Percutaneous transluminal angioplasty and stenting of the vertebral artery ostium with balloon-mounted bare coronary stents
Correspondence Address: Source of Support: Kowsar Research Committee and the
research council of Shiraz University of Medical Sciences, Conflict of Interest: None DOI: 10.4103/0028-3886.82748
Source of Support: Kowsar Research Committee and the research council of Shiraz University of Medical Sciences, Conflict of Interest: None
Background : Vertebral artery ostial stenosis (VAOS) is one of the most frequent causes of posterior circulation stroke. Percutaneous angioplasty and stenting (PTAS) is one of the treatment modalities. Patients and Methods : This is a longitudinal observational study from September 2006 to February 2009, conducted at hospitals affiliated with the Shiraz University of Medical Sciences, Shiraz, southern Iran. The patient cohort included patients with posterior circulation stroke or transient ischemic attack (TIA) and more than 70% VAOS, and patients with asymptomatic VAOS of more than 70% and aplasia or total occlusion of the contralateral VA or subclavian artery. All the patients underwent PTAS with balloon-mounted bare coronary stents. Technical success, procedural complications, composite outcomes of death, stroke or TIA in the vertebrobasilar territory during the first 30 days, stroke or TIA in the vertebrobasilar territory, and restenosis during follow-up, were assessed. Results : During the study period, 81 patients (mean age 68 + 8.9 years, 63 (78%) males, 71 symptomatic and 18 asymptomatic) underwent the procedure. Technical success was achieved in 88 (99%) patients. Procedure-related complications, other than puncture site complications, were seen in two patients (2.2%). The composite outcome of death, stroke or TIA in the vertebrobasilar territory during the first 30 days was 1%. None of the patients had clinical recurrence or restenosis during the follow-up (mean follow-up 14 months). Conclusion : Percutaneous transluminal angioplasty and stenting of the proximal VA was feasible and safe. The risk of restenosis should be analyzed in long-term studies with angiographic follow-up.
Keywords: Angioplasty, balloon angioplasty, origin, ostium, stenosis, stent, vertebral artery
Vertebral artery ostium is considered to be the most common site for posterior circulation atherosclerotic lesions. In the New England Posterior Circulation Registry, 20% of the patients were found to have vertebral artery ostial stenosis (VAOS).  Proximal vertebral stenosis may predispose to posterior circulation stroke due to artery-to-artery embolism or impaired hemodynamics.  Symptomatic vertebrobasilar disease refractory to medical treatment is associated with 5 to 11% risk of stroke or death at one year.  Surgical revascularization procedures are associated with good long-term outcomes, however, these procedures are associated with a relatively high rate of morbidity: recurrent laryngeal nerve palsy, Horner's syndrome, lymphocele, chylothorax, pneumothorax, and fistula formation.  Percutaneous transluminal angioplasty and stenting (PTAS) have been used since the 1980s to treat symptomatic severe VAOS.  Although the periprocedural outcomes are relatively satisfactory, restenosis has been a major concern. Here we report the periprocedural and medium-term outcomes in patients treated for VAOS with PTAS.
The study was conducted at the Namazi, Faghihi, and Kowsar Hospitals, affiliated to the Shiraz University of Medical Sciences in Shiraz, southern Iran, from September 2006 to February 2009. This university hospital complex is a high-volume center for cardiac  and cerebrovascular interventional procedures  and a referral center for patients from southern Iran. Inclusion criteria for PTAS were: patients aged > 18 years, with ischemic stroke or transient ischemic attack (TIA) in the verebrobasilar artery territory, with > 70% vertebral artery (VA) stenosis. Asymptomatic patients with aplasia or total occlusion of the contralateral VA or subclavian artery and >70% stenosis were also recruited. Severity of the stenosis was calculated according to the North American Symptomatic Carotid Endarterectomy (NASCET) criteria. 
Exclusion criteria were terminal disease with life expectancy of less than three years, history of anaphylactoid reaction to non-ionic contrast agents, refusal by patients, and severe stroke. The study was approved by the Ethics Committee of the Shiraz University of Medical Sciences. The possible outcomes and non-approval of the procedure for this indication by the Food and Drug Administration (FDA) were explained to all participants and a written informed consent was obtained.
