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Stent supported Carotid Artery
Angioplasty as Prevention of Stroke

Jiri Vitek*

Sriram Iyer, Gary Roubin
Lenox Hill Heart and Vascular Institute of New York,
New York, NY, USA

 

Carotid artery stenting (CAS) is being investigated as an endovascular alternative to carotid endarterectomy (CEA) for the treatment of obstructive carotid stenoses. The goal of both procedures is to prevent stroke caused by extracranial carotid disease. CAS offers patients a less invasive and less traumatic means of achieving this goal. The efficacy of CAS in preventing stroke depends on the ability of the operator to achieve complication-free results by careful consideration of the patients selected and meticulous performance of the intervention. The recent application of embolic protection devices, designed to capture embolic matter released during the stenting procedure before it reaches the brain, has added an important dimension to the performance of safe carotid stenting. This report provides a step-by-step approach to the clinical and technical aspects of the carotid stenting procedure in an effort to ensure safer outcomes.

Carotid angioplasty and stenting (CAS) has evolved rapidly over the last decade. Since Dotter, Judkins [1,2], and Grüntzig’s [3] pioneering work, few procedures have met with such vigorous scrutiny and criticism as carotid stenting. Given the potential for procedural neurological complications and the existence of a well-validated surgical approach, caution has always been warranted. In the case of carotid stenting, opposition in the U.S. surgical community [4] has delayed the approval of advanced devices and techniques, slowed progress in clinical trials, and has created limited access for patients who might benefit from the procedure. However, despite resistance, carotid stenting has become widely accepted as a viable alternative to carotid endarterectomy (CEA).

 

Historical Perspective
CEA was introduced in the early 1950s for the prevention of embologenic etiology of stroke from atherosclerotically narrowed carotid bifurcation and internal carotid artery (ICA). By the early 1990s, at least three prospective randomized trials had demonstrated that CEA indeed reduced the risk of stroke in patients with carotid stenoses [5–7]. The results of these trials confirmed a large body of prospective observational data that suggested a benefit of surgery over medical therapy, depending on symptom status and the severity of stenosis. Furthermore, the data confirmed the view that if the periprocedural stroke and mortality risks of CEA were low, patients benefited. However, prospective trials documented a significant perioperative risk that had not been highlighted by the surgeons. In NASCET (North American Symptomatic Endarterectomy Trial), in addition to a 5.8% rate of neurological complications, the 30-day adverse events that were associated with the open surgical procedure were:

• Perioperative cranial nerve damage (5.6%).
• Medical complications (8.1%).
• Myocardial infarction (MI, 1.2%).
• Congestive heart failure (CHF, 1.2%).
 (Additionally all patients required general anesthesia.)

In the 1980s, interventional radiologists started to cautiously approach stenotic afflictions in the carotid arteries. In 1977 and 1980, Mathias et al. reported successful results with the use of percutaneous angioplasty for carotid stenosis [8, 9]. In the early 1980s, Hasso et al. and Belan et al. reported successful ICA angioplasty in fibromuscular dysplasia [10,11], and 1983 saw Bockenheimer et al., Wiggli and Gratzl, Tsai et al., and Theron et al. publish their results on carotid angioplasty in atherosclerotic disease [12–15]. In 1984, Rabkin et al. reported on the experimental use of intravascular Nitinol stents [16], and Theron et al. [17] began their pivotal work with distal balloon protection during carotid bifurcation angioplasty, later supplemented by stents. From a historical perspective, the first insertion of a (glass) tubular structure into the blood vessel of an animal was reported by Carrel in 1912 [18]. Use of silastic tubes was attempted by Dotter in 1969, but these were shown to thrombose and migrate [19]. In 1983, Dotter et al. reported the use of uncoated stainless steel or nickel titanium alloy wire coils with more success [20]. In the same year, Cragg et al. [21], and 1 year later, Maass et al. [22], reported on using nitinol spiral endoprostheses in animal experiments. Less known is the fact that, in 1973, Kononov [23] implanted a balloon expandable stent graft into a dog’s aorta. After multiple successful experiments, on May 5th, 1979, he obtained a patent on a “device for implanting a prosthesis in a tubular organ”. In 1990, Rabkin et al. [24] reported that they had been successfully implanting Nitinol self-expandable stents inhuman iliac arteries since 1984. The successful placement of an endovascular graft transluminally to treat a patient with iliac artery occlusive disease was achieved by Volodos et al. in 1985 [25].

