Carotid artery stenting prior to coronary artery bypass grafting in patients with carotid stenosis: Clinical outcomes

Abstract

Objectives

Management of patients undergoing coronary artery bypass grafting (CABG) with obstructive disease of the carotid arteries is still a matter of debate. We compared the results of staged carotid artery stenting (CAS) before CABG in patients with carotid lesions.

Materials and Method

Patients with significant carotid artery disease who were deemed to simultaneously suffer from an obstructive coronary artery disease requiring CABG from 2008 to 2018 were screened and enrolled in this study. We performed a staged CAS in cases with ≥60% stenosis and neurological symptoms or asymptomatic patients with ≥80% carotid artery stenosis. Patients with bilateral carotid lesions received sequential CAS within three weeks. Six weeks after the CAS procedure, all patients underwent CABG.

Results

A total of 142 patients were included. Eighty-five of these had neurological symptoms, while the remaining 40% were asymptomatic. Thirty-one patients underwent sequential CAS for bilateral lesions. The cerebrovascular event (CVE) following CAS (3 patients) and CABG (3 patients) was 4.2%. There was only a single case of mortality in this cohort. Although it was not statistically significant, CVE after CABG was more frequent in patients with bilateral carotid disease.

Conclusions

Our results showed that staged CAS could be performed with minimal adverse outcomes in patients suffering from a simultaneous occlusive disease of carotids and coronary arteries before CABG. Bilateral CAS will further decrease cerebrovascular events and could be performed consequently or concomitantly.

Introduction

Carotid artery stenosis accounts for 15% to 20% of patients with ischemic stroke or transient ischemic attack. The risk of a cerebrovascular event (CVE) after coronary artery bypass grafting (CABG) ranges between 2 to 4.8%.^1,2 This risk is increased among male patients and those who have diabetes, atrial fibrillation, patients with lesions of the left main coronary artery, and those with prior neurological symptoms related to the presence of occlusive carotid disease.^1,3

The incidence of CVE after CABG surgeries has been reported to increase among patients with concurrent severe carotid artery stenosis. In a systematic review, Das and colleagues reported an 11.5% higher risk of CVE after CABG revascularization if there was greater than 50% occlusion of the carotid arteries. ⁴ In another systematic review, Naylor et al. reported a 2.5% risk of stroke after CABG in patients with normal carotid arteries. ⁵ However, this risk doubled if the patients had asymptomatic stenosis of carotids and quadrupled if they had initial symptoms of carotid artery occlusion.

Several trials have demonstrated that the risk of postprocedural myocardial infarction (MI) following carotid endarterectomy (CEA) is twice as much as other types of surgery.^6,7 The common pathophysiology and coexistence of coronary artery disease (CAD) in patients with carotid occlusive disorders is the underlying reason for the higher incidence of myocardial injury following carotid procedure. According to the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), this risk does not decrease more in patients after carotid artery stenting (CAS) than CEA. ⁷ The risk of MI is even more enhanced in patients with significant CAD in whom urgent heart revascularization has been deemed necessary. The timing of CABG versus CEA/CAS is, therefore, a matter of controversy.^8–10

Therefore, staging CEA or CAS, followed by CABG, offers practical benefits by reducing stroke risk in these patients. For bilateral carotid lesions, a question arises whether both lesions should be stented simultaneously or follow each other. It is a common belief that simultaneous stenting of the contralateral carotid artery may increase periprocedural complications such as; hemodynamic impairment from stimulation of the carotid sinus baroreflex (severe bradycardia, hypotension) and the risk of cerebral hyperperfusion syndrome. ¹¹ Although there are reports of safe concomitant bilateral stenting of both carotid arteries,^12–14 we opted to stage CAS by a period of two weeks to avoid any potential side effects before CABG.

Herein, we describe a single-institute experience in staged CAS and CABG in its two major medical centers. We hypothesize that staged CAS reduces the post-CABG incidence of CVE to the levels comparable to CABG patients in the absence of significant carotid disease. We also hypothesize that most cerebral ischemic complications occur more often in patients who suffer from bilateral carotid stenosis.

Methods and patients

The Institutional Review Board approved this study under IR.MUQ.REC.1398.086. The study's experimental design was a retrospective review of a cohort of 4365 patients who underwent CABG from April 2008 and April 2018. All retrospective studies are generally exempted from obtaining individual informed consent from the participants. Indications for CABG surgery were based on the American College of Cardiology (ACC) / American Heart Association (AHA). Since our intervention center is the only regional referral center, only the patients deemed to benefit from CAS rather than CEA were referred to our center by the practicing cardiologists. Therefore, candidates in need of an urgent CABG (left primary coronary artery disease) were excluded.

Additionally, when a CEA was the preferred method of revascularization due to extensive calcified disease, type III aortic arch, or extreme angulations, the patients were directly referred to the vascular surgical services. Therefore, they were not included in this case series. As a part of the routine workup for CABG procedures, all participants completed a thorough neurological examination by an expert neurologist before the surgery and received a duplex ultrasound examination of their carotid arteries.

