Safety Aspects in Carotid Artery Stenting - Is Flow Reversal the Solution?

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Citation
ICR 2007;2007:2(1):42-44
DOI
http://dx.doi.org/10.15420/icr.2007.42

Since the publication of the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) and Stent-supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE) studies, doubts have been raised regarding the safety of carotid artery stenting (CAS) as an alternative carotid intervention to carotid endarterectomy (CEA). A recent meta-analysis1 recommended the cautious use of CAS, and concluded that CAS for low-operative-risk patients should be subjected to randomised controlled trials. It might be said that the once optimistic view of CAS has softened, and has been replaced by a healthy scepticism. This accepted, it is clear that CAS is preferable when the patient is deemed to be at high surgical risk and, as meaningful subset analyses emerge from the ongoing trials, it is likely that some patients will respond well to CEA and some with CAS, and the remainder should be equally well treated by either.
The purpose of this article is to try to put forward the author’s view on cerebral protection during CAS, and to highlight Södersjukhuset’s experience with the flow reversal system, Gore Neuro Protection System (NPS) (WL Gore, Flagstaff, Arizona).
Before embolic risk and the reduction of this risk by the deployment of cerebral protection systems are discussed, we must remember that embolic risk is not the only source of procedural neurological hazard. There are, of course, numerous other causes of procedural stroke, including haemodynamic injury, acute carotid occlusions and the uncommon contrast encephalopathy.2 Discussion of these is beyond the scope of this article.

Can Vulnerable Plaque Be Identified Prior to Intervention?

Biasi et al.3 described the importance of plaque characteristics in determining outcome after CAS. The term greyscale median (GSM) describes an objective parameter of plaque echolucency, and a GSM score <25 predicts a worse outcome than for the group of patients with a GSM score >25. The only other predictor of a worse outcome is the degree of stenosis: the tighter the stenosis, the higher the risk. Of course, the stenosis measurement is simply a surrogate marker of emboligenic risk. Other authors have not reproduced these findings,4 and there is disagreement about the importance of plaque echolucency in identifying patients at risk of peri-procedural neurological events.

The Influence of Patient Anatomy on Outcome

Tortuous or variant anatomy can increase both the technical complexity of CAS (leading to increased procedural stroke) and the technical failure rate.5 It is crucial to know the anatomical challenges of a case for planning purposes, and this usually mandates ‘overview’ imaging such as magnetic resonance angiography (MRA), computed tomography angiography (CTA) or catheter arch aortography. Patients should be graded according to their anatomical complexity and chosen in a way that suits the experience of the physician performing the CAS procedure.

Neuroprotection During Carotid Artery Stenting

Do we need to protect the brain during CAS? We do not know for certain. There is no first-class evidence that supports the theory that patients undergoing protected CAS do better than those undergoing unprotected CAS. What we know is that debris is released from the atherosclerotic plaque during manipulation with guidewires, filters, stent deployment and even lesion crossing, pre- and post-dilatation, with a filter and filter deployment and retrieval stages. Moreover, catheter manipulation in the aortic arch and selective catheterisation of the supra-aortic vessel, a prerequisite for CAS from a femoral or brachial approach, is emboligenic. We also know that up to eight times more microembolic signals are detected during unprotected carotid angioplasty than during CEA on procedural transcranial Doppler (TCD).6 More recent work on new white lesions detected with diffusionweighted magnetic resonance imaging (MRI) confirms the higher microembolic load in filter-protected CAS compared with CEA.7 Kastrup et al.8 performed a systematic review of 839 patients treated with protected CAS (largely of the filter type) and 2,357 without protection. This indicated that cerebral protection significantly reduced embolic complications (1.8% in the protected group versus 5.5% in the unprotected population), although many of the studies included employed historical controls and were self-audited and of small sample size. There are no randomised trials to guide us. However, it is clear that all available protection systems can and do trap macroemboli that would otherwise pose a significant threat of major stroke. A recent study highlights that in 279 patients treated with filter-protected CAS, visible debris was found in 169 filters (60%).9 Therefore, it would seem wise to use some kind of cerebral protection device (CPD), analogous to the use of a parachute when skydiving. A randomised trial is not necessary to prove a parachute’s value under these circumstances.

Since 1990, when Théron et al.10 first described cerebral protection during CAS using an occlusion balloon to avoid distal embolisation, a number of dedicated devices have been developed. Thanks to new materials and technical improvements, we now have a range of products that can be used in order to protect the brain from macro-and microembolism during CAS.
Products available operate in different ways, and can be grouped in order of how they work, i.e. distal filters, distal balloon occlusion, proximal balloon occlusion and flow reversal. The remainder of this article will focus on filters, balloon occlusion systems (proximal and distal) and flow reversal.

Filters

Filters are the most frequently used type of CPD. These are easy to use and the pore size varies between 60 and 140 microns. There are two main designs: a basket of Nitinol mesh (e.g. SpideRx™ filter, ev3, Inc., Plymouth, Minnesota), or a perforated polyurethane membrane (e.g. FilterWire EZ, Boston Scientific, Natick, Massachusetts). Filters allow constant perfusion of the brain, which could be important in patients with hypoperfusion syndrome or in patients with an incomplete circle of Willis. Particles smaller than the pore size probably pass unhindered to the brain, and some may pass beside the filter in case of poor wall apposition. In order to establish protection using a filter, the undeployed filter has to cross the lesion while flow in the internal carotid artery is antegrade. This is clearly an unprotected and potentially emboligenic stage of the procedure. However, these devices, like every other protection system, are capable of trapping macroemboli.
There are trade-offs. There is potential for intimal damage in the distal internal carotid artery (ICA) caused by the filter.11 If the ICA above the lesion is tortuous, there might not be enough ‘landing zone’ for safe placement of the filter.