All patients were pre-treated at least for one week with clopidogrel 75 mg / day and acetylsalicylic acid 80 mg / day. For urgent procedures, patients received a loading dose of 300 mg clopidogrel and 325 mg acetylsalicylic acid on the day of the procedure. All patients were heparinized with a 7500 - 10 000 IU intravenous bolus of heparin prior to the procedure. We did not use a pressurized heparin infusion system. After femoral arterial puncture a 6-F right Judkins guide catheter was advanced over a 0.035-inch hydrophilic wire to a stable position in the subclavian artery and then a 0.014 guide wire was passed through the stenotic lesion. Pre-stent angioplasty was not needed in any of the patients. Low-profile, balloon-mounted coronary stents were navigated successfully through the tight stenosis. The balloon-mounted coronary stents deployed were Vision (Guidant Corporation, Indianapolis, IN, USA), Tsunami Gold (Terumo, Tokyo, Japan), and Skylor (Invatec, Brescia, Italy) devices. Stents were deployed in such a manner that the proximal end of the stent extended a few millimeters into the lumen of the subclavian artery, covering the whole lesion, and at least 3 mm into the normal distal VA. Post-stent angioplasty was done with balloons smaller than the diameter of the vessel. Distal protection devices were not used. The patients were admitted to the Intensive Care Unit for one day and then discharged. The patients were put on clopidogrel 75 mg / day for at least three months and acetylsalicylic acid 80 mg / day indefinitely.
Technical success was defined as < 20% residual stenosis by angiography after stent placement. All patients were followed by a neurologist and a cardiologist every two weeks during the first postoperative month, every four weeks during months two to six, and every three months thereafter. The patients were instructed to report to the Neurology Emergency Department if they presented any neurological symptoms attributable to the vertebrobasilar territory.
The primary outcomes were: (1) composite outcome of death, stroke or TIA in the vertebrobasilar territory within 30 days of the procedure and (2) stroke or TIA in the vertebrobasilar territory any time during the follow-up. Another outcome measure was the restenosis rate one year post procedure. For this subgroup of patients, a duplex ultrasound examination of the neck arteries was performed at 6 and 12 months and contrast-enhanced magnetic resonance angiography (MRA) of the neck region 12 months later. Criteria for restenosis included: intrastenotic peak systolic velocity ≥ 120 cm/s, intrastenotic and poststenotic blood flow abnormalities, increased pulsatility in the prestenotic area, and diameter reduction in the B-scan.  For patients with suspected restenosis (more than 50% according to the NASCET criteria) angiography was recommended.
During the study period 81 patients (mean age 68 ± 8.9 years, 63 males) underwent the procedure. Vascular risk factors included: diabetes mellitus in 21 (23.5%), hypertension in 66 (74%), hyperlipidemia in 43 (48%), and smoking in 34 (38%). Seventy-one patients (79.8%) were symptomatic with stroke or TIA, attributable to VAOS, and 18 patients were asymptomatic with > 70% VAOS and aplasia or total occlusion of the contralateral VA or subclavian artery, found during the diagnostic evaluation for carotid disease or before cardiac surgery.
Technical success was achieved in 80 (99%) patients. The degree of stenosis post procedure was less than 5% in all the patients. Procedure-related complications included dissection (two patients, 2.2%) and puncture site complications (five patients, 5.6%). No cases of perforation, stent migration, arteritis or hyperperfusion syndrome were seen. The composite outcome of death, stroke or TIA in the vertebrobasilar territory within the first 30 days was seen in one patient (1%), who died of vertebrobasilar stroke. No cases of myocardial infarction or peripheral vascular disease were seen during the first 30 days after the procedure.
One patient died three weeks following the procedure. The patient had a long history of hypertension and diabetes mellitus and presented with recurrent attacks of vertigo and fainting, despite antiplatelet and statin therapy. Cardiac causes of syncope were excluded. Cerebral angiographic examination revealed 80% stenosis of the right internal carotid artery, 90% stenosis of the left V1 segment, and 70% stenosis of the left V4 segment. Angioplasty and stenting of the left V1 artery were successfully performed. In the same session stenting of the V4 area was also attempted. The patient developed brainstem and occipital manifestations within 24 hours, and imaging studies revealed a large infarction in the territory of both the posterior cerebral arteries. The mean follow-up period was 140 months. Eight patients (8.9%) were lost to follow-up. None of the remaining patients had recurrence of stroke or vertebrobasilar territory. For the first 19 (21.3%) patients in the study sample, ultrasound and MRA examinations were performed during follow-up. As no significant restenosis (> 50%) was detected by duplex ultrasound or MRA, no follow-up angiographic studies were done.