As was the case in other arterial sites, the evolution and availability of arterial stents transformed the less predictable carotid balloon angioplasty, and by the early 1990s prospective observational studies of carotid stenting had been initiated [26–29]. From the outset, carotid stenting performed by experienced operators produced acceptable outcomes, with a 1% rate of major complications. Non – disabling neurological events (approximately 6%) were found in

patients with advanced age and more complex, severe stenoses [30]. Given the nature of the carotid lesion, the incidence of embolic neurological events was not entirely unexpected, and led to the development of embolic protection techniques and devices. In 1983, Vitek et al. reported angioplasty of the innominate artery with distal occlusion balloon protection of the common carotid artery (CCA) [31]. Henry et al. [32] perfected Theron’s technique [17] with a low profile occlusion balloon system for embolic protection. Parodi et al. [33] focused on proximal occlusion devices that facilitated embolic protection by temporarily reversing flow in the ICA. Recently, several distal embolic filter devices have been developed. As different embolic protection systems became available, a number of single-center studies and multicenter registries confirmed the ability of experienced operators to achieve excellent results with CAS, with a remarkably low risk of embolic complications [34–37]. Consequently, the simplicity of this less invasive approach together with its low morbidity rate has accelerated the acceptance of CAS in medical community.

 

Indications
In general, the indications for CAS are similar to those for carotid surgery with respect to symptomatic status and severity of carotid stenosis. There are notable exceptions to this therapeutic principle. Subsets of patients are emerging as better candidates for CAS, while others appear to be better candidates for CEA. Patients who have co-morbid medical conditions that would increase the risk of an open surgical procedure or the use of general anesthesia are primary candidates for stenting. Based on results from the recent SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial [38], these conditions include:

 • Age >80 years.
 • CHF and/or severe left ventricular dysfunction.
 • Opened heart surgery needed within 6 weeks.
 • Recent MI.
 • Unstable angina.
 • Severe pulmonary disease.

In addition, any condition that would increase the risk of surgery represents a probable indication for CAS, including:

 • Isolated brain hemisphere by arterial supply.
 • Contralateral occlusion of the ICA.
 • Prior ipsilateral endarterectomy.
 • Prior neck dissection or radiation.
 • High lesions behind the mandible.
 • Low lesions that require thoracic exposure.

The advantage of an endovascular approach is that the angiographic status (anatomy, collaterals, status of circle of Willis, intracranial lesions, and flow characteristics) is usually well defined prior to the stenting procedure. Although not emphasized in the carotid surgery trials, the incidence of cranial nerve damage, wound hematoma, and infection are also significant and must be considered before referring the patient for neck surgery.

 

Contraindications
There is a number of notable relative contraindications to carotid stenting. Patients who are intolerant to a combination of antiplatelet agents are more safely managed with CEA. Similarly, CEA may be a better option if the patient has a compelling reason to undergo a major surgical procedure within 3–4 weeks that will require the cessation of antiplatelet therapy. Another relative contraindication to CAS is the presence of chronic renal failure, although experienced operators can complete the procedure using 50–75 cc of contrast or use Gadolinium contrast. The important relative anatomical contraindications that increase the risk of performing CAS are:

• Severe diffuse atherosclerotic disease, calcifications, elongation, and tortuosity of the brachiocephalic vessels and aortic arch, which make access to the carotid bifurcation difficult, riskier, and occasionally impossible (Figure 1A and 1B).
• Severe tortuosity in the region of the carotid bifurcation (Figure 1C).
• Severe calcification completely surrounding the stenotic segment (Figure 1D).

 

Figure 1: Lesions unsuitable for CAS.
a. Diffuse atherosclerotic disease in the common carotid artery (CCA).
b. Anatomically unsuitable approach due to the tortuosity of the CCA.
c. Severe tortuosity of the internal carotid artery (ICA) preventing safe placement of the protection device and stent.
d. Heavy circumferential, concentric calcifications and distal tortuosity.

Placement of embolic protection systems, guide wires, and stents is much more complicated in such anatomical conditions, and the degree of tortuosity can be substantially increased after placement of a carotid access sheath (Figure 2). In addition, the presence of a mobile thrombus should be ruled out before CAS.

 

Figure 2: Kink created (arrow) in the distal segment of the ICA by placement
of the sheath in the CCA (bifurcation displaced cephalad).

The conditions that are not define as a contraindications for CAS include intracranial stable aneurysms, AVMs, and fistulas. Critical control of hypertension and modulation of anticoagulation is mandatory in these conditions.

 

Management of the Procedure
The carotid stenting protocol in the Lenox Hill Heart and Vascular Institute (LHHVI, New York, NY, USA) has been described in detail previously [39]. In the pre-procedural management of patients, adequate dual antiplatelet therapy is vital. On the day of the procedure, oral antihypertensive therapy is withheld and the patient must be well hydrated. Mild sedation may be offered to anxious patients prior to the procedure but for the vast majority gentle reassurance combined with local anesthesia is all that is necessary. This approach also facilitates continuous, accurate pre-, intra-, and post-procedural neurological monitoring. Intra-procedural monitoring can be accomplished by engaging in verbal contact with the patient and by having them squeeze a toy placed in the contralateral hand after every step of the intervention. Pulse oximetry, intra-arterial pressure and heart rate monitoring, and careful control of hemodynamics are essential elements of the procedure. Atropine (0.6–1 mg) should be administered after placement of the sheath in the CCA to suppress the baro-receptors. If the blood pressure remains elevated after the stenosis has been relieved, it should be rapidly lowered using intravenous nitroglycerine, nitroprusside, or another appropriate rapidly acting agent. When an occlusion balloon embolic protection system is used, the blood pressure should be lowered before the protection balloon is deflated. Occasionally, substantial hypotension is noted after post-dilation of the stent, particularly in elderly patients. However, the hypotension is invariably benign and does not require aggressive treatment. Patients who have separate critical disease in the intracranial, extracranial, or coronary vessels should be treated with intravenous phenylephrine, aggressive hydration, and, occasionally, dopamine infusions. Anticoagulation during stenting is critical, but only modest anticoagulation levels (activated clotting time [ACT] 200–250 s) are necessary and should be monitored during the intervention. Depending on body weight, either heparin (4000 IU) or bivalirudin is used. Glycoprotein IIb/IIIa receptor antagonists are not used in our center.

