
10 30 1
8 30 1
7–10 40 10
8 40 2
Protégéà 9 30 1
8 30 2
Abbott Laboratories, Abbott Park, IL, USA. ev3 Endovascular, Plymouth, MN, USA. Cordis Endovascular, Bridgewater, NJ, USA.
data suggests that stenting with SES has the same technical success (100%), lower restenosis rate (3.1% versus 5.3%) and fracture rate (0% versus 10.5%). The mid-term follow-up also indicates that it is relatively safe to use our modified deployment technique. For symptomatic VAO stenosis, stenting with BES can be accomplished with complications being rare and the success rate high.5 However, the high long-term restenosis rate, reported to reach 20–48%, remains discouraging.12–15 Many explanations have been proposed for restenosis. VA are arteries with considerable elastic forces and pulsations which have to be counterbalanced by the radial force of a stent. The radial force of BES may be too weak for the mechanical forces of the VA. Different flexibility and contractibility between the stents and vessel wall possibly stimulate chronic inflammation. Lesion length and anatomical characteristics of the artery also influence restenosis.10,16 Compared with BES, DES can reduce restenosis rates by inhibiting neointimal hyperplasia. In our previous cohort of stenting with DES, the restenosis rate decreased to 5.3% after a mean follow-up of 28.3 months, but the stent fracture rate increased significantly.11 Furthermore, the diameter in the majority of DES is less than 5.0 mm, thus ruling out treatment of stenosis if the reference VA diameter >5.0 mm. SES have some advantages for VAO stenosis. SES are designed with more resistance to external forces than BES. The shape memory and chronic radial expansion also enable SES to better comply with pulsations, elastic forces and recoil of rigid plaques. Moreover, there is frequently a fusiform widening of the artery with changing diameters after the ostium stenosis. BES may have a limited apposition in this region. Instead, a SES placed across the VA may appose better to changing vessel diameters. In our series with the
Fig. 2. Self-expanding stent placement in a 60-year-old man with severe stenosis in the left vertebral artery ostium. (A) Digital subtraction angiography showing ostial 90% stenosis of the left vertebral artery, and (B) unsubtracted angiogram showing the morphology of the tapered stent (7–10 mm diameter, 40 mm long) deployed within the vertebral artery and subclavian artery. (C) Subtracted angiogram showing the immediate result without residual stenosis. (D) Subtracted angiogram showing the lumen is well preserved at the 2 year follow-up.
Z. Li et al. / Journal of Clinical Neuroscience 21 (2014) 274–277
modified deployment technique, the tapered SES was preferred because it can meet the requirements for the diameter difference between the reference SA and VA. Chung et al.17 reported 20 patients with VAO stenosis treated with SES. None of their patients had recurrent stroke after clinical follow-up of 14.8 months. Five patients had mild intima hyperplasia and no stenosis had a lumen loss >50% after angiographic follow-up of 13.7 months with Doppler ultrasound. Our results are consistent with those of Chung et al., showing the high technical success rate and low restenosis rate of stenting with SES. The restenosis rate (3.1%) in our data is slightly higher than in Chung et al. This may be attributed to the different benchmark for atherosclerosis severity. Most of our patients had concomitant occlusive internal carotid artery diseases or other vascular diseases, indicating that the study population represents more severe atherosclerotic conditions. Different follow-up protocols will also influence the results, caused by the sensitivity and specificity of the follow-up tools. In addition, our study and the one conducted by Chung et al. have a small sample size. Therefore, trials with a large population are warranted to further