Author + information
- Received May 2, 2003
- Revision received November 13, 2003
- Accepted November 17, 2003
- Published online April 21, 2004.
- Ravish Sachar, MD*,
- Jay S Yadav, MD*,* (, )
- Marco Roffi, MD†,
- Leslie Cho, MD‡,
- Joel P Reginelli, MD*,
- Alex Aböu-Chebl, MD*,
- Deepak L Bhatt, MD* and
- Christopher T Bajzer, MD*
- ↵*Reprint requests and correspondence:
Dr. Jay S. Yadav, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, USA 44195.
Objectives The study examined the effect of carotid stenting (CS) on contralateral carotid Doppler-defined degree of stenosis.
Background Patients with carotid disease are frequently referred for carotid revascularization (carotid endarterectomy [CEA] or CS) based on the results of carotid duplex studies. Although a drop in flow velocities in the contralateral carotid has been described after CEA, the effect of ipsilateral stenting on contralateral velocities has not been defined.
Methods A total of 104 consecutive patients underwent CS and were divided into two cohorts, those with unilateral stenosis, and those with bilateral stenosis. Doppler-defined pre-procedural peak systolic velocities (PSV) and end-diastolic velocities (EDV) in the contralateral carotid were compared with the post-procedural velocities. Post-procedural angiographic stenoses were compared with post-procedural duplex-defined stenoses.
Results Among patients with bilateral stenosis, after ipsilateral stenting there was a drop in the contralateral PSV and EDV of 60.3 cm/s (p = 0.005) and 15.1 cm/s (p = 0.03), respectively. There was no change in the contralateral velocities in patients with unilateral stenosis. Among patients with ≥60% stenosis by duplex in the contralateral carotid, 20% dropped to a lower classification of contralateral stenosis after ipsilateral stenting. Furthermore, 71% of patients with significant contralateral stenosis by duplex pre-stenting did not have significant stenosis by angiography.
Conclusions Patients with bilateral carotid disease may have elevated Doppler flow velocities in the contralateral carotid resulting in an artifactually high grade of stenosis. After ipsilateral carotid revascularization, such patients should have a repeat Doppler of the contralateral carotid to assess the true grade of stenosis.
Large-scale randomized trials have demonstrated that carotid endarterectomy (CEA) is an effective treatment for the prevention of cerebrovascular events in patients with moderate to severe symptomatic (1,2)and asymptomatic (3)carotid artery stenosis. These results have led to a large increase in the number of CEAs over the past decade (4). More recently, percutaneous carotid artery stenting has been tested as an alternative treatment and has been shown to be beneficial among high-risk patients (5). Patients with carotid disease are frequently referred for carotid revascularization based solely on the results of carotid Doppler studies (6). Although the overall accuracy of carotid Doppler in assessing the severity of the disease is well established (7), the accurate evaluation of patients with severe bilateral carotid stenosis appears to be more problematic. Among patients with severe carotid disease or occlusion, studies have reported an elevation in flow velocities in the contralateral carotid (8–17). The increase in flow velocities in the contralateral carotid has been documented by demonstrating a drop in contralateral flow velocities after ipsilateral CEA (8,9,11). However, the effect of carotid stenting on contralateral flow velocities has not been described. As Doppler criteria for defining stenoses are largely based on flow velocities, elevation of velocities can result in an overestimation of the degree of contralateral stenosis (18,19). This has important clinical implications, as patients may be referred for unnecessary bilateral carotid revascularization.
In this study, we examined the effect of ipsilateral carotid stenting on the peak systolic velocities (PSV) and end-diastolic velocities (EDV) in the contralateral carotid. Additionally, we examined the correlation between the magnitude of decline in contralateral velocities and the degree of pre-existing stenosis.
One hundred four consecutive carotid stent patients who underwent serial carotid ultrasounds at our institution form the basis for this study. Carotid stenting was performed in symptomatic patients if they had ≥70% stenosis, and in asymptomatic patients if they had ≥80% stenosis. All patients underwent carotid stenting after providing informed consent and under an institutional review board protocol. Patients were divided into two groups based on pre-procedural duplex scans. Those with ≥60% stenosis on the contralateral side were classified as bilateralstenosis, and those with <60% on the contralateral side were classified as unilateralstenosis. After carotid stenting, the Doppler velocities in the contralateral carotid were compared with the pre-procedural velocities in the same vessel. The reduction in post-stenting PSV and EDV was used as an estimate of the elevation of pre-stenting flow velocities in the contralateral carotid. Finally, angiograms of patients with bilateral stenosis were reviewed to determine the discrepancy between the degree of stenosis by quantitative carotid angiography (QCA) and the degree of stenosis by Doppler.
