Use of cerebral protection during carotid artery stenting

Bernhard Reimers
Cardiology Department, Mirano Hospital, Mirano, Italy

Address for correspondence:
Dr Bernhard Reimers
Cardiology Department
Mirano Hospital
Via Mariutto 13, 30035 Mirano, Italy
Tel: +39-(041)-579-4261
Fax: +39-(041)-579-4309
Email: ulss13mir.card@tin.it


Abstract
Carotid artery stenting (CAS) is emerging as a less invasive alternative to carotid endarterectomy, although embolic neurological events occur invariably during CAS. These are often attributable to fragments of atheromatous plaque dislodged during the stenting procedure. Use of a protection device can minimise this risk, and three approaches have been developed: distal occlusive balloons, distal filters and proximal protection by occlusion of common and external carotid arteries. Distal protection devices must cross the lesion for correct positioning and therefore carry a risk of causing embolisation in the absence of cerebral protection. In contrast, proximal systems provide cerebral protection before any device passes the lesion and therefore should enable complete prevention of embolisation. Despite the lack of randomised trials evaluating these devices, available data indicate superiority of protected over unprotected CAS. The capture of debris and prevention of emboli, few device-related complications and technological improvements in newer devices support the use of cerebral protection for CAS.

Introduction
CAS is emerging as an alternative therapy to surgical carotid endarterectomy (CEA) for the treatment of extracranial carotid stenosis [1-3]. The common goal of both procedures is the prevention of stroke and the efficacy of the procedure depends on the periprocedural complication rates. The endovascular stent procedure offers a less invasive approach to achieve this goal by avoiding some of the perioperative complications of surgical treatment. The randomised trial of carotid angioplasty (the Carotid and Vertebral Artery Transluminal Angioplasty Study - CAVATAS) showed that despite the use of sub-optimal interventional techniques the early and 3-year outcomes of endovascular treatment or carotid surgery were equivalent [2].

Despite the routine application of stents, advanced stenting techniques, and combined antiplatelet therapy with aspirin plus clopidogrel or ticlopidine, embolic neurological events occur invariably during CAS. Obstructive carotid artery lesions are known to contain friable, ulcerated and thrombotic material [4] that can embolise during the intervention as shown in transcranial Doppler, ex vivo [5] and in vivo [6] studies.

Figure 1
Figure 1. Angiographic images of a tight, calcific stenosis of the proximal internal carotid artery before (a) and after (b) stent implantation. (c) The protection device removed following the procedure.
It has also been shown that microembolisation occurs considerably more frequently during CAS than CEA [7]. In order to minimise the risk of embolic neurological events, a number of protection strategies have been introduced into the carotid stenting procedure. A reduction of the Doppler-defined embolic load by means of a protection device has been demonstrated [8]. Preliminary results indicate that the refinement of stenting techniques, the increasing experience of the physician, and the routine use of cerebral protection produce results with CAS similar to the best surgical series (Figure 1) [3,9,10].

Figure 2
Figure 2. The three different concepts of cerebral protection applied during carotid artery stenting.
The first system, a balloon for distal occlusion, was developed and used by Theron in 1990 [11]. In current practice, three different approaches are used for cerebral protection (Figure 2): two systems of distal protection (distal occlusive balloons and filters), and proximal protection using the occlusion of the common and external carotid arteries. The histopathological analysis of the debris collected using the various systems of protection has demonstrated that this debris comprises fragments of atheromatous plaque dislodged during carotid stenting [6]. In this article, the three different approaches to cerebral protection are briefly described.

Distal occlusive balloons
Distal occlusive balloons constitute the first system of protection used on a large scale.8 They consist of a guide of 0.014 inches with a balloon on the distal portion that may be inflated and deflated through a very small channel contained in the guide itself (PercuSurge™/GuardWire™). The lesion is crossed with the guide thereby positioning the balloon distally to the stenosis where it is inflated until the blood flow in the internal carotid artery is blocked. Following this, the angioplasty and stenting procedure is carried out. On completion of the procedure, a catheter is advanced up to the distal balloon and the column of blood contained in the occluded internal carotid artery is aspirated. In this way debris dislodged incidentally during the stent procedure is eliminated. Afterwards the balloon is deflated and the guide is removed. The advantages of distal occlusive balloons are the small diameter (2.2 French) and the good manoeuvrability and flexibility of the system. Possible disadvantages are that the occlusion is not tolerated by 6-10% of patients8 and it is not possible to image the vessel with contrast medium during the inflation.

Distal filter system
The protection filters consist of a metallic structure (or skeleton) coated by a membrane of polyethylene or a net of Nitinol™ wires that contain holes 80-200 µm in diameter [12]. The filters are usually positioned at the distal portion of a 0.014 inch guide. During the procedure, the filters are folded into a delivery catheter with which they are advanced distally to the stenosis. After the lesion is crossed, the filter is opened by removing the delivery sheath. At the end of the stenting procedure the filter is closed with a retrieval catheter and is removed from the carotid artery.

Systems of proximal protection
The distal protection devices - occlusive balloons or filters - have the disadvantage that they must cross the lesion before they are inflated or opened [13]. This passage (or crossing) carries the risk of embolisation during this 'unprotected' step of the procedure. The proximal protection systems, in contrast, provide cerebral protection before the passage of any type of device through the stenoses.

These systems consist of a long introducer sheath with a balloon that is inflated in the common carotid artery. A second balloon, inflated in the external carotid artery, assures the total blockade of the antegrade blood flow in the internal carotid artery. The proximal protection systems use the cerebral vascular connections of the Willis circuit. After the occlusion of the common and external carotid artery, the collateral flow through the Willis circuit will create so-called 'back-pressure', which will prevent antegrade flow in the internal carotid artery. After stent positioning, and before the deflation of the balloons in the common and external carotid artery, the blood present in the internal carotid artery - possibly containing dislodged debris - is aspirated and removed.