Stroke is a major health concern in Iran and the reported incidence of stroke, particularly ischemic stroke, is significantly higher when compared to most Western countries.  In a hospital-based study conducted in central Iran, one-month case fatality was higher than in European countries.  Endovascular treatments may be good therapeutic options for both primary and secondary prevention of ischemic strokes.
In line with our previous reports of endovascular treatments of Iranian patients with cerebrovascular diseases , we report here our results with PTAS with balloon-mounted bare coronary stents for VAOS in a high-volume center in southern Iran. We had a good rate of technical success and few adverse procedural outcomes (mostly dissection). Mortality and morbidity in our series was 1.1%, a figure reflecting the death of only 1 patient due to vertebrobasilar infarction during V4 angioplasty. Strictly speaking, this death cannot be attributed to VAOS. On the basis of this experience, we conducted staged PTAS (first in extracranial and then in intracranial vertebral arteries) for all subsequent patients. We did not encounter complications such as stent fracture  or hyperperfusion syndrome  reported by other investigators. The rate of radiological restenosis and clinical recurrence was low in our study sample.
Vertebral artery ostial stenosis accounts for about one-third of all cases of vertebrobasilar stroke. , In recent times, the therapeutic approach to these lesions has been shifted from surgical to endovascular intervention due to difficulties with access and the relatively high rate of morbidity associated with surgical procedures. Percutaneous transluminal angioplasty without stenting in VOAS is associated with high restenosis rates. , At present, PTAS is the most common endovascular intervention for the treatment of VAOS. Only one randomized clinical trial has been published on the treatment for extracranial vertebral stenosis. In the subgroup of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) trial, 16 patients with severe symptomatic VA stenosis were randomized to endovascular treatment (eight patients) or medical treatment alone (eight patients). None of the patients, in either group, had composite outcome of death or stroke within the first 30 days. No patients in either group had ischemic events in the vertebrobasilar territory during the follow-up period of approximately five years. 
The feasibility and safety of PTAS for vertebral arteries was previously shown in the case series, but the issue of restenosis has remained unsolved. A technical success rate of nearly 100% has been reported in all the published case series. ,,,, The procedure-related complication rates other than access site complications, periprocedural mortality and morbidity attributable to the procedure were between 0 - 4.2% and 0 -.5%, respectively. ,,,, In spite of the consistency in the feasibility and safety of the procedure, the issue of efficacy remains controversial, with opinions ranging from 'effective'  to 'dubious'.  In most of the series, the follow-up included clinical assessment or assessment by duplex ultrasound. In the series using follow-up angiography, a six-month post procedure, restenosis of ≥ 50% was reported in 8.5 to 43.3% of the patients. ,,,
Incidental cases of asymptomatic vertebral stenosis may be detected during the evaluation of carotid disease. As is the case for symptomatic V1 stenosis, there is no common policy for the treatment of these patients. We considered PTAS only for asymptomatic patients with > 70% VAOS and aplasia or total occlusion of the contralateral VA or subclavian artery. Other studies considered PTAS for asymptomatic patients with impaired contralateral, vertebral  or anterior circulation, as indications for treatment. 
The most important shortcomings of our study were the short period of follow-up and the lack of angiographic follow-up. For stenosis greater than 50%, the specificities for contrast-enhanced MRA and color duplex ultrasound were 94.8 and 97.7%, respectively, in a pooled analysis,  although some investigators expressed skepticism about these figures.  The low rate of restenosis and recurrence of stroke in our study, which is at variance with previous studies, may be related to our methodological shortcomings and relatively short duration of follow-up, respectively. Restenosis is a major unresolved issue in the stenting of VAOS. ,,, Of l;ate, drug-eluting stents have been advocated to reduce the rate of restenosis. 
This research was supported by the Kowsar Research Committee and the research council of Shiraz University of Medical Sciences. We thank K. Shashok (Author AID in the Eastern Mediterranean) for improving the English in the manuscript.