Limiting Complications During Carotid Artery Stenting in Complex Lesions

Login or register to view PDF.
Abstract

Stroke is the third leading cause of death and permanent disability in the US and Europe. During the last decade, carotid artery stenting (CAS) has gained a role as an alternative option to carotid endoarterectomy (CEA). Both patient selection and plaque morphology are crucial to reduce the risk of complications. Technical aspects such as the employment and selection of different types of cerebral protection devices, distal occlusion balloons, filters, proximal protection systems and stent selection will be widely discussed.

Disclosure
The authors have no conflicts of interest to declare.
Correspondence
Fabrizio Fanelli, Vascular and Interventional Radiology Unit, University of Rome 'La Sapienza', 324 Viale Regina Elena 00161, Rome, Italy. E: fabrizio.fanelli@uniroma1.it
Received date
09 July 2010
Accepted date
10 August 2010
DOI
http://dx.doi.org/10.15420/icr.2010.5.1.66

Stroke is the third leading cause of death and permanent disability in the US and Europe. It is estimated that there are over 700,000 new cases of stroke each year in the US, of which 20–30% are thought to be secondary to carotid thromboembolic disease.1 In the last few years, carotid artery stenting (CAS) has significantly expanded as an alternative treatment to the conventional surgical carotid endarterctomy (CEA). Several trials have been performed comparing carotid endoarterectomy CEA versus CAS. Not only interventional radiologists but also vascular surgeons, cardiologists and neuroradiologists are nowadays involved in this highly specialised procedure owing to the numerous advantages of the technique. However, CAS is associated with an incidence of neurological complications ranging from 3.2 to 10.9% owing to distal embolisation.2 In order to reduce the risk of peri- and post-procedural complications, it is mandatory to perform:
• accurate patient selection; • complete pre-procedural evaluation of the vessel anatomy and plaque characteristics; and • valid medical therapy.
Moreover, operator experience is a key factor in the evaluation of the results.

Patient Selection

Indications for CAS are continuously evolving. Following the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, indications for CAS are:3
• symptomatic patients with stenosis >50%; • asymptomatic patients with stenosis >80%; and • asymptomatic patients with stenosis >50% in the presence of a complex plaque morphology.

Moreover, carotid stenting is also indicated in patients with high-risk factors for surgery:4
• age >80 years; • restenosis after surgical endoarterectomy; • stenosis with occlusion of contralateral internal carotid artery; • tandem lesions; • carotid dissection; • pseudoaneurysms; • stenosis in patients with ‘hostile neck’; • surgically inaccessible lesions; • poor cardiac ejection fraction (<30%); • uncontrolled arrhythmias, unstable angina, heart failure (New York Heart Association [NYHA] classification class IV); and • bleeding disorders.

Plaque Morphology Assessment

A pre-treatment imaging evaluation is mandatory to obtain all of the information about the degree of stenosis, the plaque morphology and the anatomical characteristics to allow better stent and cerebral protection device (CPD) selection.
An atherosclerotic plaque is a focal lesion of the intimal layer consisting of a lipidic core encased in a fibrous cap and covered by the endothelium.
According to their morphology, atherosclerotic lesions can be classified as ‘stable’ or ‘vulnerable’. Stable plaques consist of a great amount of smooth-muscle cells and collagens with a small lipidic pool; this homogeneous fibrous structure protects the plaque surface from disruption, reducing the risk of thrombosis. Vulnerable plaque presents a thin fibrous cap while the core is composed of extracellular lipidis and a few smooth-muscle cells.

The considerable number of inflammatory cells (macrophages, T lymphocytes, dendritic cells and mast cells) stimulate and regulate the inflammatory response inside the plaque, leading to the production of pro-inflammatory cytokines and protease responsible for the degradation of the fibrous cap. Vulnerable plaques are also characterised by new vessel formation, predisposing to intra-plaque haemorrhage that may lead to rapid plaque expansion and acute disruption. These micro-vessels also express a high concentration of adhesion molecules associated with inflammatory cell recruitment, suggesting that they play an active role in the formation of leukocyte infiltrates inside the plaque. A defect of the fibrous cap causes exposure of the lipidic core to blood cells, with the subsequent activation of the clotting system leading to thrombotic complications such as embolism or complete thrombotic occlusion of the vessel.
Plaque morphology can be studied in vivo using several approaches, such as B-mode ultrasound (US), computed tomography (CT) and magnetic resonance angiography (MRA).

