OVERVIEW OF ENDOVASCULAR
THERAPY FOR CRANIOCERVICAL DISEASE
Following successful treatment of coronary and peripheral vascular steno-ses, balloon angioplasty of the extracranial cervical vessels was introduced in the late 1970s. It was initially used on an investigative basis for medically refractory, surgically inaccessible lesions in the vertebrobasilar system (1,2) and for multiple or tandem vascular stenoses, such as in Takayasu’s arteritis and in fibromuscular dysplasia (3–6). In recent years, many uncontrolled case series and some registry data have reported reasonable technical suc-cess rates and variable efficacy for stroke prevention. Angioplasty and stent placement have been advocated as viable alternatives to surgery in patients with stenosis of the common and internal carotid arteries who are at high risk of perioperative medical and surgical complications and in other patients for whom endarterectomy may be technically difficult (7–10).
Most data on the safety and benefit of carotid angioplasty and stenting comes from anecdotal reports and observational studies. These data do not substitute for well-conducted, large, randomized trials (11). Reports of out-comes of small series from individual centers are subject to biased assess-ment by the interventionalists, who are usually not blinded. Patients may be preferentially selected, both for the procedure itself and for inclusion in the published report. Conflicts of interest, overt or covert, may exist. Such reports often compare outcomes to historical controls or data from previous trials.
This approach is not sufficiently rigorous to make valid conclusions of effi-cacy because of advances in medical management and differences in case mix and selection criteria between studies.
Endovascular therapy for craniocervical stenosis has inherent attractions.
General anesthesia is not required, which may translate into reduced morbid-ity, particularly in patients with severe cardiac or respiratory disease. It does
not involve a cervical incision, thus eliminating morbidity caused by cervi-cal hematoma and postoperative cranial neuropathies. It may have advan-tages compared to medical therapy for surgically inaccessible lesions in the distal cervical or intracranial carotid or vertebral arteries, for postsurgical restenosis, or for selected technically difficult cases (e.g., radiation stenosis or long stenoses).
However, despite the enthusiasm for endovascular therapy displayed by some advocates, important issues remain to be resolved regarding safety, effi-cacy, and indications for treatment. An expert committee from the Amer-ican Heart Association (12) emphasized several of these. First, an established therapy exists for treatment of severe symptomatic internal carotid artery stenosis. This has considerable benefit (absolute stroke reduction of almost 5% annually) and relatively low complication rates in experienced hands.
To prove benefit, endovascular approaches must demonstrate at least equiva-lent efficacy and risk to endarterectomy in large randomized trials of symp-tomatic patients with severe stenosis.
Second, the risk of stroke associated with diagnostic catheterization of the carotid artery is not trivial (1–3%) and is close to the risk of endarterectomy in some centers. This risk is likely to be higher following manipulation of the plaque.
Third, endovascular therapy has other acute and long-term complications, including bradycardia, cardiac arrest, hypotension, cerebral hyperperfusion injury, and restenosis. The morbidity associated with these problems requires direct comparison with that related to endarterectomy.
Fourth, acute stent thrombosis is not amenable to surgical correction (un-like coronary or limb angioplasty) and is often irreversible despite the use of thrombolytics and glycoprotein IIb/IIIa inhibitors. Also, poststent resten-osis may be difficult or impossible to repair by conventional endarterec-tomy because of the presence of the stent.
Fifth, local or regional anesthesia is increasingly used for carotid endar-terectomy (CEA), and the length of hospital stay is usually not more than 2 days. Therefore, some apparent attractions of endovascular treatment, such as lack of general anesthesia, shorter duration of stay, and lower cost may be more apparent than real.
Finally, few reliable long-term data exist on the efficacy of carotid endo-vascular intervention for stroke prevention.
To date, only one relatively small randomized trial comparing CEA with angioplasty has been completed. Other trials were discontinued prematurely because of higher morbidity in the angioplasty group. At the time of writ-ing, other trials are under way in Europe and the United States. Until these
data are available, there is no reliable evidence supporting the routine use of endovascular stenting for treatment of stenosis of the common or internal carotid artery outside the setting of a clinical trial. For very carefully selected patients (e.g., those with symptomatic carotid disease with a need for coro-nary revascularization, symptomatic restenosis after CEA or neck irradiation, symptomatic vertebral or intracranial carotid stenosis refractory to maximal medical therapy), an endovascular approach may be considered in some centers with experienced operators, providing informed consent is obtained.