investigate efficacy. Differing from the traditional deployment technique, we placed the SES from the V1 segment to the proximal SA (Fig. 1). A small protrusion of the deployed stent was usually left in the SA. However, deploying the SES in a short segment of ostial stenosis is challenging. The angulation and tortuosity of the vertebral origin easily prompts the deployed stent to angulate the vessel, and rigid plaque in the ostium can also make the stent leap easily. Stent misplacement and difficulty in retrieving filter protection can be encountered.17 In our series, there was no stent misplacement. We believe that the modified deployment method is more favorable for stent positioning and release than the traditional method. Stents extending from the V1 segment to the SA bridge the two arteries with meshes, acting like a filter. These meshes produce concern regarding possible thromboembolism. In fact, the outward shape of these meshes toward the distal subclavian lumen makes them larger than usual. The mid-term follow-up in our cohort shows that no clinically apparent complication in the dependent upper extremity occurred. This implies that the influence on blood flow by these meshes is possibly minimal. There are some limitations of this study. The study is retrospective in nature, has a small size sample and a limited follow-up period. More data from a large population with long-term follow-up are required to further validate performance. Moreover, patients with reference VA diameter or =50% symptomatic vertebral or basilar artery stenosis: prospective populationbased study. Brain 2009;132:982–8. 5. Jenkins JS, Patel SN, White CJ, et al. Endovascular stenting for vertebral artery stenosis. J Am Coll Cardiol 2010;55:538–42. 6. Kakino S, Ogasawara K, Kubo Y, et al. Clinical and angiographic long-term outcomes of vertebral artery-subclavian artery transposition to treat symptomatic stenosis of vertebral artery origin. J Neurosurg 2009;110:943–7. 7. Compter A, van der Worp HB, Schonewille WJ, et al. VAST: Vertebral Artery Stenting Trial. Protocol for a randomised safety and feasibility trial. Trials 2008;9:65. 8. Hatano T, Tsukahara T, Miyakoshi A, et al. Stent placement for atherosclerotic stenosis of the vertebral artery ostium: angiographic and clinical outcomes in 117 consecutive patients. Neurosurgery 2011;68:108–16. 9. Taylor RA, Siddiq F, Memon MZ, et al. Vertebral artery ostial stent placement for atherosclerotic stenosis in 72 consecutive patients: clinical outcomes and follow-up results. Neuroradiology 2009;51:531–9. 10. Stayman AN, Nogueira RG, Gupta R. A systematic review of stenting and angioplasty of symptomatic extracranial vertebral artery stenosis. Stroke 2011;42:2212–6. 11. Chen X, Huang Q, Hong B, et al. Drug-eluting stent for the treatment of symptomatic vertebral origin stenosis: long-term results. J Clin Neurosci 2011;18:47–51. 12. Ogilvy CS, Yang X, Natarajan SK, et al. Restenosis rates following vertebral artery origin stenting: does stent type make a difference? J Invasive Cardiol 2010;22:119–24. 13. Albuquerque FC, Fiorella D, Han P, et al. A reappraisal of angioplasty and stenting for the treatment of vertebral origin stenosis. Neurosurgery 2003;53:607–14. 14. SSYLVIA Study Investigators. Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA): study results. Stroke 2004;35:1388–92. 15. Lin YH, Juang JM, Jeng JS, et al. Symptomatic ostial vertebral artery stenosis treated with tubular coronary stents: clinical results and restenosis analysis. J Endovasc Ther 2004;11:719–26. 16. Lin YH, Liu YC, Tseng WY, et al. The impact of lesion length on angiographic restenosis after vertebral artery origin stenting. Eur J Vasc Endovasc Surg 2006;32:379–85. 17. Chung SY, Lee DH, Choi JW, et al. Use of self-expanding stents for the treatment of vertebral artery ostial stenosis: a single center experience. Korean J Radiol 2010;11:156–63.
