Subclavian-Vertebral Artery Bifurcation Stenting Using Drug-Eluting Stents: A Report of Two Cases Using Different Techniques

Case Reports

Case 1. A 44-year-old female with a past medical history of neck radiation and chemotherapy for Hodgkin’s disease, bilateral breast cancer and nonischemic cardiomyopathy with an ejection fraction of 35%. She presented with dizziness, left arm numbness and tingling, particularly with arm activity. The left radial pulse was diminished. A duplex scan showed a high-grade stenosis in the proximal left SCA, and angiography showed a high-grade stenosis in the proximal left SCA. The left VA was not visualized. The left internal mammary artery (LIMA) was occluded (Figure 1). The right brachiocephalic artery had no evidence of stenosis. The right VA appeared to be large, but had an 80% ostial stenosis. A decision was made to treat the left-side SCA stenosis with endovascular therapy.
Technique. The patient’s right femoral artery was accessed with a short 6 Fr sheath, and a 6 Fr JR4 diagnostic catheter was used to engage the ostium of the left SCA. The subclavian stenosis was crossed with an exchange-length 0.035 inch Storq^® wire (Cordis Corp., Miami, Florida) with minimal difficulty. The short sheath and JR4 catheter were exchanged for a 7 Fr Arrow^® 65 cm sheath (Arrow International, Inc., Reading, Pennsylvania). Subsequently, predilatation was performed with a 6.0 x 20 mm OptiPro^® balloon (Cordis). This did not result in adequate treatment of the stenosis, and a 6.0 x 29 mm Express™ biliary stent (Boston Scientific Corp., Natick, Massachusetts) was then placed, resulting in excellent expansion of the SCA. However, likely due to plaque shift, the VA not previously visualized was now seen filling antegradely, but with a 90% ostial stenosis. In view of the 80% stenosis of the contralateral vertebral artery and the patient’s symptoms, it was thought reasonable to treat this lesion. Multiple balloon inflations at the VA ostium (crossed through the struts of the SCA stent) gave a suboptimal result, and subsequently a 3.0 x 13 mm Cypher^® stent (Cordis) was placed in the ostium of the vertebral artery through the struts of the subclavian stent using the T-stenting technique. The ostial portion of the stent was then postdilated using a 3.5 x 8 mm Quantum™ Maverick^® balloon (Boston Scientific) up to 16 atm. Final kissing balloon angioplasty was performed. Final angiograms showed a good angiographic result and normal antegrade flow through the vertebral and subclavian arteries (Figure 2). Heparin was used during the procedure, followed by clopidogrel for 3 months and aspirin indefinitely. There were no periprocedural complications. At 1-year follow up, the patient was free of arm symptoms. Her dizziness had improved, but had not totally resolved. There were no neurological sequelae. A duplex scan at 1-year follow up demonstrated good antegrade flow in the VA.