Ultrasound

Thanks to its ability to evaluate the morphological characteristics of the plaque and the haemodynamic abnormalities related to stenosis grade, and its cost-effectiveness, colour Doppler US (USCD) is considered to be the gold standard for the initial assessment of carotid disease. B-mode greyscale US depicts atherosclerotic plaques and the intima-media thickness (IMT), while USCD evaluation allows simultaneous analysis of the vascular lesion and haemodynamics; furthermore, it assists in the evaluation of the spectral analysis at the level of the stenosis and helps distinguish between critical stenosis and occlusion. Several studies have shown a correlation between plaque echogenicity and histopathological characteristics: hypoechoic and heterogeneous plaque indicates both intra-plaque haemorrhages and the presence of a large lipidic pool, whereas a fibrous plaque appears hyperechoic and homogeneous.
Computer-assisted plaque characterisation using standardised B-mode US imaging and digital post-processing allow a quantitative evaluation of the echodensity using the greyscale median (GSM). A GSM value <25 indicates low echogenicity (echolucency), which is associated with complex plaque composition and a higher risk of developing neurological events, while a GSM >25 characterises stable fibrous plaque.5

USCD can be considered the method of choice in the screening phase as it provides initial information about the carotid anatomy, plaque morphology and haemodynamic parameters; however, despite the progress in technical equipment there is still a lack of uniformity in practice and interpretation between operators, so standardised protocols are desirable to increase the reproducibility and reliability of the information provided by carotid ulrasound.

Computed Tomography Angiography

The recent introduction of multidetector-row spiral CT has substantially improved the image quality and diagnostic performance of CT angiography (CTA) by allowing high spatial and temporal resolution. Many authors have reported the high sensitivity, specificity and accuracy of CTA in the evaluation of carotid artery disease; in addition, this technique allows anatomical visualisation of the aortic arch and supra-aortic vessels, giving important information to the operator about the best catheterisation technique to use in each patient.6

Magnetic Resonance Angiography

With an adequate acquisition protocol, MRA allows good visualisation of the common carotid artery origin, the innominate trunk, carotid bifurcation, the extra- and intra-cranial internal carotid artery and the circle of Willis. Various MRA techniques have been proposed, such as 2D or 3D time-of-flight (TOF) and phase-contrast (PC) MRA. Despite providing good vessel depiction, some disadvantages have been reported, such as overestimation of the degree of stenosis when high-grade vessel narrowings or slow flows are present. Contrast-enhaced 3D MRA is currently considered to be the method of choice for imaging the head and neck vasculature. The acquisition protocol includes a T1- weighted coronal plane sequence during the first pass of paramagnetic gadolinium-based contrast medium. Moreover, plaque composition can also be assessed using high-resolution magnetic resonance imaging (MRI), which provides more detailed images of the plaque. The plaque components, such as the necrotic core and the fibrous cap, present a characteristic appearance and can be qualitatively determined.

Role of Cerebral Protection Devices

As reported by various authors,7,8 intracranial distal embolisation from plaque debris mobilisation is the most frequent and severe complication of this technique. The initial results of this procedure have shown an incidence of neurological complications ranging from 3.2 to 10.9% owing to distal embolisation.2 To overcome this great difficulty, several cerebral protection devices (CPDs) have been developed in recent years in order to reduce the complication rate by preventing distal embolisation, especially in those patients with unstable and complex plaque morphology.9 However, the role of CPDs is still under clinical investigation, and it also remains unclear whether the reduction of neurological complications is owing to the use of CPD or to the improvement of the devices.
Large series of patients have been reported by several authors with a significant reduction of major neurological events associated with the use of CPD: Kastrup et al. (from 5.5 to 1.8%)10 and Bolthuc et al. (from 3.8 to 1.2%).11 Moreover, Kastrup et al.12 performed a cumulative review of the most relevant publications between 1990 and 2002, comparing 2,537 unprotected CAS with 896 CAS performed using CPDs. The combined stroke and death rate within 30 days in both symptomatic and asymptomatic patients was higher in the group of patients treated without a CPD: 5.5% compared with 1.8% of the protected group (p<0.001%). These results have confirmed the idea that CPDs should be routinely used during CAS to prevent embolic events. Some complications can also occur with the use of CPDs, correlated with failure to capture the emboli, vasospasm and vessel wall injury and during the retrieval phase of the filters.13,14
CPDs can be divided into three different types according to technical aspects: distal occlusion balloons, filters and proximal protection systems. Using filter systems, blood flow is maintained through the internal carotid artery (ICA) and emboli are captured and removed together with the device. Balloon occlusion devices and proximal protection systems completely occlude the flow into the ICA and emboli must be aspirated before balloon deflation or catheter removal.