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Stenting of symptomatic vertebral artery ostium stenosis with self-expanding stents Zifu Li a, , Yongwei Zhang b, , Bo Hong a, Benqiang Deng b, Yi Xu a, Wenyuan Zhao a, Jianmin Liu a,⇑, Qinghai Huang a a b
Department of Neurosurgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China Department of Neurology, Changhai Hospital, Second Military Medical University, Department of Neurosurgery, Shanghai, China
a r t i c l e
i n f o
Article history: Received 21 February 2013 Accepted 6 April 2013
Keywords: Self-expanding stent Stenosis Stenting Vertebral artery ostium
a b s t r a c t Symptomatic vertebral arterial stenosis carries a stroke risk of 30% at 5 years. The efficacy of stenting with balloon-expandable stents remains questionable due to a high long-term restenosis rate. This study aimed to investigate the feasibility and efficacy of using self-expanding stents to treat symptomatic vertebral artery ostium (VAO) stenosis in selected patients. Clinical and angiographic results were retrospectively reviewed in patients with symptomatic VAO stenosis who underwent stenting with self-expanding stents between June 2008 and December 2011. In total, 32 patients were included. Self-expanding stents (25 tapered and seven non-tapered) were deployed with a modified technique of deploying the stents from the V1 segment to the proximal subclavian artery. The mean degree of stenosis before and after stenting declined from 76.4% to 11.4%. No peri-procedural complications occurred. During the mean clinical follow-up of 18.3 months, no vertebrobasilar stroke, transient ischemic attack or death occurred. During the mean angiographic follow-up of 12.5 months, asymptomatic restenosis occurred in one (3.1%) patient 6 months after the procedure. No stent fracture occurred. The involved subclavian artery was patent and no clinically apparent events occurred in the dependent upper extremity. Stenting with self-expanding stents for symptomatic VAO stenosis is technically feasible and safe, with reduced restenosis and stent fracture rates in selected patients. Long-term investigations are warranted to validate its performance. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Posterior circulation stroke accounts for about 20% of all ischemic stroke, usually carrying high rates of morbidity and mortality. Approximately one third of posterior circulation strokes are attributed to severe occlusive lesions (P50%) in the extracranial vertebral artery (VA), especially the ostium.1,2 Although the absolute risk of posterior circulation ischemic stroke for asymptomatic stenosis remains low,3 the stroke risk increases significantly for symptomatic VA stenosis and reaches 30% at 5 years.4,5 Compelling evidence to determine the optimal therapy for symptomatic VA stenosis is still lacking. Surgical procedures are useful to reconstruct the stenotic lumen but are rarely performed due to perioperative complications.6 The randomized Vertebral Artery Stenting Trial to compare stenting with medical therapy is ongoing.7 So far, medical therapy plus risk factor control remains the mainstay of therapy. For medically refractory stenosis, stenting
⇑ Corresponding author. Tel./fax: +86 21 31161784.
E-mail address: [email protected] (J. Liu). These authors have contributed equally to the work.
0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.04.022
with balloon-expandable stents (BES) enjoys wide popularity due to its high technical success and low complication rate,8,9 but its long-term efficacy remains questionable due to high rates of instent restenosis and stent fracture.10 Self-expanding stents (SES) are designed with high flexibility and enhanced radial expansion force. Thus stenting with SES has the potential of reducing rates of in-stent restenosis and stent fracture. However, available information concerning stenting with SES for vertebral artery ostium (VAO) stenosis is limited. In this study, we present our experiences of stenting with SES to treat symptomatic VAO stenosis in selected patients.
2. Materials and methods 2.1. Study design and patient selection A retrospective study was conducted with patients treated with SES between June 2008 and December 2011 selected from the Interventional Database. Medical records were reviewed to collect data on baseline characteristics including clinical symptoms, risk factors, procedural results, and in-hospital and follow-up out-
Z. Li et al. / Journal of Clinical Neuroscience 21 (2014) 274–277
comes. Angiographic results were reviewed from the picture archiving and communication system (PACS) and Angiography Databank to investigate immediate and follow-up results. This study was approved by the Institutional Review Board at our hospital. The diagnosis of symptomatic VAO stenosis was based on clinical and angiographic evaluation, and was confirmed by two independent neurologists (YWZ and BQD). Clinical symptoms included stroke, transient ischemic attack (TIA), vertigo, ataxia and visual disturbance. Patients were considered suitable to undergo stenting when they met the following inclusion criteria: (1) medically refractory symptoms related to VAO stenosis; and (2) ostial stenosis P70% with at least two risk factors for atherosclerosis. Exclusion criteria were the following: (1) vertebrobasilar infarction associated with diseases of small vessels or perforators or with cardiac embolism; (2) non-atherosclerotic VAO stenosis including dissection, radiation vasculopathy, vasculitis or fibromuscular dysplasia; and (3) allergies to the contrast medium or antiplatelet medication. Informed consent was obtained from each patient before the intervention.