Case 2. A 71-year-old male with a history of coronary artery disease and coronary artery bypass surgery, including a LIMA graft to the left anterior descending artery (LAD), presented with complaints of stable angina and dizziness. Physical examination revealed a diminished left arm pulse and a left subclavian bruit. A duplex scan revealed stenosis at the proximal left SCA with retrograde flow to the left vertebral artery suggestive of subclavian steal syndrome. Angiography showed patent right carotid, right vertebral and left carotid arteries. It also showed a patent LIMA-to-LAD graft; however, there was subtotal occlusion in the left SCA proximal to the origin of the LIMA and at the origin of the VA, with 80% stenosis of the ostium of the left VA (Figure 3). Endovascular treatment of the subclavian artery for LIMA graft preservation was chosen. Because of the heavy plaque burden in the SCA stenosis right at the ostium of the VA (with an 80% ostial stenosis), there was significant risk of acute closure of the VA during SCA stenting. Thus, we elected to perform bifurcation stent implantation using the crush-stenting technique (usually used in the coronary arteries), which would enable us to protect the VA without the risk of not being able to recross after SCA stent placement.
Technique. A 6 Fr JR4 diagnostic catheter was used to access the left SCA and an exchange-length Storq wire was passed through the subtotal occlusion in the left SCA. The JR4 catheter was exchanged for a 7 Fr 65 cm Arrow sheath. A 0.014 EZ FilterWire™ (Boston Scientific) was advanced through the stenosis and placed in the distal cervical segment of the VA. Kissing balloon angioplasty was then performed with a 2.5 x 15.0 mm Maverick balloon in the vertebral artery and a PowerFlex^® 6.0 x 2.0 cm balloon (Cordis) in the SCA (Figure 4). A Cypher 3.5 x 13.0 mm stent was advanced in the proximal portion of the vertebral artery with some of the stent hanging in the subclavian, and a Genesis 8.0 x 24.0 mm stent (Cordis) was placed across the subclavian stenosis, making sure that it remained proximal to the origin of the LIMA. The Cypher stent was then deployed at 12 atm and the filter basket was captured and retrieved. Next, the Genesis stent was deployed at 8 atm, thereby crushing the previously deployed Cypher stent. A 0.014 Choice Floppy^® wire (Boston Scientific) was used to recross into the Cypher stent through the struts of the deployed Genesis stent and the crushed Cypher stent. The struts of the crushed Cypher were sequentially dilated using a 1.5 and a 2.5 mmHg Maverick balloon. Subsequently, kissing balloon angioplasty was performed using a Quantum 3.5 x 12.0 mm balloon in the Cypher, and an Optipro 8.0 x 2.0 mm balloon in the subclavian stent. Final angiograms showed excellent flow through the vertebral and subclavian stents, with no residual stenosis in either stent. There was also brisk antegrade flow in the LIMA graft. Heparin was used for procedural anticoagulation. The patient was prescribed clopidogrel for 6 months and aspirin indefinitely. There were no procedural complications. At 18-month clinical follow up the patient reported complete resolution of angina. His dizziness did not diminish, however. A duplex scan 1 year after the procedure showed good antegrade flow through the VA and SCA.