The current CAS technique requires the use of 6-F femoral access sheaths; femoral closure devices are used frequently before the patient leaves the interventional suite. Accordingly, patients can sit up and begin to ambulate almost immediately. This allows full neurological assessment, and the subsequent natural release of catecholamine counteracts much of the bradycardia and hypotension associated with stent placement. Intensive post-procedural care is unnecessary. Instead, patients should be managed in a monitored bed with nursing staff who are familiar with post-CAS patient care. If the sheath is not removed in the interventional suite with femoral closure systems, it should be removed as soon as possible by experienced personnel once the ACT has fallen to <150 s. These patients do not require prolonged heparinization and, if the access site is stable, they do not require bed rest, sedation, or narcotics, all of which exacerbate hypotension and mitigate against rapid ambulation. All patients with hypotension should be well hydrated, have routine hematocrit checks, and undergo groin examination. It is important that other important causes of hypotension, such as retroperitoneal bleeding, are not overlooked. Patients who have an uncomplicated procedure and percutaneous femoral closure device can be discharged on the same day.

Patients are discharged on a combination of clopidogrel (75 mg) and aspirin (325 mg) for 1 month, after which aspirin is continued indefinitely. The exception to this regimen are patients treated for post-CEA or post-radiation stenosis in whom the Plavix/aspirin treatment is extended for approximately 1 year. Baseline ultrasound duplex studies within 1 month serve as a reference for future follow-up evaluations in these patients. Frequently, despite good angiographic results, blood velocities within the stent become elevated. However, the evidence to date suggests that this finding is not predictive of excessive progression of neointimal proliferation or restenosis [40]. Magnetic resonance angiography is not used for follow-up purposes due to signal dropout associated with the metallic stent. Computerized tomographic angiography, however, has shown some promise and may prove to be the follow-up modality of choice. Significant angiographic restenosis >80% is an uncommon finding. Cases of restenosis are seen more commonly in patients with stenosis associated with radiation-induced injury and in those treated for post- CEA restenosis. Restenosis occurring after stent placement can be managed by repeat balloon dilation and, occasionally, by additional stenting.

 

Stenting Technique
The stenting technique has been covered in detail previously (Figure 3 - 5) [39]. Transcranial Doppler studies have shown the importance of performing the intervention with minimum manipulation of the lesion. If significant difficulties are encountered during sheath placement or passing the guide wire or embolic protection device, the decision to proceed must be reassessed. Few embolic particles are generated during careful sheath placement or crossing the lesion with an embolic protection system; a modest number of particles is released with pre-dilation, followed by stent deployment; and the largest number of particles is released during post-dilation of thestent.

 

Figure 3A: a. Collapsed ICA with 98% ostial stenosis. (Recanalized occlusion?)
b. Pre-predilatation with 2 x 40 mm balloon over 0.014” Choice PT.
            c. Guard wire occusion balloon advanced into the ICA and deployed.

 

Figure 3B: a. Pre-dilatation with 4 x 30 balloon.
b. Stent post-dilatation with 5x20 balloon.
c.Status post. CAS.

 

Figure 4 A: Placement of the (embolic protection device) filter
with the help of the “buddy wire”.
a. Symptomatic stenosis with angulation in the left ICA.
b. Stiffness of the Accunet filter prevents advancement.
c. 0.014” Stabilizer Plus advanced into the ICA.

 

Figure 4 B: a. Accunet filter advanced into the ICA.
b. Accunet filter opened. Stabilizer Plus removed.
c. Status post CAS.

 

Figure 5: Placement of the (protection device) occlusion balloon with the help
of the “buddy catheter”.
- 90 degree take-off of the left ICA with 80% angulated stenosis.
- “Buddy wire” (125 cm JR4 catheter) placed in the ostium of the ICA through the 6F sheath. Guard wire with occlusion balloon advanced through the JR4 catheter into the ICA.
- Guard wire balloon inflated.
- Status post CAS.

 

These observations support the view that if an embolic protection system cannot be passed through the lesion in a safe expeditious manner before pre-dilation, it can be deployed after mini 2-mm balloon pre-dilation (Figure 3) or just before stent post-dilation, which is less efficacious, but still useful.