Distal Occlusion Balloons

Distal occlusion balloons represent the first CPD routinely used in clinical practice. They consist of a 0.014-inch guidewire equipped with a distal balloon inflated through a small channel present within the wire. Once the lesion is crossed with the guidewire, the balloon is positioned above the lesion and inflated to completely occlude the ICA, thus avoiding the passage of micro-emboli into the intracranial circulation.

After treatment of the lesion with angioplasty and stenting, a guiding catheter is advanced up to the balloon to aspirate the blood, possibly containing the debris dislodged from the atheroma. After complete aspiration of the blood present in the ICA, the balloon is deflated and the guidewire removed. The advantages of this system are represented by the very low profile of the balloon-wire crossing the lesion (≤2.2Fr) associated with the very high flexibility and torque of the system.15 On the other hand, the system produces complete occlusion of the ICA and this haemodynamic condition cannot be well tolerated by 6–10% of patients.16 Moreover, it is not possible to obtain continuous visualisation of the lesion during the procedure as the blood flow is completely blocked and contrast media injection is not possible.

Filters

Filters consist of a metallic structure coated with a membrane made of polyethylene. The membrane of the filters may have different shapes and presents several pores with a diameter ranging from 80 to 220μm. Filters are mounted on a 0.014-inch guidewire, are generally 30mm proximal to a flexible tip and are delivered through a very-small-profile catheter (≤3Fr). Once the lesion is crossed, the filter should be opened in a straight portion of the ICA at least 2cm above the lesion. At the end of the stenting procedure, a retrieval catheter is inserted to re-capture the filter and remove it. In cases of very tight stenosis or very tortuous anatomy, the passage of the delivery catheter through the lesion may be difficult or impossible. In such cases, pre-dilation of the stenosis must be performed using a very small (2–3mm) balloon to avoid fracturing the plaque or stimulating the vagal sinux reflex. The diameter of the filter must be selected according to the calibre of the ICA segment where the filter will be placed. Generally, a filter diameter 1mm larger than the size of the artery is required to obtain correct wall apposition of the filter, reducing the possibility of failure to capture the emboli. As filters produce a marked reduction of the blood flow within the ICA, they should not be left in place for more than 15 minutes. Different types of distal filter are available on the market and others will appear in the future. Filters differ in terms of the rigidity of the metallic structure, the diameter of the pores and wire stiffness. A detailed knowledge of the technical characteristics of the various filters is essential for selecting the correct device on the basis of patient characteristics and avoiding any complications (see Figures 1–5).

Proximal Protection Systems

Distal occlusion balloons and filters have the disadvantage that the stenotic lesion must be crossed in order to place the device. This manoeuvre carries the risk of complete lumen occlusion and distal embolisation, especially in cases of unstable and complex plaques (ulcer, fresh thrombus). By contrast, proximal protection systems provide cerebral protection without the need to advance any type of device through the stenosis, reducing the risk of distal embolisation. These devices are based on the inflation of an occlusion balloon at the level of the common carotid artery (CCA) and at the origin of the external carotid artery (ECA), causing inversion of flow (Parodi system) or complete cessation of flow (Mo.Ma® device) within the ICA. These systems take advantage of the vascular anastomoses of the circle of Willis: after occlusion of the common and external carotid arteries, the collateral flow through the circle of Willis creates a ‘back pressure’ that will prevent antegrade flow into the ICA. After stenting of the lesion, the stagnant blood present within the ICA, possibly containing embolic material, is aspirated and filtered or removed.
The advantages of these systems are that the entire procedure can be performed under protection, reducing the risk of distal embolisation. On the other hand, we have to consider a more complex procedure using a large device. However, proximal protection systems cannot be used in all cases because complete flow occlusion is not tolerated by 6–10% of patients.17

