Predictors of Difficult Carotid Stenting as Determined by<br />
Aortic Arch Angiography

Stroke is the third major cause of death in the United States with carotid artery occlusive disease as the underlying etiology in about 20–30% of cases.^1,2 Carotid artery stenting (CAS) is a widely used procedure for carotid artery occlusive disease, especially in patients at high risk for carotid endarterectomy.^3,4 CAS is a less invasive procedure than carotid endarterectomy, but it is not free from risk. The risk of permanent neurological deficit because of diagnostic cerebral angiography alone is considerable and estimated to be about 1%.^5–7 The effectiveness of carotid stenting in preventing stroke depends on the ability of the operator to achieve minimal complications.⁸ The local anatomic and lesion factors increase the fluoroscopy time and risks associated with CAS,^9,10 whereas systemic factors and comorbidities increase the risks associated with carotid endarterectomy.³ The aortic arch anatomy in particular plays an important role in determining the success of the procedure. There are few classifications that categorize aortic arch anatomy, but literature on their impact on procedural complexity and outcome is scarce and has not been well established.^11–13 The purpose of this study was to evaluate the impact of aortic arch anatomy in predicting the fluoroscopy time in patients undergoing CAS.

Methods
All patients undergoing CAS at our institution are prospectively followed and data are entered in a registry based on a protocol approved by the institutional review board. The details of this registry have been previously published.^14,15 From this registry, we selected patients who underwent CAS from 1998 to 2005. Patients were then sorted into deciles based on the fluoroscopy time and were categorized into difficult CAS (top decile) or easy CAS (bottom decile). We chose fluoroscopy time (time from achieving vascular access until the final selective postinterventional angiogram) as the outcome of interest since it eliminates any delay due to logistic problems not related to procedural complexity.¹⁶ We excluded patients who did not undergo carotid angiography to define their aortic arch anatomy as well as patients who had a delay in their procedure due to difficult access or intraprocedural complications (such as hypotension, transient ischemic attack or stroke). This allowed us to select patients in whom the fluoroscopy time was more likely to be related to CAS difficulty secondary to the anatomy of the vessels. We then extracted demographic and angiographic information on study patients from our CAS registry and reviewed patients’ charts for data relating to clinical presentation, laboratory results and comorbidities.

Aortic arch angiograms are taken in the left anterior oblique view (LAO) using a 5 Fr pigtail side-hole catheter with injection of dye to opacify the aortic arch and supraaortic vessels as far as the skull base. Angiographic variables related to the anatomy of the aortic arch and carotid arteries were then measured from recorded arch angiograms using Image J software (https://rsb.info.nih.gov) as shown in Figure 1. The vertical distance from the origin of the innominate artery to the top of the arch determines the arch type. This distance is < 1 diameter of the left common carotid artery (CCA) in a Type 1 arch, between 1 and 2 CCA diameters in a Type 2 arch, and > 2 CCA diameters in a Type 3 arch (Figure 2).¹³ Other anatomic characteristics assessed were lesion site, severity of the stenosis, tortuosity (T) of the target vessels, distance from the origin of the treated artery to the beginning of the descending aorta (D1), vertical distance from the top of the arch to the origin of the target vessel (D2), angulated takeoff of the vessel (≤ 30 degrees between the aortic arch and the innominate artery [for right-sided lesions] or left CCA [for left-sided lesions]), index lesion calcification, ulceration and eccentricity. Severe stenosis was defined as luminal angiographic stenosis ≥ 95%, and severe tortuosity was defined as a > 60-degree angulation from the center-line flow of blood for either the CCA or the internal carotid vessel on the side of the CAS.¹¹

Carotid artery stenting technique. After local anesthesia to the groin, access via the common femoral ar tery was obtained. Each patient was appropriately anticoagulated following sheath placement. Diagnostic angiography with arch angiography was performed to precisely measure the stenosis and diameter of the distal internal carotid artery (ICA) and accurately size the balloons and stents required to perform the procedure. The use of a guidewi re- or sheath-based approach was left to the operator’s discretion. With the use of a standard coaxial system, the lesions were crossed using an embolic protection device (EPD). Very severe lesions were predilated using lowprofile coronary balloons. Once the EPD or guidewire was in place, the stent was introduced under fluoroscopic guidance. The stent was correctly positioned and deployed and was further dilated at high pressure (8 to 14 atm) to firmly embed it in the vessel wall. Follow-up angiography was performed on the ipsilateral intracranial vessels.
Statistical analysis. Differences between the demographics, clinical characteristics and angiographic variables of patients with difficult and easy CAS were determined by Fisher’s exact test for categorical variables and the Student’s t-test or Mann-Whitney U-test for continuous variables. Variables that appeared to be imbalanced between the two groups, as indicated by a p-value < 0.2, were incorporated into the multivariable models. A backward stepwise approach was used to determine the variables that independently predicted prolonged fluoroscopy time. The Hosmer-Lemeshow goodness-of-fit statistic was used to evaluate the fit of the final model.¹⁷ The level of significance was set at 0.05 and analyses were performed using SPSS Statistical Software, Version 9.0 (SPSS, Inc., Chicago, Illinois).