Discussion

VA disease is an important cause of ischemic strokes in the posterior circulation.^9,10 Although VA disease is often asymptomatic, 50% of patients present initially with stroke, and 26% with a transient ischemic attack (TIA) followed rapidly by stroke. For patients experiencing vertebrobasilar ischemic (VBI) TIAs, VA stenosis portends a 20–30% risk of stroke over 5 years.^11,12 Dizziness, though very commonly experienced, is rarely present alone, and is a nonspecific symptom. Dizziness alone is not an independent indication for VA stenting. The true hallmark of VBI is the simultaneous manifestation of multiple symptoms, the most common of which are vertigo, visual dysfunction, peri-oral paresthesia and so forth.¹³ Current recommendations are to intervene in cases of VA stenosis in patients with posterior circulation stroke or definite symptoms of VBI. For asymptomatic patients, there is a less aggressive recommendation for intervention in cases of significant unilateral stenosis in a dominant VA or one that is associated with ipsilateral carotid occlusion or tight stenosis of contralateral VA.^6,14
VA stenosis may cause symptomatic vertebrobasilar ischemia by three mechanisms: embolic, thrombotic (thrombus formation over an existing stenosis) or low-flow hemodynamic mechanism.^14,15 The latter requires the presence of an incomplete circle of Willis or a contralateral nondominant or stenosed VA. However, embolic or thrombotic strokes may happen even with a normal contralateral VA. Unlike carotid artery disease, where large randomized trials have assessed the benefit of surgical/percutaneous therapy for asymptomatic carotid stenosis versus medical therapy, no randomized study has been done on vertebral artery disease.
None of our two cases fit in the above indications for VA stenting. However, these cases represent a clinical scenario that has scarcely been described in the literature, where the primary indication for intervention is SCA ischemia and the VA is being stented to protect against closure during SCA stenting. The literature is silent on the effect of acute iatrogenic closure of VA. In view of the absence of this knowledge, we elected to protect the VA, even in patients with no definite symptoms of VBI.
A 4-vessel intracranial angiogram prior to any intervention in the carotid or vertebral arteries has been recommended. In the case of VA stenting, this can define the posterior circulation and the contralateral side, the integrity of the circle of Willis and also any collateral that may be supplying the territory. It also helps to identify any branches that may be cut off in the event of procedural embolization. In our two cases, we did not perform 4-vessel intracranial angiograms, as both cases were started as SCA stenting procedures, and vertebral artery stenting was performed in an ad hoc fashion to protect VA closure with SCA stenting.
While VA stenting may not be indicated in most cases of SA stenting, in certain patients such as those presented here, due to the proximity of the VA to the SA stenosis and due to the tight stenosis of the VA ostium, there is a risk of compromising vertebral flow, thus bifurcation techniques may be required to preserve flow through the VA. Bifurcation stenting techniques have been well described in coronary artery stenosis,¹⁶ but rarely described in cases of supra-aortic vessel angioplasty procedures.^7,17 Since bifurcation stenting techniques have a higher rate of restenosis in the coronary arteries,^18,19 more recently, drug-eluting stents have been used with significantly lower restenosis rates.²⁰ Due to the paucity of reported literature, the risk of restenosis for bifurcation stenting in the vertebral-subclavian area is not known. In plain vertebral stenting, the reported restenosis rates are anywhere from 10% at 6 months to 25–43% at 1 year.^1,21–23 However, these are likely to be higher with bifurcation stenting, as is seen in coronary artery. We therefore elected to place sirolimus-eluting stents in the vertebral arteries using bifurcation stent techniques and have documented patency up to 1year in our 2 patients. Other preliminary data exist regarding the safety and feasibility of drug-eluting stents in extra- and intracranial vessels.^2,24 More data are needed to determine if these results are also seen in larger patient series with longer follow-up periods. This is the first report of crush-stenting with drug-eluting stents in the vertebral-subclavian region, and offers preliminary data for the feasibility and long-term success of this approach.
There are no evidence-based guidelines for follow up of patients after VA stenting for detection of restenosis. Furthermore, there is no consistent relationship between angiographic restenosis and symptoms or outcomes. Albuquerque et al reported angiographic follow up in 30 of 33 patients after VA interventions with a mean follow up of 16.2 months. Angiographic restenosis occurred in 43% of the patients, but they found no correlation with restenosis and recurrence of symptoms. It is our practice to perform clinical follow up in our patients at 1, 6 and 12 months, and yearly thereafter. Duplex sonography to document antegrade vertebral flow is performed at 1-year follow up. Angiography is performed in patients who develop symptoms of VBI. Antiplatelet therapy with aspirin is recommended lifelong, but clopidogrel is generally discontinued 1 month after placement of bare-metal stents. However, with drug-eluting stents the recommended duration is 3–6 months for coronary lesions (depending on the stent type). However, this may have to be continued for a longer duration, especially in view of recent reports of late stent thrombosis.^25–27 Another issue of importance is the use of distal embolic protection in this setting. Unlike saphenous vein graft interventions^28–30 and carotid artery interventions^31–34 where strong data support the clinical benefit of embolic protection, for VA, there is a paucity of such data. There are, however, studies that demonstrate the occurrence of distal embolization during vertebral artery stent placement. Sawada et al studied 12 consecutive patients undergoing percutaneous intervention for SCA and VA stenosis.³⁵ Using transcranial Doppler, they found that while no embolic signals were seen pre-angioplasty in any patient, several signals were detected immediately after angioplasty in 6 of the 12 patients. These signals were detected despite the routine use of heparin and antiplatelet agents. Canyigit et al studied 16 patients pre- and post-VA stenting using diffusion-weighted magnetic resonance imaging.³⁶ They found that 6 of 16 patients had a total of 25 new lesions in the vertebrobasilar circulation area in the post-stent images. All of these patients were asymptomatic. These authors thus showed that there is a significant risk of asymptomatic embolism with VA stenting. In view of these data, we think that embolic protection should be standard in all patients undergoing VA stent placement. Its feasibility was shown in a study of 12 patients who underwent VA stenting using the FilterWire embolic protection device.²⁴ They were able to successfully place this device in 11 patients and retrieved macroscopic debris in 8 of the baskets. We used a distal protection basket in our second case (crush-stenting case), but not in the first case. In the first case, since the vertebral artery was stented through the struts of the previously deployed SCA stent, we were concerned about the ability of the filter delivery catheter to traverse through the struts of the SCA stent, and also about whether the retrieval sheath would cross the struts. These technical difficulties, especially in basket retrieval through stent struts, have been previously reported.²⁴ However, with the availability of newer-generation embolic protection devices (such as the SpiderRx^® filter device; ev3, Inc., Plymouth, Minnesota) that are simpler to navigate, this may become technically easier.
In conclusion, we have described two patients with complex subclavian-vertebral stenosis (with symptoms of SCA ischemia) who we treated with concomitant vertebral artery stenting using bifurcation stenting techniques in order to prevent closure of the vertebral artery. Large randomized studies or a multicenter registry are needed to address the issues raised by this report.

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