All Doppler studies were performed at the vascular laboratory at our institution (accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories). Studies were performed using a hand-held L7.4 MHz or a L12.5 MHz transducer (Advanced Technology Laboratories, HDI 5000, Bothell, Washington) and a sample volume set at 1.5 mm at 60°. The degree of stenosis was defined by a combination of PSV, EDV, and B-mode, using a validated modification of previously described criteria, as shown in Table 1(18,19).
Bilateral carotid angiography was performed using standard techniques with cine angiograms obtained in multiple left anterior oblique and right anterior oblique projections. Hemodynamics and oxygen saturation were continuously monitored, and neurological assessment was performed at regular intervals throughout the procedure. The QCA was performed using the Inturis Suite 2.1.1 (Philips Medical Systems North America, Bothell, Washington).
All data are expressed as means and were analyzed using a two-tailed ttest for two samples assuming unequal variances. Using a linear regression model (SAS Statistical Software, version 8.0, Cary, North Carolina), multivariate analysis was performed to determine the independent predictors of drop in contralateral velocities after stenting.
We studied a total of 104 patients, 49 (47%) with bilateral stenosis and 55 (53%) with unilateral stenosis. The median time between the index procedure and the follow-up Doppler study was nine days (range: 1 to 344 days). The baseline characteristics of patients with unilateral and bilateral disease are shown in Table 2. Approximately two-thirds of the patients in both groups were male, and the mean age was 72 years (range: 56 to 88 years). Coronary artery disease (CAD) was present in 70% of patients (n = 73), 14% (n = 15) had a history of peripheral vascular disease (PVD), and 35% (n = 36) had diabetes mellitus (DM). Approximately 21% (n = 22) had left ventricular (LV) dysfunction (LV ejection fraction ≤35%) and 12% (n = 12) had aortic stenosis. A history of transient ischemic attacks (TIA) and strokes (CVA) was noted in 35% (n = 36) and 23% (n = 24) of all patients, respectively.
Among patients with bilateral stenosis, the mean pre-procedural PSV in the contralateral carotid was 280 cm/s (range: 159 to 647 cm/s, Fig. 1). After ipsilateral stenting, the mean follow-up PSV in the contralateral carotid decreased to 220 cm/s (range: 120 to 547 cm/s) (p = 0.005). Similarly, the mean EDV in the contralateral carotid dropped from a mean of 88 cm/s (range: 35 to 241 cm/s) pre-stenting to a mean of 65 cm/s (range: 8 to 264 cm/s) post-stenting (p = 0.03). In patients with unilateral stenosis, however, there was no significant change in the contralateral PSV or EDV from before to after ipsilateral stenting (Fig. 1). The mean PSV increased from 104.8 to 106.6 cm/s (p = NS), and the mean EDV increased from 30.7 to 31.6 cm/s (p = NS).
When the absolute changes in velocities are examined, a much larger drop in both the PSV and EDV among patients with bilateral stenosis, as compared to patients with unilateral stenosis, becomes evident. Contralateral PSVs decreased an average of 60 cm/s in patients with bilateral stenosis and increased an average of 2 cm/s among patients with unilateral stenosis (p < 0.0001). Similarly, the EDV decreased by an average of 23 cm/s among patients with bilateral stenosis and increased by an average of 1 cm/s among patients with unilateral stenosis (p < 0.0001). In a linear regression model, adjusting for the presence of aortic stenosis, LV dysfunction, PVD, CAD, hypertension, and DM, the presence of contralateral stenosis ≥60% by Doppler prior to stenting was the only independent predictor of a decline in contralateral PSV and EDV after stenting (p < 0.001).
In total, we studied 49 patients with bilateral stenosis. Of these, 10 patients (20%) dropped to a lower classification of stenosis in the contralateral carotid after ipsilateral stenting and, thus, did not subsequently meet the criteria for severe carotid stenosis (Table 3). These 49 patients can be further subdivided into groups of subjects who had moderate (60% to 79%) and severe (80% to 99%) contralateral stenosis by Doppler criteria pre-stenting. The mean drop in PSV and EDV among the severe contralateral stenosis cohort was 70 cm/s and 28 cm/s, respectively, and the mean decline in the PSV and EDV in the moderate contralateral stenosis cohort was 50 cm/s and 19 cm/s, respectively. In the moderate contralateral stenosis group, 12 of the 40 patients (30%), who were initially classified as having significant contralateral stenosis did not fall into this category post-stenting. In the severe contralateral stenosis group, only one of the nine patients (11%) dropped below 60%. The remaining eight patients in the severe contralateral stenosis group remained in the significant stenosis classification.