The flow diagram shows that 762 patients were over 60 years old or had a stroke or transient ischemic attack (TIA). As per routine, these patients were referred for magnetic resonance imaging (MRI) of the brain and duplex examination for screening occlusive diseases of the common or the internal carotid arteries (Figure 1). Following these initial screening studies, 430 patients were excluded for not having a significant occlusive disease of the carotid arteries, and 12 patients were excluded for having extensive brain injury secondary to prior CVE. The remaining 330 patients underwent head, and neck computerized tomographic angiography (CTA) since the patients’ initial screening with a duplex exam was generally performed by trainees with less clinical experience. One hundred fifty-four more patients were excluded for not having >60% internal/common carotid stenosis, and 33 patients were excluded for significant vertebrobasilar insufficiency. Five patients with intracranial aneurysms, plus one patient with arteriovenous malformation of the brain, were further excluded.

Fig. 1.

CONSORT flow diagram of the study.

All symptomatic patients with greater than 60% stenosis of the carotid arteries with a history of prior CVE and asymptomatic patients with stenosis of greater than 80% were scheduled for staged CAS before their scheduled CABG surgery. In the case of bilateral carotid artery stenosis, sequential CAS was performed within a three-week interval. Six weeks after the latest CAS procedure, all patients underwent CABG. Patients were evaluated early postoperative for neurologic deficit and possible intervention after CAS procedures, before the CABG procedure, and following the bypass surgery by an experienced neurologist in a regular interval up to twelve months for the postoperative occurrence of AMI, CVE, and death.

Eight days before the index CAS procedure, all patients received dual antiplatelet prophylaxis with oral administration of salicylic acid 81 mg and clopidogrel 75 mg every day and continued through the procedure. On the day of the CAS procedure, the patients received additional 5000 units of heparin. Dual antiplatelet treatment was continued for six weeks after the CAS procedure. Dual antiplatelet therapy was continued during the interval period of two consecutive CAS procedures for bilateral carotid lesions. Clopidogrel was continued after CAS until discontinuation seven days before CABG. The stenting procedure was performed using a fixed angiographic unit (Siemens AG, Munich, Germany) and a neuro-interventionist The angiography system was calibrated for consistency and accuracy of radiation parameters by the quality control kit. Appropriately sized, self-expanding stents without protection devices were deployed. ¹⁵ Following deployment of the stents and balloon dilatation, the cerebral vasculature patency was confirmed with digital subtraction angiography.

An integrated ionization chamber measured the patient exposure time and radiation dose (Diameter, PTW, Freiburg, Germany). They were reported as dose area product and fluoroscopy time following each procedure.

Statistical analysis and data management

All patients with an indication for staged CAS were included; therefore, we did not perform any power analysis and sample size determination. Relevant clinical, demographic, and radiation information were entered in a Microsoft Excel worksheet and transferred to SPSS program Version 25.0 (IBM Inc. Chicago, IL) for statistical analysis. Descriptive statistics were performed for all patients, and the results for categorical data were reported as the frequency with an appropriate percentage. The numerical variables were expressed as mean ± standard deviation if they were normally distributed. We further compared our findings to the available historical data and those with CABG procedures, which had no evidence of occlusive carotid diseases. We additionally compared outcome variables (the primary variable of CVE and secondary variables of death and post-procedural MI) between those with bilateral and those with unilateral carotid lesions. This comparison was performed by a non-parametric Mann Whitney U test for numerical variables and chi-square tests for categorical data. Null hypotheses were rejected at a 95% confidence interval with alpha values < 0.05.

Results

Eighty-five men and 58 women were enrolled in this study. Patients’ clinical and demographic information is tabulated in Table 1, according to the presence of unilateral or bilateral carotid diseases for comparison. The cohort's average age was 69.7 ± 4.9 years old, and the body mass index (BMI) was 28.6 ± 3.9 kg/m². Fifty-seven patients (39.9%) were asymptomatic, while the remaining 86 patients (60.1%) had a prior history of CVE in the form of TIA (35.7%) and/or stroke (22.4%) within 90 days of the time of enrollment. In all patients, CAS was technically successful.

Table 1.

Demographic and clinical characteristics of patients with unilateral and bilateral carotid diseases.

		Unilateral Stenting (N = 112)	Bilateral Stenting (N = 31)	P-Values
Gender	Female	46 (41.1)	12 (38.7)	0.840
	Male	66 (58.9)	19 (61.3)
Age (Years)		69.4 ± 4.8	71.0 ± 4.9	0.104
Body Mass Index (Kg/M^2)		28.7 ± 3.9	29.2 ± 3.1	0.512
Smoking within past 6 months		27 (24.1)	14 (45.2)	0.027
Hypertension		69 (61.6)	21 (67.7)	0.675
Dyslipidemia		23 (20.5)	6 (19.4)	>0.99
Diabetes mellitus		78 (69.6)	18 (58.1)	0.280
Presence of Symptoms		57 (50.9)	29 (93.5)	<0.001
Transient ischemic attacks (TIA)		31 (27.7)	20 (64.5)	<0.001
Amaurosis fugax		3 (2.7)	0 (0.0)	>0.99
Prior cerebrovascular accidents		23 (20.6)	9 (29.0)	0.335
Left ventricular ejection fraction (%)		30.1 ± 4.0	31.3 ± 4.3	0.148
Total number of coronary grafts		4 (3–4)	4 (3–4)	>0.99
Operative time (Hours)		5.7 ± 0.7	5.6 ± 0.7	0.482

Frequencies are shown as % (N) and numerical values are displayed as mean ± standard deviation. Asterisks indicated a significant difference between the group with a p value < 0.05.