UNCONTROLLED STUDIES OF ENDOVASCULAR INTERVENTION FOR CAROTID DISEASE
Most available safety and efficacy data on carotid angioplasty derive from uncontrolled series of patients with extracranial carotid stenosis. In differ-ent case series, the incidence of 30-day periprocedural stroke (minor and major) or death has varied from 0 to 9.7% (13–24). In symptomatic patients with high-grade stenosis (≥90%), the risk of stroke or death has been 4.4–
10.8% within 30 days and 6.8–12.7% over 6–23 months of follow-up. Lower rates have been reported in smaller series (25). In a global carotid stent reg-istry involving more than 5000 patients from 36 centers worldwide, the 30-day stroke and procedure-related death rate was 5.07% (26). Although the risk of all in-hospital medical complications was higher than in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the rates of wound-related complications and perioperative cranial nerve injury were lower.
Reported early technical success rates have been 86–100% (98.4% in the global registry), and the degree of residual stenosis has been reported as min-imal across the studies. Acute stent thrombosis, all asymptomatic, occurred in 2.5% of patients within the first 2 days in one series (15). The duration of hospital stay was usually less than 2 days (14). Ambulatory carotid stenting has also been reported to be safe (27). The incidence of stroke or death dur-ing follow-up (up to 6 years) varied from 0 to 6.9% in two series (15,22).
In a series of more than 500 patients considered high risk for CEA in the opinion of the investigators (71% coronary artery disease, 10% contralateral carotid occlusion, and 83% NASCET ineligible), the technical success rate was 98%, the 30-day rate of stroke or death was 8.1%, and the rate of major stroke or death was 2.6% (28). Symptomatic and asymptomatic patients had similar 30-day outcomes. However, patients 80 years of age or older had significantly higher stroke or death rates. This study suggested that the major-ity of strokes related to carotid angioplasty and stenting take place within the first 30 days, and there is a long-lasting benefit. The incidence of late stroke
(after 30 days, up to 3 years; average 17 months) was 3.2%, only 0.4% of which were major ipsilateral strokes. Although a direct comparison is not possible, these results are in the range reported by NASCET, despite the individuals being considered high risk and NASCET ineligible by the authors (28).
Jordan and coworkers retrospectively compared the risks of stroke and death between endarterectomy and endovascular approaches, both under regional anesthesia, and found that angioplasty and stenting had a signifi-cantly higher stroke or death risk (9.7%) compared to endarterectomy (0.9%).
However, the unusually low risk with endarterectomy in their series, likely related to the use of regional instead of general anesthesia, makes generali-zation difficult (18).
RANDOMIZED CONTROLLED TRIALS
OF ENDOVASCULAR THERAPY FOR CAROTID DISEASE Two early trials comparing endovascular intervention with CEA were stopped prematurely because of excessive morbidity in the endovascular arm.
One of these was discontinued after only 23 patients had been enrolled. In the other trial (WALLSTENT), among 219 patients with symptomatic caro-tid disease (60–90%), 12.2% of those randomized to the stent group had an ipsilateral stroke at 1 year compared to 3.6% of the group who underwent CEA (p = 0.02).
The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVA-TAS) trial randomly assigned 504 patients with symptomatic and asympto-matic stenoses of the common or internal carotid artery who required inter-vention in the opinion of the treating physician (29). The degree of stenosis, calculated by the common carotid method, was greater than 70% in most patients. In an accompanying editorial, Spence and Eliasziw (30) estimated that this corresponded to more than 50% stenosis by the NASCET method, and more than 75% by the European Carotid Surgery Trial (ECST) method.
If these estimates are accurate, the CAVATAS patients comprised a group of symptomatic (96%, about 90% with symptoms in the previous 6 months) and asymptomatic (4%) patients with moderate-to-severe stenosis by the NASCET criteria (mean stenosis 75% by NASCET).
At 30 days, the rates of stroke (>7 days) or death were 10% in the endo-vascular group and 9.9% in the CEA group. Rates of disabling stroke or death were also similar (6.4% in the endovascular and 5.9% in the CEA group).
Although the numbers were small (only 93 followed for 3 years), no differ-ence in stroke rates was detected between groups on follow-up. Severe (>70%) ipsilateral stenosis was more common in the endovascular group at 1 year (14 vs 4%, p < 0.001). However, angioplasty had a much lower rate of cranial neuropathy or hematoma formation.