Distal and Proximal Ballon Occlusion

These devices create a no-flow situation in the ICA beyond the treated segment, and it must be remembered to aspirate debris after completion of procedural steps. One example of distal balloon occlusion is the PercuSurge GuardWire (Medtronic, Santa Rosa, California). The MO.MA device, (Invatec, Roncadelle, Italy) effects proximal balloon occlusion of the common and external carotid arteries (CCA and ECA).

The ECA balloon in this system is fixed to the sheath at a pre-determined length, and delivery of guidewires and stents is performed through a sidehole of the sheath. Schmidt et al.12 compared the MO.MA device with the EPI Filterwire (Boston Scientific Corp., Santa Clara, California). Microembolic signals (MES) were monitored during five stages of the CAS procedure (see Figure 1):
• placement of the protection device; • passage of the stenosis; • stent deployment; • balloon dilatation; and • retrieval of the protection device.
The authors reported a significant reduction (but not an abolition) of MES counts during phases II–IV, and in total when using the MO.MA device. It is difficult to explain the presence of any MES in the MO.MA group. After all, there ought to be flow arrest once ‘protection’ is established. Perhaps movements of the occlusion balloon in the CCA and ECA can liberate small particles through microintimal damage? The other potential explanation is misalignment of the ECA balloon, which is mounted at a fixed distance from the end of the sheath.

Flow Reversal

The Parodi antiembolism system (PAES) (Arteria Medical Science, Inc., San Francisco, California) has been modified after Juan Parodi’s original design. The only device available that effects constant passive procedural flow reversal is the Gore NPS. The system achieves reversed flow by means of occluding the CCA and ECA with elastomeric balloons. The system is connected to the contralateral femoral vein via the Gore External Filter, creating an arteriovenous shunt. Therefore, blood passes from the contralateral cerebral circulation across the circle of Willis, down the ICA to be treated (by reversed flow), and into the low-pressure femoral vein (see Figure 2).

In a seven-centre, non-randomised prospective trial, Adami et al.13 treated 28 out of 30 patients using PAES. Flow reversal was not tolerated, presumably because of inadequacies of the circle of Willis and/or significant disease of the contralateral ICA in the remaining two patients. TCD monitoring in all patients demonstrated a complete absence of MES during the procedures (see Figure 3).
As yet there are no data available on the efficacy of the Gore NPS. However, a post-marketing study is planned in the US and Europe to assess procedural safety, namely the Embolic Protection with flow Reversal study.

Södersjukhuset’s Experience with Flow Reversal

At Södersjukhuset in Stockholm, CAS has been performed since late 2004. In common with most other centres worldwide, the CPD of choice has been filters. Our filters of choice have been the SpideRx/FX, because this system enables the operator to cross the lesion with his/her preferred wire. Our second CPD is the FilterWire EZ. When the Gore NPS became available, the decision was made within the team, comprising interventional radiologists and vascular surgeons, to trial the device in our routine clinical practice because we approved of the concept. We have utilised flow reversal in 12 cases, although one patient did not tolerate it. The remaining 11 patients tolerated the system well and had good outcomes from CAS. We are fortunate in having had access to the refined system and support from WL Gore, Scandinavia. Consequently, it would appear that, although modest, our experience is in fact one of the largest experiences of the modified system to date.
At first, this system appears cumbersome, but after a few cases this rapidly becomes irrelevant. We have found that the procedure time is comparable with filter-protected cases, and so far we have not had any adverse events. At our institution we do not have access to TCD and thus we have not been able to critically evaluate the system in a systematic way regarding MES.
There are obvious advantages of this system compared with filters:14
• lesion-crossing is protected; • there is no need for either a distal landing zone or a ‘mechanical’ device in the distal ICA; • microbubbles in the stent delivery system can be aspirated; and • vulnerable lesions with thrombus may be treated.

The disadvantages of the Gore NPS is the large profile sheath that is compatible with 9 French (Fr), which clearly requires the use of a closure device. This has to be offset against the fact that a filter-protected CAS procedure requires only a 6Fr sheath. There is undoubtedly a learning curve when using the system. The rate of intolerance to flow reversal is around 5%, and this would suggest that other CPDs should be available. The importance of a low origin of the superior thyroid and/or ascending pharyngeal artery is yet to be determined. In our experience, this does not seem to influence the achievement of flow reversal. The possibility of vessel wall damage caused by the occlusion balloons has to be considered and it is important not to overinflate the balloons, although these are compliant elastomeric balloons that are formulated for use against delicate intima.

Summary

CAS and CEA are procedures that have prophylactic intent, i.e. they should prevent subsequent stroke and stroke death. However, any potential benefit of these interventions has to be weighed against procedural risk of stroke. We have two methods that complement each other, but to date only CEA has been proved to be both efficient and safe.
It must be borne in mind that there are no embolic protection devices on the market today that protect the brain from the manipulations needed to gain access to the supra-aortic vessels, and hence there is no such thing as ‘total protection’.
Our view of the Gore NPS from a strict ‘user perspective’ is optimistic, and we believe that it could have significant advantages over other protection devices. It would seem to control not only procedural macroembolisation, but also microembolisation. There are additional factors that are important in keeping complication rates low, including careful patient selection, optimised medical treatment and meticulous technique.
The surgical and endovascular community (both interventional radiology and cardiology) should join forces in an attempt to establish the relative roles of CAS and CEA in the future. As Professor Naylor stated: “CEA and CAS will inevitably have a complementary role. It is therefore imperative that we support the two remaining trials that are randomising recently symptomatic patients, the International Carotid Stenting Study (ICSS) in Europe and Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) in North America.”15 Ôûá

Acknowledgements

Thank you to Dr Sumaira Macdonald for her guidance.

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