If available, flow reversal embolic protection systems can be used (Figure 6) in patients who have an intact Circle of Willis and thus a good collateral supply in addition to suitable iliac and proximal carotid anatomy to facilitate placement of this higher profile device.

 

Figure 6: Arteria embolic protection system.
   a. 85% stenosis in proximal ICA.
 b. Stent post-dilatation with embolic protection system in place.
Occlusion of the CCA (large arrow). Occlusion of the ECA (small arrow).
c. Status post. CAS.

 

Transcranial Doppler studies also demonstrated the importance of minimum manipulation of the lesion with balloon dilation and stent placement. Pre-dilation of the lesion with a low-profile 4x40 mm length balloon reduces movement of the balloon during inflation. A single brief inflation is all that is required. Pre-dilation reduces the risk of embolization when advancing the higher profile stent delivery systems across the lesion. The stent should be deployed in one movement and be of sufficient length to cover the lesion from normal distal vessel to the CCA. There is no disadvantage in covering the external carotid artery (ECA) origin or leaving excess stent in the common carotid. Post-dilation should be done with a single well-positioned inflation with a conservatively sized, low-profile balloon ([5 or 5.5 mm] 20 mm). A second inflation in the same position has the effect of “shearing off” large amounts of plaque through the stent struts. Embolic protection systems are effective in abolishing, or markedly reducing, the volume of particles reaching the brain, but all of the devices can be overwhelmed by suboptimal techniques that release a large volume of debris.
CAS begins with varying degrees of diagnostic carotid angiography that should be tailored to the anatomical information gained from preceding noninvasive studies. It should be performed by experienced angiographers who are familiar with use of low profile, atraumatic, and safe neuroradiology diagnostic catheters and guide wires. In the LHHVI, we use double-curved 5-F catheters (Figure 7) and 0.038-inch angled-tip glide wires [39]. This system enables us (in 98.5% of patients) to selectively catheterize the CCA, ICA, and ECA, both subclavian arteries, and at least one vertebral artery [40]. The same catheterization technique is used for introducing a 6-F, 90-cm sheath into the CCA. The minimum information required for the procedure is the severity and anatomy of the bifurcation lesion to be treated, ipsilateral intracranial anatomy, and an assessment of disease and/or tortuosity involving the CCA. The latter is important for determining safe access with a guiding sheath. If occlusion-type embolic protection systems are to be used, an assessment of collateral supply from the contralateral vessel or posterior circulation is mandatory and complete cerebral angiography is recommended.

 

Figure 7: a. Shapes of available catheters for brachiocephalic angiography.
            b. Double-curved catheter used in the Lenox Hill heart and vascular Institute.

 

The stenting procedure itself has four components:

• The 6-F guiding sheath is placed into the distal CCA. Definitive angiograms reassess the lesion anatomy and enhanced tortuosity of the ICA, which is commonly
 encountered due to the cephalad displacement of the bifurcation by the sheath (Figure 2)
• The lesion is crossed with an embolic protection device that is deployed in a distal
 segment of the cervical ICA (Figure 3, 4, 5, 9).
• The lesion is pre-dilated with a single inflation, the stent is placed and post-dilated with a conservatively sized, low profile balloon (Figure 3Bb, 6b).
• The embolic protection system is removed and final extracranial and intracranial
 angiography is performed. Using contemporary, rapid exchange (monorail) filter,
 balloon, and stent systems, the entire process can take as little as 15–20 min.

Using contemporary, rapid exchange (monorail) filter, balloon, and stent systems, the entire process can take as little as 15–20 min.

 

Embolic Protection Systems
Embolic protection devices come in two forms (Figure 8). The first group has “umbrella”- or “windsock”-like micropore filters that are compressed in low profile sheaths and deployed distal to the lesion. Appropriate sizing and positioning of these devices provides good wall apposition and filtration efficiency. Numerous studies have documented the ability of these devices to capture plaque, thrombus, and cholesterol crystals that are ³100 mm in size [32–38]. After post-dilation of the stent, they are collapsed and removed from the patient. The advantage of the filters is that they provide continuous perfusion to the brain. The disadvantages include a higher profile than distal balloon occlusion systems, for some systems difficulty in tracking more angulated bifurcations and tortuous vessels, and issue of missing very small particles. Occasionally the “buddy wire” or the “buddy catheter” have to use to advance the embolic protection devices into the angulated or tortuous ICA. (Figure 4, 5)

 

Figure 8:  Embolic protection systems.

 

Balloon occlusion devices comprise the second group of embolic protection devices and are available in two systems. The most commonly used system is a low profile, soft latex balloon that occludes the distal ICA below the siphon (Figure 5, 9). Blood containing any debris is aspirated after the stent has been dilated, which, theoretically, removes all particles. The balloon is then deflated and removed. Compared with filters, this device is easier to track through tortuous vessels (Figure 9). The principle disadvantage of the device is that 5–10% of patients do not tolerate ICA occlusion [32]. In addition, particles can be diverted up the ECA and reach the cerebral tissue via ophthalmic or vertebral collaterals. Retinal infarction has also been noted in these patients. Rarely, significant dissection of the distal ICA occurs (Figure 10).