2.2. Stenting procedure All patients received 300 mg aspirin and 75 mg clopidogrel per day for at least 5 days prior to the procedure. All patients received systemic heparin after placement of the sheath. The activated clotting time was maintained at two to three times the baseline throughout the procedure. Routine four-vessel angiography was performed via the femoral route under local anesthesia. Reference VA and subclavian artery (SA) diameters were measured on quantitative angiography. If the reference VA diameter was P4.5 mm and the diameter of reference SA was 610 mm, a SES was considered. An 8 French guiding catheter was positioned into the proximal SA, and a 0.014 inch micro-guidewire was advanced to cross the stenosis under road-mapping. After balloon pre-dilatation, the SES was carefully deployed from the V1 segment to the proximal SA (Fig. 1). Post-dilatation was performed if residual stenosis was >30%. Post-procedural anticoagulant therapy (low molecular heparin, 4000 U, every 12 hours) was administered subcutaneously for 3 days. All patients were maintained on aspirin (300 mg daily) and clopidogrel (75 mg daily) for 6 weeks, followed by aspirin alone (300 mg per day) for 6 months, which was then reduced to 100 mg daily and continued indefinitely.
275
2.3. Follow-up All follow-up observations were performed by two neurologists from our clinical center as a part of usual clinical care (YWZ and BQD). Outpatient clinic follow-up was routinely performed 30 days after the procedure and thereafter at 3 month intervals. New events of vertebrobasilar stroke, TIA, and vascular death were investigated during the follow-up period. Non-invasive imaging (CT angiography, MR angiography, duplex ultrasonography) was coupled with outpatient visits and was scheduled for 30 days and 3, 6 and 12 months after the procedure, and then annually. Digital subtraction angiography was scheduled when restenosis was suspected on non-invasive imaging, or when angiographic evaluation or intervention was performed in other vascular territories. Restenosis was defined as P50% lumen loss observed on follow-up angiography. 2.4. Data analysis All continuous data are expressed as mean ± standard deviation. The range, median, mean, and standard deviation were determined for each measurement. The technical success, restenosis and stent fracture rates of SES placement were compared with our previous results with drug-eluting stents (DES) placement. 3. Results 3.1. Baseline characteristics In total, 32 patients (28 men, four women; mean age 65.6 ± 8.6 years; range, 53–84 years) were included in the investigation. Their clinical characteristics are presented in Table 1. About one third of patients had experienced a previous stroke in the posterior circulation territory, and one third of patients had vertigo. 3.2. Stenotic characteristics The stenosis was located in the right VAO in seven patients and in the left in 25 patients. The degree of stenosis ranged from 70% to 90% (mean, 76.4 ± 6.7). The reference VA diameter ranged from 4.5 mm to 6.4 mm (mean, 5.13 ± 0.79), and the reference SA diameter ranged from 7.5 mm to 10.0 mm (mean, 8.73 ± 0.96). Of the 32 patients, 10 had concomitant stenosis (>50%) or occlusion of the contralateral VA, eight had a hypoplastic contralateral VA, seven had stenosis (>50%) of the ipsilateral SA, and six had occlusion of the unilateral internal carotid artery.
Table 1 Baseline characteristics of patients with symptomatic vertebral artery ostium stenosis
Fig. 1. Schematic drawings of the modified technique of deploying a self-expanding stent in patients with vertebral artery stenosis. The left panel shows the ostial stenosis, and the right panel shows the self-expanding stent being deployed from the V1 segment to the proximal subclavian artery.