Of the 49 patients with bilateral stenosis, 44 (90%) had bilateral carotid angiograms performed before ipsilateral stenting. Among the 35 patients in the 60% to 79% contralateral stenosis classification by Doppler pre-stenting, 25 (71%) patients had <50% stenosis by angiography. Among the nine patients with 80% to 99% contralateral stenosis by Doppler, however, only one (10%) had <50% stenosis by angiography, and the remainder had significant angiographic stenosis.
This study examined the effect of carotid stenting on flow velocities in the contralateral carotid among patients with unilateral stenosis and those with bilateral stenosis. Using 60% stenosis as the threshold for significant stenosis, 104 patients were divided into two groups: 55 with unilateral carotid stenosis and 49 with bilateral carotid stenosis. The use of 60% stenosis to define significant carotid stenosis was based on the documented benefit of CEA among asymptomatic patients with ≥60% stenosis (3). After ipsilateral stenting, patients with bilateral stenoses by Doppler criteria experienced a 21% and 26% drop in the contralateral mean PSV and EDV, respectively. This was not noted among patients with unilateral disease. To our knowledge, this is the first study to describe such a decline in contralateral velocities after stenting of the ipsilateral carotid.
In previous studies reporting a drop in contralateral flow velocities after ipsilateral CEA, reduced shunting of blood through the contralateral carotid has been invoked as the mechanism responsible for the decrease in contralateral blood flow (8,9,11). In a study of 386 patients undergoing CEA, Henderson et al. (8)reported a mean drop of 84 cm/s in the contralateral carotid PSV in patients with severe bilateral carotid disease. Consistent with our findings, the decrease in PSV in the contralateral carotid after ipsilateral CEA was inversely proportional to the degree of pre-operative stenosis in the contralateral carotid (8). Busuttil et al. (11)performed Doppler studies before and after CEA in 146 patients and found that 52% of contralateral vessels dropped a level of Doppler-defined stenosis post-operatively. Similarly, Abou-Zamzam et al. (9)showed that CEA resulted in the reclassification of the contralateral carotid stenosis to a lower severity level in 21% of patients with baseline bilateral carotid stenosis. All three investigations attributed the elevation in contralateral carotid velocities in the presence of ipsilateral stenosis to the shunting of flow from the stenosed carotid to the other great vessels. Van Everdingen et al. (10)demonstrated this effect by using magnetic resonance angiography (MRA) to quantify the increase in flow through the contralateral carotid in the presence of high-grade ipsilateral stenosis.
Invoking shunting as the only mechanism to explain the behavior of flow velocities in the carotids, however, is probably an oversimplification. It has been well described that an increase in plaque burden in coronary and carotid arteries is accompanied by a decrease in vascular compliance (20–22). This decrease occurs not only at the site of stenosis but also along the entire vessel, including the common carotid artery (21). A lower compliance results in a reduction of flow-induced vascular dilation and a consequent larger increase in flow velocities in diseased vessels, as compared to disease-free vessels (22). The increase in flow velocities in the diseased contralateral carotid due to lower vascular compliance is probably additive to the increase in velocities due to the presence of a stenosis.
Additionally, it is well known that in disease-free states, there is tight autoregulation of vascular tone in the cerebral vessels. Persistent low-flow states in the cerebral vasculature due to severe bilateral carotid stenosis can result in the loss of this autoregulatory mechanism over time, resulting in chronically dilated intracerebral vessels (23,24). Chronically dilated intracranial vessels can result in a lower intracranial perfusion pressure, and in the presence of severe contralateral disease, this can result in a large gradient across the stenosis in the contralateral carotid. According to the Hagen-Poiseuille equation, as the gradient across the stenosis increases, the velocity will increase proportionally. This may account for the increase in flow velocities observed among patients with contralateral stenosis, but not among patients with unilateral stenosis. Treatment of the ipsilateral stenosis will result in the resumption of autoregulation in the cerebral vasculature over time, thereby attenuating the level of persistent cerebral dilation and decreasing the gradient across the stenosis in the contralateral carotid. Indeed, even the increase in cerebral flow after ipsilateral stenting may increase intracranial perfusion pressure, thereby reducing the gradient across the contralateral carotid. In patients without contralateral stenosis, a gradient across the contralateral carotid would not be expected at baseline, and thus treatment of the ipsilateral stenosis would not be expected to have any effect on contralateral velocities.