 

Figure 9: Distal balloon embolic protection system (Guard wire) in tortuous ICA.
a. 95% ICA stenosis. Distal ICA tortuosity.
b. Occlusion balloon in distal ICA (arrow). Post-dilatation of the stent.
c. Status post CAS.

 

Figure 10: Dissection of the ICA post. CAS with distal balloon occlusion.
a. 98% ICA stenosis.
b. Occlusion balloon in distal ICA (thick arrow).
c. Status post CAS. Dissection in the ICA (small arrows).
d. Stat. post stenting of the dissection.

 

An alternative proximal occlusion system utilizes a more complicated device that features a cuff balloon surrounding the guiding sheath, which occludes the distal CCA. A side port allows placement of a balloon that occludes the ECA; thus, the flow in the ICA is reversed as the blood is shunted back through the guiding sheath via a filter to the femoral vein (Figure 6 and 8). The theoretical advantage of this approach is the removal of all particles, even those that may be produced when crossing the lesion. Disadvantages include the large profile of the guiding catheter that necessitates a 10-11-F sheath in the femoral artery, and the somewhat more complicated set up procedure. Again, 5–10% of patients with “isolated hemispheres” do not have the physiology to promote reversal of flow and do not tolerate the absence of cerebral perfusion [32].

From a practical perspective, all of the devices described have been studied in well conducted prospective trials. When used by experienced operators in the correct anatomical situation, all of the embolic protection approaches have demonstrated excellent recovery of debris and excellent procedural outcomes.

 

The 3% Rule
As stated above, carotid artery revascularization can be justified in the asymptomatic patient only if the procedure can be accomplished with a complication rate >3% [6].With the widespread availability of CEA and carotid stenting, candidates for carotid revascularization have generally been selected for either procedure on the basis of the presumed surgical risk (the “conventional paradigm,” is presented (Figure 11). Low-risk surgical patients would usually be referred for CEA or be enrolled in a randomized clinical trial of surgery versus stenting. Patients considered at high risk for open surgery were often referred for carotid stenting, arbitrarily considered a low-risk intervention because little attention had been given to definition of the risks associated with the latter procedure. However, it is of crucial importance to recognize the risks of carotid stenting and to realize that in certain patients (easily identified by readily available clinical and angiographic features), particularly those with asymptomatic lesions, the risks of procedure-related major adverse events might exceed the long-term risk of ipsilateral stroke with medical therapy. We believe that for the full clinical potential of carotid stenting to be realized, a paradigm shift needs to be implemented in the process of procedural risk stratification and selection of patients for revascularization. This applies both to everyday clinical practice and to the design of randomized trials. Clinical decision making that incorporates these principles is depicted here. (Figure12). The category of “high risk” patients for CAS should be recognized.

 

Figure 11: Traditional, conventional paradigm for CAS.

 

Figure 12: New proposed paradigm for CAS.

 

Implementing the 3% Rule
In determining the risk of death or stroke associated with carotid stenting, it is of critical importance to recognize 4 factors that have been associated with increased procedural complications (Figure 13). The most important of these factors is advanced age. In the lead-in phase of the multicenter CREST trial, the risk of 30-day stroke or death among 749 patients was directly related to age (<60 years, 1.7%; 60 to 69 years, 1.3%; 70 to 79 years: 5.3%; and >80 years, 12.1%; P-0.006) [41]. Although the risk attributable to advanced age in this analysis appeared to be independent of other clinical (eg, gender or symptom status), angiographic (eg, lesion severity), or procedural (eg, use of distal protection devices) factors [41] it is likely that the increasing prevalence of the other factors listed (Figure 13) with advanced age accounts, at least in part, for this association. Decreased cerebral reserve is another important factor when one considers the risk of carotid stenting. Carotid revascularization (carotid stenting or CEA) is usually associated with some degree of cerebral embolization that is generally well tolerated in patients with good cerebral reserve; however, patients with prior strokes, lacunar infarcts, microangiopathy, or dementia of varying stages are much more likely to experience neurological deficits after carotid stenting. This risk is markedly amplified in the presence of an isolated hemisphere with lack of good collateral support. Although some lesion characteristics (eg, degree of stenosis and length) indicate potential technical difficulties, the 2 most important anatomic findings portending an increased procedural risk are vascular tortuosity and heavy concentric calcification (Figure 1c, d). Excessive tortuosity is defined as 2 bend points that exceed 90°, within 5 cm of the lesion, including the takeoff of the ICA from the CCA (Figure 1c, 5a). Excessive tortuosity increases the difficulty of access to the lesion, may not permit device delivery, and can prevent distal positioning of an EPD with a “landing zone” sufficient for stent placement. These factors expose the patient to the risks of atheroembolism excessive contrast administration, bifurcation plaque disruption, and ICA dissection. Importantly, tortuosity should be assessed after the sheath (or guide catheter) has been placed in the CCA, because forces by the catheter directed toward the unyielding base of the cranium tend to exaggerate ICA tortuosity (Figure 2). Finally, heavy calcification is an important predictor of complications. This is defined as concentric calcification, <3mm in width and deemed by at least 2 orthogonal views to be circumferentially situated around the lesion (Figure 1d). Heavy calcification, especially in combination with arterial tortuosity, causes difficulties in tracking devices, lesion dilation, stent positioning, and achieving adequate stent expansion. In our experience in more than 1500 cases, the presence of 2 or more of the risk factors listed (Figure 12) is an important adverse prognosticator in patients undergoing carotid stenting. Although special techniques generally result in a satisfactory angiographic outcome, the risk of neurological adverse events exceeds the 3% rule and is thus prohibitive.