Baseline (n = 32) Male:female Mean age (±standard deviation), years
28:4 65.6 ± 8.6
Risk factors Hypertension Diabetes Heavy smoking Alcohol addiction Hyperlipidemia Coronary heart disease
23 (71.9) 9 (28.1) 12 (37.5) 8 (25.0) 10 (31.3) 8 (25.0)
Clinical symptoms Stroke Transient ischemic attack Vertigo Ataxia Visual disturbance
11 (34.4) 3 (9.4) 10 (31.2) 6 (18.8) 2 (6.2)
Data are presented as n (%) unless otherwise stated.
276
Z. Li et al. / Journal of Clinical Neuroscience 21 (2014) 274–277
3.3. Procedural results A modified deployment technique was performed in all patients, which involved deploying the stents from the V1 segment to the proximal portion of the SA (Fig. 2). Technical success was achieved in 32 (100%) patients. In total, 25 (78%) tapered and seven (22%) non-tapered stents were deployed. The tapered stents included Protégé (ev3 Endovascular, Plymouth, MN, USA) and Acculink (Abbott Laboratories, Abbott Park, IL, USA) stents, and the non-tapered stents included Precise (Cordis Endovascular, Bridgewater, NJ, USA), Protégé (ev3 Endovascular) and Acculink (Abbott Laboratories) stents. The specifications of stents used is summarized in Table 2. Post-dilatation was performed in nine (28%) patients. The mean residual stenosis was 11.4% (range, 0–20%). 3.4. Follow-up outcomes The mean duration of clinical follow-up was 18.3 months (range, 3–34 months). No vertebrobasilar stroke, TIA or death occurred during the 30 days after stenting or during the follow-up. One patient developed a TIA related to concomitant internal carotid artery stenosis 11 months after the procedure. We performed carotid angioplasty and stenting for this patient and thereafter TIA did not occur. No ischemic events were observed in the ipsilateral upper extremity. The mean duration of angiographic follow-up was 12.5 months (range, 3–24 months). Digital subtraction angiography was performed in 12 patients, and non-invasive imaging performed in the remaining patients, with CT scans in 20 patients, MR angiography in 10 patients, and duplex ultrasonography in four patients. Restenosis (60%) was observed in one (3.1%) patient 6 months after stenting. In-stent angioplasty or stenting was not performed for this patient because the patient was asymptomatic, and medication and follow-up were continued. No stent fracture was observed. The involved SA lumen covered by the stent mesh remained patent in all patients. 4. Discussion The current study supports the feasibility and efficacy of stenting with SES in selected patients with symptomatic atherosclerotic VAO stenosis. Compared with previous results using DES,11 our
Table 2 Deployed self-expanding stent profiles used for treatment of symptomatic vertebral artery ostium stenosis (n = 32)
Diameter (mm) Length (mm) n à §
Tapered stents
Non-tapered stents
Acculink
Protégéà
Acculink
Precise§
6–8 40 5
7–10 40 10
10 30 1
8 30 1
7–10 40 10
8 40 2
Protégéà 9 30 1
8 30 2
Abbott Laboratories, Abbott Park, IL, USA. ev3 Endovascular, Plymouth, MN, USA. Cordis Endovascular, Bridgewater, NJ, USA.