Stent Selection

After early experiences with the use of balloon-expandable stents, nowadays the wide variety of self-expandable stents allows the choice of different stents on the basis of plaque characteristics and anatomical findings, so knowledge of the structural characteristics of the different stents is mandatory to improve CAS outcome. Two of the main properties that influence the choice of stent are flexibility and scaffolding. In cases of tortuous anatomy, the use of a flexible stent prevents vessel kinking. Closed-cell stents are the most rigid and tend to stretch the treated area. In cases of complex plaque morphology, a low scaffolding may cause distal embolisation and stroke owing to squeezing plaque material through the cells. In this case a closed-cell design offers the maximal scaffolding to the vessel wall. A joint-geometry stent is available on the market that combines both characteristics, with an open-cell design at the proximal and distal portion (to improve stent flexibility) and a closed-cell design in the middle portion to provide better scaffolding, reducing the risk of plaque prolapse.

Medication

All patients undergoing a CAS procedure should recive antiplatelet therapy to reduce the risk of myocardial infarction, stroke or vascular death. According to recent protocols, before CAS all patients should be pre-medicated with aspirin 325mg/day starting 72 hours before the procedure and with clopidogrel 75mg/day at least 24 hours before. During the procedure and immediately after arterial access, 5,000IU of heparin is administered to allow an activated clotting time (ACT) of 275–300 seconds. Atropine 1mg is administered only immediately before post-stent balloon angioplasty. Post-procedure medical protocol is based on low-molecular-weight heparin 0.8ml/day associated with clopidogrel 75mg/day for four weeks. Afterwards, aspirin 325mg/day or clopidogrel 75mg/day is administered indefinitely. Moreover, recent studies have shown a role of statins in the stabilisation of plaque, reducing the risk of myocardial infarction and stroke.18 Ôûá

References
  1. American Heart Assocation, 1999 Heart and Stroke Statistics Update, Dallas: American Heart Association, 1998:13–15.
  2. Zahn R, et al., Z Kardiol, 2005;94(3):163–72.
    Crossref | PubMed
  3. Narins CR, Illig KA, J Vasc Surg, 2006;44:661–72.
    Crossref | PubMed
  4. Nguyen LL, et al., Semin Vasc Surg, 2004;17:219–23.
    PubMed
  5. Biasi GM, et al., Circulation, 2004;110:756–62.
    Crossref | PubMed
  6. Marcus CD, et al., Radiology, 1999;211:775–80.
    Crossref | PubMed
  7. Coggia M, et al., J Vasc Surg, 2000;31:550–57.
    Crossref | PubMed
  8. Moody DM, et al., Ann Thorac Surg, 1995;59:1304–7.
    Crossref | PubMed
  9. Theron J, et al., Am J Neuroradiol, 1990;11:869–77.
    PubMed
  10. Kastrup A, et al., Stroke, 2003;34:813–19.
    Crossref | PubMed
  11. Boltuch J, et al., J Endovasc Ther, 2005;12:538–47.
    Crossref | PubMed
  12. Kastrup A, et al., Stroke, 2003;34:813–19.
    Crossref | PubMed
  13. Ohki T, et al., Endovascular Today, 2003;9:37–9.
  14. Shaw JA, et al., Catheter Cardiovasc Interv, 2005;64: 18–22.
    Crossref | PubMed
  15. Henry M, et al., J Endovasc Surg, 1999;6:321–31.
    PubMed
  16. Al-Mubarak N, et al., Circulation, 2001;104:1999–2002.
    Crossref | PubMed
  17. Boltuch J, et al., J Endovasc Ther, 2005;12:538–47.
    Crossref | PubMed
  18. Amarenco P, et al., Lancet Neurol, 2004;3:27–8.