 

Figure 13: Factors associated with increased CAS procedural complications.

 

Results
Interpreting Outcomes

Stenting outcomes must be interpreted in an environment of rapidly evolving technology and experience. Procedural outcomes documented 5 years ago are not relevant when considering the expected outcomes with distal embolic protection systems, enhanced-access sheaths, lower profile, more trackable stents, and balloons and adjunctive antiplatelet therapy.

As with any interventional procedure, outcomes are dependent on operator expertise and experience. There is a steep learning curve for physicians beginning carotid stenting. The interventional and clinical skills required for optimal results are not found within the confines of any traditional medical discipline. Neuroradiologists generally lack experience in large vessel intervention, especially stenting, clinical management of patients, and the associated hemodynamic and cardiovascular issues. Cardiologists may have this expertise but lack specific neuroradiology and neuroscience backgrounds. Vascular surgeons and neurosurgeons generally lack the required interventional skills and interventional radiologists often have little experience of carotid vessels and lack the necessary clinical skills. However, over the last decade through interdisciplinary collaboration and focused training, many physicians from diverse disciplines have gained the experience and skills required to produce excellent outcomes from carotid stenting. Choosing an appropriate stenting therapy for each individual patient requires an understanding of the outcomes expected from alternative approaches. It is important to appreciate how rigorously scrutinized carotid stenting results have been compared with surgical therapies. Independent, prospective stroke scale assessment by a neurologist at 24 h was not undertaken in any of the surgical trials. An equally important issue has been the inclusion of patients in early carotid stent series who had never been subjected to rigorous prospective study in endarterectomy trials. The generally low-risk patients studied in NASCET and ACAS (Asymptomatic Carotid Atherosclerosis Study) have only recently been studied in carotid stent series.

 

Thirty-Day Outcomes
Two groups have extensive experience with >1000 cases, and examination of their outcomes, provides insight into the progress that has been made over the last 10 years, in particular the influence of embolic protection devices.

The LHHVI group reviewed completed >1397 carotid stent procedures in 1268 patients (unpublished data). Outcomes were prospectively recorded based on independent neurological examination of the cases within 24 h of the stent procedure. The database was maintained as the group moved from the University of Alabama (Birmingham, AL, USA) to the LHHVI. This large data set is constantly being updated and analyzed to evaluate the outcomes. The data were used to examine the impact of routine use of embolic protection devices and the outcomes that might be expected in various populations of low- and high-risk patients (unpublished data). In this population o 1268 patients, the mean age was 71±9 years and 216 (16%) were aged >80 years. Thirty-four percent were female, 62% had severe coronary artery disease, 16% had undergone prior CEA, and 45% had bilateral carotid disease. Thirty-nine percent had prior symptoms of stroke, transient ischemic attacks, or amaurosis fugax and 61% had high-grade, asymptomatic lesions. First, outcomes since the availability of embolic protection devices in the most recent 551 patients (588 separate vessel–hemispheric interventions) were examined (Table 1). There was a significant reduction in the 30-day incidence of stroke and death, from 6.2% to 2.4%. The difference was seen in both major and fatal strokes (1.5% to 0.6%) and in non-disabling strokes (4.1% to 1.2%).

 

 

Next, the same outcomes were examined in a provocative group of patients aged 380 years who had been treated over the same period. Previous analyses have demonstrated an increased incidence of neurological events in this group [30]. The use of embolic protection devices in this population of patients showed dramatic benefit, with a significant decrease in ischemic complications from 16.5% to 2.3%. The 30-day outcomes were also examined in a group of ACAS-like asymptomatic, low CEA risk patients (Table 2). The current stroke risk in this patient population is 1.1% [6]. Accordingly, when counseling such patients on the relative merits of stenting or endarterectomy, it is possible to demonstrate a stroke risk of 1% without the operative risks of a surgical procedure. The total 30-day rate of stroke and risk from any cause mortality was 1.6%.