data suggests that stenting with SES has the same technical success (100%), lower restenosis rate (3.1% versus 5.3%) and fracture rate (0% versus 10.5%). The mid-term follow-up also indicates that it is relatively safe to use our modified deployment technique. For symptomatic VAO stenosis, stenting with BES can be accomplished with complications being rare and the success rate high.5 However, the high long-term restenosis rate, reported to reach 20–48%, remains discouraging.12–15 Many explanations have been proposed for restenosis. VA are arteries with considerable elastic forces and pulsations which have to be counterbalanced by the radial force of a stent. The radial force of BES may be too weak for the mechanical forces of the VA. Different flexibility and contractibility between the stents and vessel wall possibly stimulate chronic inflammation. Lesion length and anatomical characteristics of the artery also influence restenosis.10,16 Compared with BES, DES can reduce restenosis rates by inhibiting neointimal hyperplasia. In our previous cohort of stenting with DES, the restenosis rate decreased to 5.3% after a mean follow-up of 28.3 months, but the stent fracture rate increased significantly.11 Furthermore, the diameter in the majority of DES is less than 5.0 mm, thus ruling out treatment of stenosis if the reference VA diameter >5.0 mm. SES have some advantages for VAO stenosis. SES are designed with more resistance to external forces than BES. The shape memory and chronic radial expansion also enable SES to better comply with pulsations, elastic forces and recoil of rigid plaques. Moreover, there is frequently a fusiform widening of the artery with changing diameters after the ostium stenosis. BES may have a limited apposition in this region. Instead, a SES placed across the VA may appose better to changing vessel diameters. In our series with the
Fig. 2. Self-expanding stent placement in a 60-year-old man with severe stenosis in the left vertebral artery ostium. (A) Digital subtraction angiography showing ostial 90% stenosis of the left vertebral artery, and (B) unsubtracted angiogram showing the morphology of the tapered stent (7–10 mm diameter, 40 mm long) deployed within the vertebral artery and subclavian artery. (C) Subtracted angiogram showing the immediate result without residual stenosis. (D) Subtracted angiogram showing the lumen is well preserved at the 2 year follow-up.
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modified deployment technique, the tapered SES was preferred because it can meet the requirements for the diameter difference between the reference SA and VA. Chung et al.17 reported 20 patients with VAO stenosis treated with SES. None of their patients had recurrent stroke after clinical follow-up of 14.8 months. Five patients had mild intima hyperplasia and no stenosis had a lumen loss >50% after angiographic follow-up of 13.7 months with Doppler ultrasound. Our results are consistent with those of Chung et al., showing the high technical success rate and low restenosis rate of stenting with SES. The restenosis rate (3.1%) in our data is slightly higher than in Chung et al. This may be attributed to the different benchmark for atherosclerosis severity. Most of our patients had concomitant occlusive internal carotid artery diseases or other vascular diseases, indicating that the study population represents more severe atherosclerotic conditions. Different follow-up protocols will also influence the results, caused by the sensitivity and specificity of the follow-up tools. In addition, our study and the one conducted by Chung et al. have a small sample size. Therefore, trials with a large population are warranted to further investigate efficacy. Differing from the traditional deployment technique, we placed the SES from the V1 segment to the proximal SA (Fig. 1). A small protrusion of the deployed stent was usually left in the SA. However, deploying the SES in a short segment of ostial stenosis is challenging. The angulation and tortuosity of the vertebral origin easily prompts the deployed stent to angulate the vessel, and rigid plaque in the ostium can also make the stent leap easily. Stent misplacement and difficulty in retrieving filter protection can be encountered.17 In our series, there was no stent misplacement. We believe that the modified deployment method is more favorable for stent positioning and release than the traditional method. Stents extending from the V1 segment to the SA bridge the two arteries with meshes, acting like a filter. These meshes produce concern regarding possible thromboembolism. In fact, the outward shape of these meshes toward the distal subclavian lumen makes them larger than usual. The mid-term follow-up in our cohort shows that no clinically apparent complication in the dependent upper extremity occurred. This implies that the influence on blood flow by these meshes is possibly minimal. There are some limitations of this study. The study is retrospective in nature, has a small size sample and a limited follow-up period. More data from a large population with long-term follow-up are required to further validate performance. Moreover, patients with reference VA diameter or =50% symptomatic vertebral or basilar artery stenosis: prospective populationbased study. 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Symptomatic ostial vertebral artery stenosis treated with tubular coronary stents: clinical results and restenosis analysis. J Endovasc Ther 2004;11:719–26. 16. Lin YH, Liu YC, Tseng WY, et al. The impact of lesion length on angiographic restenosis after vertebral artery origin stenting. Eur J Vasc Endovasc Surg 2006;32:379–85. 17. Chung SY, Lee DH, Choi JW, et al. Use of self-expanding stents for the treatment of vertebral artery ostial stenosis: a single center experience. Korean J Radiol 2010;11:156–63.