Spence and Eliasziw compared these results to existing data from large trials that compared CEA to medical therapy (Table 1) (30). Although indi-rect comparisons between studies must be interpreted with caution, they high-lighted several points of concern. Most important was the fact that the rates of stroke and death at 30 days (about 10%) of both surgery and angioplasty or stenting were higher than those reported in the NASCET, ESCT, and Aspi-rin and Carotid Endarterectomy (ACE) trials (average 6.3%). Furthermore, all deaths (seven) in the endovascular group were caused by stroke (three hemorrhagic, four ischemic); only one death in the CEA group was stroke related. This suggests that angioplasty may have directly contributed to the fatal outcomes in this arm.
To benefit patients with moderate symptomatic or asymptomatic disease, intervention-related complication rates must be low (2.3% reported in ACAS).
Based on the stroke or death rates of medically treated patients in these trials, neither endarterectomy nor endovascular therapy in CAVATAS was likely to have provided a meaningful benefit for patients with moderate sympto-matic or asymptosympto-matic disease. The 30-day rates of stroke (>7 days) or death in CAVATAS (10%) are almost identical to the rates at 3 years for medically Table 1
Indirect Comparisons of Major Endarterectomy Trials with CAVATAS
3-Year 3-Year
stroke or stroke or 30-Day
death risk if death risk of Risk Number periprocedural medically intervention difference needed to stroke or
treated (%) (%) (%) treat death (%)
Symptomatic severe 25.1 8.9 16.2 6 5.8
NASCET (70–99%)
Symptomatic severe 16.8 10.3 6.5 15 7.5
ECST (70–99%)
Symptomatic moderate 16.2 11.3 4.9 20 7.1
NASCET (50–69%)
Asymptomatic 11 5.1 5.9 19 2.3
moderate–severe ACAS (60–99%)
CAVATAS (CEA) 18.6a 13.9 4.7 21 9.9
CAVATAS 18.6a 14.4 4.2 24 10
(angioplasty or stent)
Source: From data summarized in refs. 29 and 30.
aNo medical arm. Medical risk was calculated from a weighted average of medical arms from NASCET and ECST studies (30).
ACAS, Asymptomatic Carotid Atherosclerosis Study.
treated asymptomatic patients (11%); there was no evidence to indicate ben-efit in this group. On the contrary, at 3 years more asymptomatic patients in CAVATAS had suffered stroke or death than similar medically treated patients in ACAS (14.4 vs 11%), suggesting that early events may have been precipi-tated as a result of the intervention. Comparing the rates of stroke (>7days) or death at 3 years in CAVATAS with those in NASCET for symptomatic patients with moderate stenosis, the benefit of angioplasty was negligible (absolute risk difference 1.8%, number needed to treat 56). Based on the clinical characteristics of subjects included in CAVATAS , it is unlikely that case mix accounts for these differences in outcome.
Other randomized, multicenter trials are ongoing. These include the Inter-national Carotid Stenting Study (ICSS) (31), Carotid Revascularization–
Endarterectomy vs Stent Trial (CREST) (32), and Carotid Artery Revascu-larization With Endarterectomy or Stenting Systems (CARESS) (33). It is anticipated that these studies will resolve some of the issues discussed here.
POTENTIAL INDICATIONS
FOR CRANIOCERVICAL ANGIOPLASTY OR STENTING Risk Stratification for CEA and Endovascular Therapy
A list of potential indications for craniocervical endovascular therapy is presented in Table 2 based on data from uncontrolled studies and the absence of safe alternative treatments (12,34).
Several groups have examined potential predictors of adverse outcome after CEA and endovascular therapy. Mathur et al. (35) reported that age was associated with higher risk for neurological events associated with angio-plasty and stenting; age older than 80 years had an overall stroke incidence of 19.2%. Long or multiple stenoses or severe lesions (>90% stenosis) carried a significantly higher risk for stroke in univariate analysis. In multivariate analysis, only age (odds ratio [OR] 1.1) and long and tandem stenoses (OR 5.1) were significantly associated with a higher risk of periprocedural stroke.
Qureshi and colleagues reported an increased the risk of neurological com-plications with symptomatic lesions (OR 8.3), with a stenosis longer than 11.1 mm (OR 5.3), and absence of hypercholesterolemia (OR 5.4) (36).