 

 

A slight increase was noted in the incidence of retinal embolic events, which were related to the dominant use of distal occlusion embolic protection devices and the potential for directing particles to the ECA. However, these events have not occurred in recent increasing experiences with distal filter systems. Multivariate analysis demonstrated two positive predictors of a procedural stroke during stenting: a history of hypertension and age >80 years. A significant negative descriptor was the use of an embolic protection system. Embolic protection devices, even in their early stages of development, improve outcomes [32–38]. The results are most dramatic in patients at higher risk of events, i.e. the elderly, recently symptomatic patients, and those with severe stenoses and long, bulky lesions. Compared with historical surgical controls, or even the best results reported from endarterectomy, stenting can produce equivalent outcomes without the risk of neck operation, general anesthesia, and the associated complications. In patients at higher risk for CEA, the stent procedure is clearly a safer option [38]. In low CEA risk patients, the stent procedure is as effective and much more acceptable to the patient.

Mathias et al. conducted another large single-center series that confirmed the LHHVI experience. From 1984–98, these authors treated 1222 arteries (hemispheres) with carotid angioplasty and, more recently, stenting without embolic protection (K Mathias, personal communication). The minor stroke rate in this population was 2.1%, with major stroke and death rates of 1.1% and 0.5%, respectively. The total 30-day death and stroke rate was 3.8%. Since 1998, an additional 577 patients have been treated with the inclusion of embolic protection devices, demonstrating a minor stroke rate of 0.9%, a major stroke rate of 0.4%, and a 30-day mortality rate of 0.2%. Thus, the total 30-day stroke and death rate was 1.7%. This group also observed a dramatic reduction in stroke events, from 3.3% to 1.3%, associated with the introduction of embolic protection systems. Of importance was the 0.35% incidence of major disabling stroke in this large series.

CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) was the first prospective, multicenter, randomized trial comparing carotid endovascular intervention with carotid endarterectomy [42]. The interventions were performed by operators in the learning phase of their experience, without the use of embolic protection devices, contemporary appreciation for the use of aggressive antiplatelet therapy, and state-of-the-art stents and ancillary equipment. Only “bail out” stenting was performed (in 26% of patients). While peri-procedural outcomes were higher than would be expected today with distal embolic protection and stenting, they were not different from that observed in the surgical cohort.

SAPPHIRE, the first prospective, randomized, multicenter trial using embolic protection devices, confirmed the utility of stenting compared with endarterectomy, particularly in 307 patients at moderate to high risk from endarterectomy [38]. Severe co-morbidities were common, with 80% having coronary disease, approximately one-third having prior coronary artery bypass grafting and MI, and 20% having CHF, unstable angina, and prior CEA (Figure 14). This first credible “head to head” comparison using contemporary stenting techniques confirmed that for every adverse outcome measure, stenting was safer than endarterectomy. Adverse events included death (0.6% vs. 2%), stroke (3.8% vs. 5.3%), and major ipsilateral stroke (0% vs. 1.3%). The rate of MI was 2.6% vs. 7.3% (p=0.07), and the combined predetermined endpoint of death/stroke/MI was 5.8% vs. 12.6% (p=0.047). In addition, there was a 5.3% incidence of cranial nerve injury in the surgical group and no such injuries in the stent group.

 

Figure 14: CAS in post. CEA restenosis.
a. Post CEA 90% restenosis, proximal and distal.
b. Status post CAS.
c. Control in 23 months.

 

Late Outcomes
Late outcomes after carotid stenting have been consistently favorable and competitive, if not superior, to CEA. Numerous studies have shown that neurological events are rare once the patient has left the procedure room. Rates of late ipsilateral stroke and stroke-related death have been consistent with that seen after endarterectomy. In addition, studies have demonstrated low rates of restenosis by angiographic definition (<5%), with minimal need for re-intervention on the ipsilateral artery (23%) (Figure 15) [37, 43–47].

 

Figure 15: In-stent post CAS restenosis.
a. Symptomatic 60% stenosis (Contralateral ICA occluded-not shown).
b. Status post CAS.
c. 16 months control with significant in-stent restenosis.
d. Status post additional CAS (additional stent placed).

 

Roubin et al. prospectively followed their first 528 consecutive patients treated with carotid stenting over a 5-year period [44,45]. Clinical follow-up was available in 99.6% and ranged from 6 months to 5 years. The authors observed a marked reduction in peri-procedural events over the study period from a 7% minor stroke rate in the first year to 3.1% in the last year (pre-embolic protection devices). Procedural disabling stroke averaged 1% over the study period. Given the dramatic decrease in 30-day events that has occurred over the last 9 years, particularly with the current routine use of embolic protection devices, it was relevant to examine the outcomes after 30 days. In this series, freedom from all fatal and non-fatal ipsilateral strokes was 99±1% at 3 years. Including the 30-day events, the freedom from all fatal and non-fatal ipsilateral strokes was 95±2% at 3 years. Of importance, outcomes were equally favorable for symptomatic and asymptomatic patients in both men and women. It is difficult to compare this data with late outcomes from surgical series since both NASCET and ACAS studied low-risk groups and did not include patients aged >80 years.