Although a large percentage of patients with bilateral disease experienced a drop in contralateral velocities after stenting, this was not a uniform finding. A decline in PSV and EDV was noted among 84% and 75% of patients, respectively, whereas 22 (21%) patients were noted to have no change or an increase in the PSV or EDV after stenting. This has been previously noted among patients after CEA (11)and may be explained by the presence of an extensive cerebral collateral network that would reduce the degree of baseline pre-procedural shunting to the contralateral carotid. In such patients, one would not expect to observe any decrease in contralateral flow velocities after ipsilateral CEA or stenting.
Despite a larger absolute drop in mean PSV and EDV in the contralateral carotid among patients with severe contralateral stenosis (89 cm/s and 37 cm/s, respectively) as compared to patients with moderate contralateral stenosis (55 cm/s and 20 cm/s, respectively), more patients in the moderate stenosis cohort dropped to a lower classification of stenosis after ipsilateral stenting (30% vs. 10%). Furthermore, 71% of patients with moderate contralateral stenosis by Doppler pre-stenting were found not to have significant stenosis by angiography. Among patients with severe baseline contralateral stenosis by Doppler pre-stenting, however, only 10% did not have significant angiographic stenosis. These data suggest that among patients with severe bilateral disease, those with a Doppler-defined severe stenosis in the contralateral carotid before stenting are more likely to have true severe stenosis, whereas those in the moderate stenosis category are more apt to have an artifactually elevated degree of stenosis.
A large number of patients are referred for CEA based solely on the results of a Doppler study without a preceding carotid angiogram. The potential morbidity of carotid angiography—coupled with the demonstrated accuracy of duplex Doppler—has sustained this practice and made it the standard of care (6,7). The present study demonstrates the fallibility of such an approach among patients with bilateral stenosis. These findings are especially pertinent in tertiary-care centers, where the prevalence of bilateral stenosis may be high. In our institution, among 23,151 patients who underwent carotid Doppler studies over the past four years, 8,190 (35%) had severe bilateral disease ≥60% (D. Bossard, unpublished data, 2002).
Based on the results of the present study, patients being referred for bilateral CEAs should routinely have a Doppler study after repair of one side to assess the true stenosis in the contralateral carotid. Only patients found to have severe contralateral stenosis should be referred for CEA, and those with mild to moderate stenosis should be monitored for progression with serial ultrasound studies. Patients with Doppler-defined 60% to 79% disease bilaterally can pose a diagnostic challenge. In such patients, it is difficult to predict which carotid has elevated velocities due to shunting and which one has the true stenosis. One strategy would be to perform carotid angiography on all such patients with bilateral disease prior to CEA. The benefits of such a strategy must be carefully weighed with the potential morbidity of carotid angiography. Noninvasive imaging with MRA or computerized tomography can also be performed to corroborate the degree of stenosis in the contralateral carotid artery without the risk of angiography. Finally, among patients being referred for carotid stenting, routine bilateral carotid angiography often is not performed. As a result, percutaneous interventions are often performed without angiographically assessing the contralateral carotid. Based on our data, bilateral carotid angiography should be performed prior to any percutaneous carotid intervention.
Our study was limited by the small number of patients. There were only nine patients with contralateral stenosis in the 80% to 99% category, and only one of those nine patients dropped to a non-significant range of stenosis. Additionally, although most studies were performed in the first month after stenting, some were performed several months later. Progression of disease in the contralateral carotid during this time cannot be ruled out. Any progression of disease, however, would-only increase flow velocities in the contralateral carotid and, thereby, decrease—not increase—the drop in flow velocities observed after ipsilateral stenting.
Our study demonstrates a significant drop in contralateral velocities after carotid stenting in patients with bilateral severe disease. This finding was not observed in patients who presented with unilateral disease. These data mandate the use of further testing before proceeding with bilateral interventions that are based solely on the results of a single Doppler study.
We acknowledge Katherine J. Lander and Jakob P. Schneider for their help in collating the data.
- coronary artery disease
- carotid endarterectomy
- cerebrovascular accident
- diabetes mellitus
- end-diastolic velocity
- left ventricular
- magnetic resonance angiography
- peak systolic velocity
- peripheral vascular disease
- quantitative carotid angiography
- transient ischemic attack
- Received May 2, 2003.
- Revision received November 13, 2003.
- Accepted November 17, 2003.
- American College of Cardiology Foundation
- ↵Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE). Presented at the annual meeting of the American Heart Association, Chicago, IL, November 2002.
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