Risk Prediction Based on Medical, Neurological, and Angiographic Factors
Sundt and coworkers proposed a grading system for risk stratification of CEA (37). They defined potential medical risk factors as angina pectoris or recent (<6 months) myocardial infarction (MI), congestive heart failure, blood pressure exceeding 180/110, chronic obstructive lung disease, age older than
70 years, and severe obesity. Neurological risk factors were defined as pro-gressing neurological deficit, stable recent deficit (<24 hours from onset), frequent daily transient deficits, and deficits secondary to multiple cerebral infarcts. Potential angiographic risk factors were defined as contralateral carotid occlusion, siphon stenosis, long diseased segment, high carotid bifur-cation, and soft thrombus over the plaque.
In a retrospective analysis of a relatively small cohort who underwent CEA, neurologically stable patients with no medical comorbidity with (grade II) or without (grade I) angiographic risk factors had 1–2% risk of developing myo-cardial infarction or persistent postoperative neurologic deficits. Patients with medical comorbidities without neurological risk factors (grade III) had a 7% risk of developing myocardial infarction. Of those with neurological risk factors, regardless of their medical or angiographic risks (grade IV), 10% had stroke associated with CEA.
Sieber et al. reported that the total morbidity (MI, stroke) and mortality from CEA increased from about 2% for grade I, to 10% for grade II, 11%
for grade III, and 18% for grade IV (38). The incidence of MI was highest in group III. Stroke was more common in groups II and IV, with worse out-come in the latter group (39). This study, therefore, suggested an associa-tion between angio-graphic risk factors and increased incidence of stroke.
In a large multicenter retrospective review (39), the presence of two or more proposed Sundt predictors was associated with a 1.7 times higher risk of stroke, MI, or death and twice the risk of stroke or death.
There is yet no published randomized trial comparing CEA and endovas-cular approaches in high-risk patients. However, small uncontrolled series have suggested lower morbidity and mortality associated with angioplasty or stenting. For example, Al-Mubarak et al. reported a major stroke or death Table 2
Potential Indications for Craniocervical Endovascular Therapy
1. Patients at high risk for CEA with progressive/recurrent neurological symp-toms and who are unresponsive to maximal medical therapy (e.g., unstable coronary disease, heart failure)
2. Restenosis after endarterectomy or angioplasty 3. Radiation-induced stenosis
4. Patients with surgically inaccessible lesions, with progressive or recurrent neurological symptoms, unresponsiveness to maximal medical therapy (high cervical, intracranial carotid, vertebrobasilar stenosis)
Source: From ref. 34.
rate of 4.5% in 44 Sundt grade IV patients, with good intermediate-term arterial patency (40). Similarly, in patients with high medical risks, the 30-day procedural risk of stroke or death was 2.9%. Of these, 76% were ineligi-ble for CEA by NASCET criteria (53% < 80 years, 26% had left ventricular ejection fraction ≥30%, and 44% had moderate-to-severe angina) (41). Com-bined carotid and coronary interventions have also been well tolerated (41, 42). In patients with contralateral carotid occlusion the 30-day risk of stroke and death was zero after angioplasty and stenting in a small case series (43), compared to 14.3 % after CEA in NASCET (44).
Endovascular Approaches
for Restenosis and Radiation-Induced Stenosis
Post-CEA restenosis renders repeat endarterectomy technically difficult because of scarring. Surgery for recurrent stenosis has been reported to carry a 10% risk of death or major neurologic complications (45), the latter mostly in symptomatic patients who had intraluminal thrombus. The risk was 11%
in those patients with medical risk factors and recurrent stenosis (38). In a series of 22 patients who had angioplasty and stenting for recurrent stenosis after CEA, the procedure was successful in all, with only one minor pro-cedural stroke. There were no ipsilateral neurological events over a mean follow-up of 8 months. None of the patients had angiographic restenosis of 50% or more at 6 months, and mean restenosis was 19% (46). In another series of patients who had angioplasty with or without stenting for recurrent carotid stenosis following CEA, Lanzino et al. reported no major peripro-cedural stroke or death. Patients remained asymptomatic for a mean follow-up of 27 months. More than 50% restenosis developed in 60% of patients treated with angioplasty alone and in only 5.6% of the vessels treated by combined angioplasty and stent placement (47). Finally, in a larger series of restenosis following endarterectomy, the 30-day stroke and death rate was 3.7% (48).