Results

Baseline characteristics. From a total of 71 patients in the difficult CAS group, we excluded patients who did not undergo arch angiography (n = 33) and those who had intraprocedural adverse events (n = 14). Similarly, from a total of 75 patients in the easy CAS group, we excluded patients who did not undergo arch angiography (n = 38) and those who had intraprocedural adverse events (n = 13). Therefore, we were left with 24 patients in each CAS group. The two CAS groups were similar in demographic characteristics, comorbidities and clinical presentation (Table 1).
Angiographic characteristics and fluoroscopy time. Table 2 summarizes the angiographic characteristics of the study population. The median fluoroscopy time was 19.1 minutes for the easy CAS group versus 58.1 minutes for the difficult CAS group (p < 0.0001). Embolic protection devices were used in all but 2 cases, with a self-expanding stent placed in all patients. The choice of devices depended on their availability in the laboratory and operator discretion. As shown in Table 2, univariate analysis did not show any significant difference in the two groups with respect to the vertical distance (D2) from the top of the arch to the origin of the target vessel site of the lesion, severity of stenosis, blocked external carotid artery (ECA) or index lesion calcification, ulceration and eccentricity. Patients with difficult procedures had a longer distance from the origin of the treated artery to the beginning of the descending aorta (D1; 50 ± 17 mm vs. 40 ± 16 mm; p = 0.04), severe tortuosity of the CCA and internal carotid vessels (T; 50.0% versus 16.7%; p = 0.03) and a trend in the presence of a Type 3 arch (33.3% vs. 25.0%; p = 0.18) and angulated takeoff (20.8% vs. 4.3%; p = 0.19).
Six variables with p-values < 0.2 from univariate analysis were included for multivariate analysis. A backward stepwise approach eliminated Type 3 arch, angulated takeoff, gender and history of carotid endarterectomy, leaving D1 (odds ratio 1.04 per mm; 95% CI, 1.01–1.09; p = 0.04) and T (odds ratio 4.77; 95% CI 1.3–42.9; p = 0.03) as the significant predictors of prolonged fluoroscopy time in the final model (Nagelkerke R square, 0.32). The Hosmer-Lemeshow goodness-of-fit statistic for the final model was 5.73 on 7 degrees of freedom, indicating a good fit for the data (p = 0.57).

Discussion
The primary objective of this study was to identify anatomic characteristics that predict technically challenging CAS requiring prolonged fluoroscopy time. Our study revealed that the horizontal distance between the onset of the arch of the aorta and the treated vessel and the tortuosity of target vessels were important factors predicting the fluoroscopy time, while lesion severity, calcification, type of lesion (concentric or eccentric) and the blocked ECA did not have any significant impact on fluoroscopy time.
Coronary stenting has a well-defined scoring system according to the patient’s coronary anatomy that defines complex procedures, such as A, B and C lesions. This system helps the operator assess the difficulty of the procedure and plan the treatment strategy accordingly.¹⁸ In carotid artery stenting, no such well-defined classification exists. Limited literature published on carotid arch anatomy has found that certain arch anomalies are associated with procedural complexity and technical failure.¹² Some anomalies such as bovine arch can occur in as many as 10% of patients and can lead to increased neurological complications after CAS.¹² Another study has shown that the majority (73.1%) of technical failures during CAS are due to tortuosity or angulations of the aortic arch and of the CCA.¹¹ These anatomical characteristics are also more common in the elderly, likely due to increased vessel elongation over time, and this may account for the higher CAS failure rate seen in octogenarians.^11,19

Our findings are consistent with the published studies that have reported the association of significant kink, tortuosity and angulated takeoff of the ICA with technical difficulties in CAS.^9,11,20 Complex arch anatomy such as tortuosity requires precise wire and catheter maneuvers that can lead to prolonged fluoroscopy time and a higher rate of embolization. In our study, the presence of a Type 3 arch and angulated takeoff showed a trend towards increased time, but it was not statistically significant. It is possible that the limited power of our study due to the small number of patients may have failed to detect a small, but significant, difference between the two groups. Also consistent with prior literature, we have found that lesion-specific characteristics like ulceration or eccentricity do not appear to lead to prolonged fluoroscopy time.^3,21 Unlike previously-published reports, we also studied other anatomical details of aortic arch, including the distances of treated vessel from the uptake arch of the aorta, and found that the horizontal distance of the treated vessel from the origin of the arch was closely associated with prolonged fluoroscopic time, while the vertical distance of the treated artery from the base of the aortic arch was not associated with prolonged fluoroscopic time.
Increased fluoroscopic time reflects a technically challenging procedure and has been associated with increased neurological complications.⁹ Identifying the presence of aortic arch anomalies or high-risk anatomic characteristics before CAS is important for many reasons. It can give the operator a better idea of the procedural complexity involved so s/he can plan to modify the CAS technique and choose the most appropriate device.¹³ It can also guide the choice of interventionalists with an advanced skill set or referral of patients to centers with more experience in CAS. Since an aortic arch angiogram (or magnetic resonance/computerized tomographic angiography) can accurately reveal complex anatomic variations like vessel tortuosity, angulated takeoff and distance of the treated artery from the arch of the aorta, it may play an important role prior to CAS, especially for patients with advanced age, prior neck radiation, symptomatic disease or extensive comorbidities.²²
Study limitations. Several potential limitations concerning our study findings need to be addressed. First, many of our patients did not undergo arch angiography and were excluded from the study. Secondly, we excluded patients who developed complications during the intervention, some of which may have been due to complicated anatomy. While this was done to ensure that fluoroscopy time reflected procedural difficulty rather than intraprocedural delays due to other causes, this also precluded us from determining an accurate rate of procedural complications and adverse patient outcomes. This warrants the need for a future study that specifically looks at the effect of prolonged D1 and severe tortuosity on patient outcomes.

Conclusion
In conclusion, this study confirms prior observations that the anatomical characteristics of the aortic arch are important determinants of technical difficulty during CAS. More specifically, the distance from the origin of the treated artery to the beginning of the descending aorta and tortuosity predict prolonged CAS times. Future studies are required to evaluate these angiographic variables and to develop a scoring system to predict difficult CAS and its relationship to patient outcomes.

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