Mathias et al. reported 6-month follow-up studies on 1487 treated carotid arteries (K Mathias, personal communication), of which 94% were available for follow-up. The all-cause mortality rate in these patients was 1.8%, and five patients (0.4%) suffered an ipsilateral stroke. The >50% restenosis rate was 4.3%, and, of these patients, 0.5% had complete occlusion. The ipsilateral stroke rate was 2.3%. Gray et al. followed 136 consecutive stent patients and demonstrated a 6-month angiographic restenosis rate of 3.1% and a 100% rate of 2-year freedom from ipsilateral major stroke [46]. Wholey et al. followed their large cohort of patients from Pittsburgh (PA, USA) for a period of 21 months (range 0–5.6 years) (M Wholey, personal communication). Follow-up data were available in 464 patients (94%), in whom the cumulative freedom from stroke or neurological death at 3 years was 96% for self-expanding stents and 95% for balloon expandable stents (early cases), respectively.

The CAVATAS follow-up study confirmed that endovascular treatment had similar major risks and effectiveness at preventing stroke during 3 years compared with CEA [42]. The advantage of endovascular treatment was the avoidance of minor complications related to the neck incision (cranial nerve palsy, hematoma, infections) and use of general anesthesia. Carotid duplex follow-up studies showed more elevated velocities in the non-surgical group, suggesting restenosis. However, angiographic correlations were not performed and the relevance of the elevated velocities and the prognostic implications have been disputed.

One-year follow-up of the SAPPHIRE trial data showed significantly lower rates of death (6.8% vs. 12.6%), major ipsilateral stroke (0% vs. 3.3%), and MI (2.5% vs. 7.9%) without any cranial nerve palsies (0% vs. 4.6%) in the endovascular arm (using the modern stenting technique and embolic protection) in comparison with CEA, thus confirming the results from CAVATAS.

Outcome analyses from multicenter studies strongly suggest that these are applicable to clinical practice. The German Quality Assurance Program (a prospective registry) is a good example of what might be expected with CAS [49]. These data, compiled under the auspices of the German Societies of Angiology and Radiology, prospectively audited outcomes from 35 centers in Germany, Austria, and Switzerland. During the first 30 months, 2142 planned carotid interventions were registered. Of these, 57% were symptomatic and 43% asymptomatic. Stents were used in 98% of patients. Embolic protection systems were introduced as they became available; they were monitored in the last half of the series and were selectively used in 55% of interventions since that time. The overall stroke and death rate was 3%. Individual events included a mortality rate of 0.7%, a major stroke rate of 1.4%, and a minor stroke rate of 0.8%. The investigators concluded that the outcomes represented a realistic view of carotid intervention in the community and suggested that this less traumatic approach represented a realistic alternative to CEA.

 

Future Developments
From a technical perspective, carotid stenting is currently in an extremely rapid phase of development. The ongoing CREST (Carotid Revascularization Endarterectomy vs. Stent Trial) study was initiated with a first-generation embolic protection device, but will soon incorporate second-, third-, and fourth-generation devices. The SAPPHIRE trial was completed using a first-generation embolic protection device and the outcomes of the stenting cohort in that trial are already being questioned given the availability of new technology. Iterative improvements include a lower profile, better tracktability, better particle capture efficiency, and increased ease of retrieval. Embolic protection devices and stents are evolving to include rapid exchange technology that further expedites the procedure. The future will produce carotid stents that contain antiplatelet and antithrombin coatings as well as antiproliferative agents. These devices are already available for use in coronary arteries; however, much work needs to be done to define the optimal adjunctive antiplatelet and anticoagulant therapy for carotid stenting.

Most importantly, interventional experience and expertise with carotid intervention will grow and, as with all medical procedures, the technique will evolve to provide more effective and safer therapy. As the medical management of carotid stenosis progresses, the need for re-evaluation of stenting, and eventually CEA, in comparison with medical therapy will arise. The next major trial should probably compare carotid stenting and CEA with optimal contemporary medical management in asymptomatic patients with moderate carotid stenoses (≤80% diameter). Such a trial, however, should await a collective community experience with stenting in low-risk patients demonstrating a peri-procedural complication rate of ≤2%. There is nothing more important then the proper selection of patients and lesions for CAS, to achieve this goal. We have to distinguish groups of patients not only high risk for CEA, but also the group of patients with high risk for CAS [Figure 11, 12]. In combination with aggressive community based and individual approaches to primary prevention, there is significant potential for this emerging technology to have a profound benefit on stroke prevention. The availability of a much less invasive, patient friendly, outpatient procedure is likely to gain widespread acceptance.



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CV of the author

- Presently works at the Lenox Hill Heart and Vascular Institute of New York. 
- Is a neuroradiologist with special expertise in angiography, interventional procedures specialized in carotid artery stenting.
- Was a professor of Radiology, Neurosurgery and Neurology at University of Alabama School of Medicine in Birmingham till 1997 when he relocated his practice to Lenox Hill Hospital.
- A graduate of Charles University School of Medicine in Czech Republic he practiced neurology and neurosurgery and in 1976 became board certified in radiology.
- Published extensively in peer review national and international journals and was invited as a lecturer to multiple national and international congresses and courses.
- Is a member of multiple national and international Radiological and Neuroradiological societies.

 

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