Cervical irradiation predisposes the involved arteries to accelerated steno-sis because of destruction of the internal elastic lamina and myointimal hyper-plasia (49). These stenoses have a predilection for the distal common carotid artery after cervical irradiation. Although patients are often younger com-pared to those with atherosclerotic stenosis, the lesions involve longer seg-ments of the artery and often show circumferential narrowing of the lumen.
In a series of 14 patients who had stent placement for radiation-induced caro-tid stenosis, only one minor stroke happened with full recovery; there was no restenosis of 50% or more at 6-month follow-up (50). Others have reported similar results (51).
Intracranial Anterior and Posterior Circulation Stenoses
Intracranial stenoses are estimated to account for 5–10% of all ischemic strokes and transient ischemic attacks (52–57). The cavernous portion of the internal carotid artery is the most common location of anterior circulation stenosis, followed by the petrous and clinoid carotid (55) and the proximal middle cerebral artery. The recommended treatment strategy for symptoma-tic intracranial stenosis is antiplatelet therapy and other secondary prevention measures. Randomized trials are required to evaluate the role of angioplasty and stenting for symptomatic intracranial disease. In the absence of such trials, endovascular approaches may have a role for selected cases if recur-rent or progressive neurological symptoms are occurring despite maximal medical measures.
Factors that should be considered when selecting such patients for inter-vention include (1) the accessibility, length, degree, and eccentricity of the stenosis; (2) the presence of other lesions (contralateral occlusion, tandem stenoses); (3) the intracranial hemodynamic status assessed by positron emis-sion tomography or other techniques; and (4) the experience of the perform-ing center.
COMPLICATIONS OF ANGIOPLASTY AND STENTING Stent Thrombosis and Distal Embolization
Acute thrombosis and embolism to the brain is the most common cause of periprocedural neurologic morbidity. Severe dissection and acute closure of the artery carry the highest risk (14). Predisposing factors for thromboem-bolic complications of angioplasty and stenting have not been defined. How-ever, data from small case series suggest that pre- and poststent combination antiplatelet coverage reduces stent thrombosis (58).
Platelet activation has been demonstrated in coronary stenting, in which, in addition to dual antiplatelet therapy with aspirin and either clopidogrel or ticlopidine (59), periprocedural intravenous abciximab (a platelet glycopro-tein IIb/IIIa receptor antagonist) reduces the rate of ischemic complications.
In one small series of carotid stent placement, abciximab was associated with a lower rate of periprocedural stroke without an increase in the risk of intracranial hemorrhage compared to historical controls (60). A few reports have described successful recanalization with intraarterial, followed by intra-venous, abciximab following acute stent occlusion (61). Therefore, abciximab appears to be a promising prophylactic as well as therapeutic agent against ischemic events during angioplasty and stenting when used in combina-tion with heparin, low-dose thrombolytics, aspirin, and clopidogrel (62,63).
Similarly, another glycoprotein IIb/IIIa receptor antagonist, eptifibatide (135 µg/kg bolus followed by infusion at 0.5 µg/kg per minute), has been shown to be safe during carotid angioplasty and stenting in a small phase I study (64).
Balloon inflation times of 15–30 seconds during carotid angioplasty have been well tolerated (14). Both CEA and angioplasty with stenting are asso-ciated with complete interruption of blood flow during shunt insertion or balloon inflation. The duration of blood flow reduction and ischemia appears to be shorter for angioplasty (less than 0.5 minutes) compared to endarter-ectomy (longer than 2.5 minutes) (65,66). On the other hand, four to eight times more microembolic signals were observed during angioplasty com-pared to endarterectomy; the pre- and postdilation and stent deployment phases have been associated with high frequency of microembolic signals (66–68). Some of the microembolic signals observed during angioplasty are likely to be microscopic air bubbles associated with contrast injection and therefore of little clinical significance. However, the majority of microem-boli consist of cholesterol crystals, lipoid masses, and fibrin material, with sizes between 1 µm and 5 mm (mean about 300 µm) (69–71).