The advantage of the proximal protection system is the fact that the entire procedure is carried out under protection and, if it is correctly applied, it should completely avoid any type of embolisation. The disadvantages of the proximal protection system are that it is not tolerated by all patients and that the two systems actually available (Parodi™, Mo.Ma™) require 10 French introducer sheaths.

Clinical results
In the recent Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy trial (SAPPHIRE), 156 patients were randomised to carotid stenting with cerebral protection and 151 patients to endarterectomy [14]. The 30-day incidence of stroke/death in the group of patients treated by CAS was 4.5% and in the group treated by CEA was 6.6% (p=not significant). The SAPPHIRE study clearly shows that both procedures are at least equivalent in high-risk patients. If CAS performs at least as well as CEA in difficult patients, why should it work less well in patients at 'normal' risk? Kastrup et al. reviewed data from published single-centre reports of 2537 unprotected and 896 protected CAS procedures [9]. The 30-day death/stroke rate was 1.8% for patients treated with protection compared with 5.5% in patients treated without protection. However, no randomised trials are available to show the superiority of protected over unprotected CAS and it is difficult to imagine that such a randomised controlled study of protected versus unprotected CAS will ever be carried out. Primarily, such a study would require too many patients to show a difference between groups, considering the low reported complication rates of the procedure. However, the use of these protection devices has some advantages: firstly, a demonstrated capacity to capture debris which otherwise would have embolised; secondly, the reduction of emboli as shown by transcranial Doppler studies; [8] thirdly, an increase in experience using these devices with a low incidence of device-related complications [3]; and finally, the availability of second-generation devices featuring much higher flexibility, lower crossing profile, and easier handling.

Conclusions
Carotid artery stenting is emerging as an alternative, less invasive therapy for the treatment of carotid stenoses. Cerebral protection devices have been used successfully in large series of CAS and low periprocedural complication rates have been obtained. Based on the documented feasibility and safety of protection-device handling [3] and the previously shown capacity of protection devices to reduce embolisation of debris into the cerebral circulation [6], it appears prudent to consider cerebral protection mandatory for any carotid artery stent procedure.

With respect to the controversy surrounding endovascular versus surgical therapy, the results of the first randomised studies and data from the registers of CAS with cerebral protection indicate outcomes similar to those obtained from the best surveys of surgical endarterectomy.

Key Learning
  • Embolic neurological events occur invariably during carotid artery stenting (CAS) despite advances in technique, technology and anti-thrombotic regimens
  • The risk of embolic neurological events can be minimised using cerebral protection devices:
    • distal occlusive balloons
    • distal filter systems
    • proximal protection systems (occlusion of the common and external carotid arteries)
  • Distal devices have to cross atheromatous plaque before deployment, increasing the risk of embolisation without cerebral protection in place
  • A proximal protection system can provide cerebral protection from any type of embolisation throughout the procedure
  • Available data support the use of cerebral protection devices during CAS

References
  1. Roubin SG, New G, Iyer SS, et al. Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis. A 5-year prospective analysis. Circulation 2001;103:532-7.
  2. Endovascular versus surgical treatment in patients with carotid stenosis in the carotid and vertebral artery transluminal angioplasty study (CAVATAS): a randomised trial. Lancet 2001;357:1729-37.
  3. Reimers B, Schlüter M, Castriota F, et al. Routine use of cerebral protection during carotid artery stenting: results of a multicenter registry of 753 patients. Am J Med 2004;116:217-22.
  4. Imparato AM, Riles TS, Gorstein F. The carotid bifurcation plaque: pathologic findings associated with cerebral ischemia. Stroke 1979;10:238-45.
  5. Ohki T, Roubin GS,Veith FJ, et al. Efficacy of a filter device in the prevention of embolic events during carotid angioplasty and stenting: an ex vivo analysis. J Vasc Surg 1999;30:1034-44.
  6. Angelini A, Reimers B, Dalla Barbera M, et al. Cerebral protection during carotid artery stenting: collection and histopathologic analysis of embolized debris. Stroke 2002;33:456-61.
  7. Crawley F, Clifton A, Buckenham T, et al. Comparison of hemodynamic cerebral ischemia and microembolic signals detected during carotid endarterectomy and carotid angioplasty. Stroke 1997;28:2460-4.
  8. Al-Mubarak N, Roubin GS,Vitek JJ, et al. Effect of the distal-balloon protection system on microembolization during carotid stenting. Circulation 2001;104:1999-2002.
  9. Kastrup A, Groschel K, Krapf H, et al. Early outcome of carotid angioplasty and stenting with and without cerebral protection devices: a systematic review of the literature. Stroke 2003;34:1936-41.
  10. Brooks WH, McClure RR, Jones MR, et al. Carotid angioplasty and stenting versus carotid endarterectomy: randomized trial in a community hospital. J Am Coll Cardiol 2001;38:1589-95.
  11. Theron J, Courtheoux P, Alachkar F, et al. New triple coaxial catheter system for carotid angioplasty with cerebral protection. Am J Neuroradiol 1990;11:869-74.
  12. Reimers B, Corvaja N, Moshiri S, et al. Cerebral protection with filter devices during carotid artery stenting. Circulation 2001;104:12-5.
  13. Adami CA, Scuro A, Spinamano L, et al. Use of the Parodi anti-embolism system in carotid stenting: Italian trial results. J Endovasc Ther 2002;9:147-54.
  14. Yadav J. Oral presentation at the 75th Annual Scientific Sessions of the American Heart Association, Chicago, November 2002.



December 2004, 1098/OS