There are conflicting data regarding the clinical importance of flow reduc-tion during occlusion as well as the number of microembolic signals. In some studies, neither the duration of occlusion nor the number of microemboli have been related to either the periprocedural stroke risk or long-term neuro-psychological outcome (66,72–74). However, using transcranial Doppler (TCD) during occlusion, others have found an increased risk of periproce-dural transient ischemic attack and stroke when the mean middle cerebral artery blood flow velocity is reduced by 50% or more (75). Similarly, in a series of 84 patients for whom a distal filter protection device was used, there was only one minor (1.2%) and no major periprocedural neurological event or procedure-related death (69). Distal balloon protection devices may reduce the number of microembolic signals on TCD by more than 50% (68). These devices are rapidly gaining favor and appear to reduce the periprocedural neurologic event rate (76,77). Again, randomized trials are required to deter-mine their efficacy and safety.
Restenosis
Late restenosis has been a major concern following angioplasty. Although more widespread use of stenting has reduced the reported incidence of restenosis (47), rates vary widely. Degrees of restenosis (>60–70%), mostly asymptomatic, were seen in 0–25% of patients on long-term follow-up after stent angioplasty in different series (13–15,19,30,41). The average degree of restenosis was 12–18% at 6 months (13,14,41). In CAVATAS, stenting
did not appear to reduce restenosis (severe stenosis or occlusion was seen in 22% of patients who received a stent vs 17% of patients who had angioplasty alone), although the number of stented cases was low (n = 41) (29).
About half of restenoses after angioplasty with or without stenting have been estimated as caused by recurrent atherosclerosis, one-fourth caused by neointimal hyperplasia, and the rest caused by the presence of organized thrombus (45). Recurrent atherosclerosis is characterized by lipid deposits and lipid-laden macrophages (foam cells), whereas neointimal hyperplasia predominantly involves smooth muscle cell proliferation and migration.
Neointimal hyperplasia after coronary angioplasty has been associated with a smooth plaque surface. Therefore, neointimal hyperplasia after carotid angioplasty may be less likely to cause artery-to-artery embolism. In these cases, symptoms may be primarily related to hemodynamic insufficiency (78).
Mechanisms of restenosis and potential preventive measures have been subjects of intense investigation. Among the promising approaches, nitric ox-ide and cytostatic agents have attracted particular attention. Increased nitric oxide/cyclic guanosine 5'-monophosphate signaling by supplemental L-argi-nine or nitric oxide synthase gene transfer reduces neointima formation after stenting via a mechanism dependent on nitric oxide synthase (79). Drugs that inhibit cell proliferation at different levels, such as paclitaxel (antimitotic), sirolimus (inhibits cell division between phases G1 and S1), cytochalasin D (inhibits actin filament formation), and phosphorothioate oligodeoxynucle-otides have been shown to halt neointimal hyperplasia when delivered locally in experimental animals (80–83). However, further work is needed before these approaches find clinical use in prevention of restenosis.
Hyperperfusion Syndrome
Hyperperfusion syndrome occurs in about 1% of patients after CEA (84).
A sudden increase in cerebral perfusion pressure to a previously ischemic vascular territory with impaired autoregulation predisposes to cerebral edema formation and intracerebral or subarachnoid hemorrhages. The usual presenting features are headache, vomiting, altered mental state, focal neuro-logic deficits, hypertension, and seizures. Hyperperfusion syndrome has been associated with internal carotid, vertebral, or middle cerebral artery angio-plasty and stenting (85–87). In one series, it was reported in 5% of patients following cerebral angioplasty or stenting (88). This number is higher than that after endarterectomy and requires verification by other investigators.
Angioplasty and stenting of major cerebral arteries immediately augments angiographic cerebral blood flow (89–92) and normalizes oxygen extraction fraction (92,93) as well as cerebrovascular reactivity (90,94). However,
per-sistently increased cerebral blood flow above normal levels (likely because of failure of cerebral vasculature to autoregulate and buffer quickly the rise in perfusion pressure) may be a marker of hyperperfusion syndrome (86,88).
Reported predictors of hyperperfusion syndrome after CEA are high-grade stenosis (>80%) with significant pressure gradient, poor collateral flow or contralateral carotid occlusion, perioperative hypertension, and the use of anticoagulation or antiplatelet agents (95–101). Although factors associated with hyperperfusion syndrome after angioplasty are unknown, a profile simi-lar to CEA would be expected. Strict blood pressure control is the mainstay of management, and TCD monitoring of flow velocities and pulsatility index has been used to titrate the mean arterial pressure level (102).
Hypotension and Bradycardia
The problems of hypotension and bradycardia are relatively common after carotid angioplasty or stenting involving the carotid sinus (103). They can occur immediately after balloon inflation because of stimulation of carotid sinus baroreceptors, simulating a sudden increase in intraarterial pressure.
This culminates in increased vagal output and reduced sympathetic tone and may persist for many hours after the procedure. In one series, 71% of patients had transient bradycardia during balloon inflation (14). In another, 70% of patients developed bradycardia, 56% became hypotensive, and 27% had asys-tole (13). In a retrospective analysis, patients who developed hypotension with bradycardia during the procedure were at higher risk for doing so after the procedure for up to 24 hours (104). Furthermore, patients who had a history of myocardial infarction were also at higher risk for developing postprocedural hypotension. Angioplasty-induced bradycardia appears to be more preva-lent in radiation-induced stenosis and with symptomatic lesions. The proper management requires prompt recognition, fluid resuscitation, pharmacologi-cal pressors, and temporary venous demand pacing (105). Atropine (1 mg iv) can be administered as needed during balloon inflation.
Complications of Intracranial Angioplasty
Complications of intracranial angioplasty are similar to those encountered with endovascular intervention of the extracranial vessels and include arterial dissection, rupture, spasm, acute thrombosis, and distal embolization (106, 107). The introduction of stents has reduced arterial dissection, spasm, and immediate elastic recoil (108–111). Improved technical details such as slow balloon inflation and the use of balloons smaller than the normal diameter of the artery have reduced complications such as dissection and acute vessel closure (112). Acute dissection of the artery during angioplasty can be treated
with a stent in selected patients (113,114), whereas arterial spasm often responds to intraarterial vasodilator infusions. Anticoagulation and platelet glyco-protein IIb/IIIa antagonists during and after the procedure reduce the inci-dence of distal embolization and thrombosis. One often feared complication of stenting has been the occlusion of penetrating arteries that take off from the main artery, either by the stent (so-called jailing) or by debris from the crushed atherosclerotic plaque during balloon inflation; however, this has not been a frequent complication in clinical studies to date (115–117).
REFERENCES
1. Sundt TM, Smith HC, Campbell JK, Vlietstra RE, Cucchiara RF, Stanson AW.
Transluminal angioplasty for basilar artery stenosis. Mayo Clin Proc 1980;55:
673–680.
2. Motarjeme A, Keifer JW, Zuska AJ. Percutaneous transluminal angioplasty of the vertebral arteries. Radiology 1981;139:715–717.
3. Hasso AN, Bird CR, Zinke DE, Thompson JR. Fibromuscular dysplasia of the internal carotid artery: percutaneous transluminal angioplasty. AJR Am J Roent-genol 1981;136:955–960.
4. Belan A, Vesela M, Vanek I, Weiss K, Peregrin JH. Percutaneous transluminal angioplasty of fibromuscular dysplasia of the internal carotid artery. Cardiovasc Interv Radiol 1982;5:79-81.
5. Dublin AB, Baltaxe HA, Cobb CA 3rd. Percutaneous transluminal carotid angio-plasty in fibromuscular dysplasia. Case report. J Neurosurg 1983;59:162–165.
6. Wilms GE, Smits J, Baert AL, De Wolf L. Percutaneous transluminal angioplasty in fibromuscular dysplasia of the internal carotid artery: 1 year clinical and mor-phological follow-up. Cardiovasc Interv Radiol 1985;8:20–23.
7. Bockenheimer SA, Mathias K. Percutaneous transluminal angioplasty in arterio-sclerotic internal carotid artery stenosis. AJNR Am J Neuroradiol 1983;4:791–792.
8. Wiggli U, Gratzl O. Transluminal angioplasty of stenotic carotid arteries: case reports and protocol. AJNR Am J Neuroradiol 1983;4:793–795.
9. Kachel R, Basche S, Heerklotz I, Grossmann K, Endler S. Percutaneous trans-luminal angioplasty (PTA) of supra-aortic arteries especially the internal carotid artery. Neuroradiology 1991;33:191–194.
10. Numaguchi Y, Puyau FA, Provenza LJ, Richardson DE. Percutaneous transluminal angioplasty of the carotid artery. Its application to post surgical stenosis. Neuro-radiology 1984;26:527–530.
11. Brott TG. Angioplasty and stenting should be performed only in the setting of a clinical trial. Stroke 2002;33:2519–2520.
12. Bettmann MA, Katzen BT, Whisnant J, et al. Carotid stenting and angioplasty: a statement for healthcare professionals from the Councils on Cardiovascular Radiology, Stroke, Cardio-Thoracic and Vascular Surgery, Epidemiology and Pre-vention, and Clinical Cardiology, American Heart Association. Stroke 1998;29:
336–338.
13. Gil-Peralta A, Mayol A, Marcos JR, et al. Percutaneous transluminal angioplasty of the symptomatic atherosclerotic carotid arteries. Results, complications, and follow-up. Stroke 1996;27:2271–2273.
14. Yadav JS, Roubin GS, Iyer S, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:376–381.
15. Dietz A, Berkefeld J, Theron JG, et al. Endovascular treatment of symptomatic carotid stenosis using stent placement: long-term follow-up of patients with a bal-anced surgical risk/benefit ratio. Stroke 2001;32:1855–1859.
16. Diethrich EB, Ndiaye M, Reid DB. Stenting in the carotid artery: initial experi-ence in 110 patients. J Endovascr Surg 1996;3:42–62.
17. Dietrhrich EB. Indications for carotid artery stenting: a preview of the potential derived from early clinical experiences. J Endovasc Surg 1996;3:132–139.
18. Jordan WD Jr, Voellinger DC, Fisher WS, Redden D, McDowell HA. A compari-son of carotid angioplasty with stenting vs endarterectomy with regional anesthe-sia. J Vasc Surg 1998;28:397–402; discussion 402–403.
19. Malek AM, Higashida RT, Phatouros CC, et al. Stent angioplasty for cervical caro-tid artery stenosis in high-risk symptomatic NASCET-ineligible patients. Stroke 2000;31:3029–3033.
20. Henry M, Amor M, Masson I, et al. Angioplasty and stenting of the extracranial carotid arteries. J Endovasc Surg 1998;5:293–304.
21. Roubin GS, Yadav S, Iyer SS, Vitek J. Carotid stent-supported angioplasty: a neu-rovascular intervention to prevent stroke. Am J Cardiol 1996;78:8–12.
22. Pappada G, Marina R, Fiori L, et al. Stenting of atherosclerotic stenoses of the extracranial carotid artery. Acta Neurochir 2001;143:1005–1011.
23. White CJ, Gomez CR, Iyer SS, et al. Carotid stent placement for extracranial caro-tid artery disease: current state of the art. Catheterization & Cardiovascular Inter-ventions 2000;51:339–346.
24. Rosenwasser RH, Shanno GB. Angioplasty and stenting for carotid atheroscle-rotic disease. Neurosurg Clin N Am 2000;11:323–330.
25. Guterman L, Hopkins N. Carotid Angioplasty and Stenting. Philadelphia: Ameri-can Association of Neurological Surgeons, 1998.
26. Wholey MH, Wholey M, Mathias K, et al. Global experience in cervical carotid artery stent placement. Catheter Cardiovasc Interv 2000;50:160–167.
27. Al-Mubarak N, Roubin GS, Vitek JJ, New G, Iyer SS. Procedural safety and short-term outcome of ambulatory carotid stenting. Stroke 2001;32:2305–2309.
28. Roubin GS, New G, Iyer SS, et al. Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery steno-sis: a 5-year prospective analysis. Circulation 2001;103:532–537.
29. CAVATAS investigators. Endovascular vs surgical treatment in patients with caro-tid stenosis in the Carocaro-tid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet 2001;357:1729–1737.
30. Spence D, Eliasziw M. Endarterectomy or angioplasty for treatment of carotid ste-nosis. Lancet 2001;357:1722–1723.
31. Brown MM. Angioplasty and stenting. Adv Neurol 2003;92:335–345.
32. Hobson RW 2nd. Update on the Carotid Revascularization Endarterectomy vs Stent Trial (CREST) protocol. J Am Coll Surg 2002;194(1 Suppl):S9–S14.
33. Roubin GS, Hobson RW 2nd, White R, et al. CREST and CARESS to evaluate carotid stenting: time to get to work! J Endovasc Ther 2001;8:107–110.
34. Chaturvedi S, Ressler R. Angioplasty and stenting for stroke prevention. Neurol-ogy 2002;59:664–668.