All patients had triple-vessel coronary artery diseases. Thirty-one patients had bilateral carotid diseases and underwent sequential CAS before the CABG procedure, and the remaining 112 patients had unilateral carotid lesions requiring staged CAS. The left anterior descending artery (LAD) was the most common involved artery (90.2% of patients), followed by the right coronary artery (RCA) in 82.5% and the left circumflex artery (LCX) in 71.3% of the patients (Table 2). Sixty-six patients had lesions of the left carotid, and 46 patients presented with the right carotid disease. The patients’ cardiovascular profile was comparable in patients with unilateral and bilateral carotid diseases, and total operative times were similar between the two groups of patients (Table 1).

Table 2.

Radiation exposure and volume of contrast material use in patients with unilateral and bilateral carotid diseases.

	Unilateral Stenting (N = 112)	Bilateral Stenting (N = 31)	Overall (N = 143)
Dose area product μGy-m2	4557 ± 3765	5538 ± 1701	4769 ± 3443
Total fluoroscopy time (minutes)	3.9 ± 1.8	4.2 ± 1.2	3.9 ± 1.7
Contrast material volume (mL)	79.2 ± 25.6	111.9 ± 18.7*	86.3 ± 27.7

Numerical values are displayed as mean ± standard deviation for variables with normal distribution. Asterisks indicated a significant difference between the group with a p value < 0.050.

Radiation exposure was not any different among patients with unilateral and bilateral lesions of the carotids (Table 2). However, the volume of intravenous contrast was significantly smaller in patients during the CAS procedure of the unilateral lesions (79.2 ± 25.6 mL) compared to those with bilateral carotid diseases (111.9 ± 18.7 mL; P < 0.05).

As depicted in Table 3, the complications following staged CAS and CABG included 1 (0.7%) death, 2 (1.4%) MI, and 3 (2.1%) cases of CVE that occurred immediately after CABG. CVE, in the form of ischemic stroke, occurred exclusively in patients who had sequential CAS before their CABG surgery. Due to the smaller number of patients in each group, subgroup analysis failed to demonstrate a meaningful difference between unilateral versus bilateral staged CAS before CABG (Table 3). Moreover, there were no additional MI or CVE during the 12 months of the follow-up period.

Table 3.

Complications related to carotid artery stenting and coronary artery bypass grafting in patients with unilateral and bilateral carotid diseases.

	Unilateral Stenting (N = 112)	Bilateral Stenting (N = 31)	P-Values
Cerebrovascular event following carotid stenting	2 (1.8)	1 (3.2)	0.522
Cerebrovascular event following CABG	0 (0.0)	3 (9.7)	0.009
Myocardial reinfarction following CABG	2 (1.8)	0 (0.0)	>0.99
Surgical bleeding requiring exploration	2.7% (3)	2 (6.5)	0.296
Death	0 (0.0)	1 (3.2)	0.217
Other complication	1 (0.9)	0 (0.0)	>0.99

Frequencies are shown as N (%). Asterisks indicated a significant difference between the groups with a p value < 0.050.

Discussion

We found that a staged CAS was performed before CABG in 142 patients who suffered from a concomitant occlusive disease of the carotid artery and CAD needing revascularization. CAS was chosen over CEA as the method of cerebral revascularization. Both have comparable rates of post-procedural CVE with a lowered risk of cardiovascular complications such as acute postoperative MI. The lower risk of post-procedural MI following CAS than CEA has also been shown in patients with high-risk CAD. ¹⁶ Although most patients in this cohort had a prior history of neurological symptoms, a good percentage of asymptomatic patients underwent staged CAS purely based on angiographical findings.

The timing of carotid endarterectomy or percutaneous CAS in patients requiring CABG has been widely studied. Following the initial work by Illuminati and his coworkers, ¹⁷ it was routinely recommended to perform some forms of carotid revascularization (CEA or CAS) before CABG to reduce the risk of stroke. ¹⁸ Nevertheless, concomitant revascularization of coronary and carotid arteries is offered by several earlier generations of surgeons trained in Cardiovascular Surgery. By involving separate disciplines such as Cardiothoracic Surgery for CABG and Vascular/ Neurosurgery/ Interventional Radiology for carotid revascularization, it becomes a medicolegal issue as which service will take the credit for the adverse cerebrovascular event following CABG or AMI after the carotid intervention. The most common practice is to revascularize the organ with the most critical ischemia if staged revascularization is planned.

Moreover, sequential CAS was used to stage cerebral revascularization before CABG for bilateral carotid artery stenosis. Interestingly, all three patients (2.1%) who developed ischemic stroke following CABG had sequential CAS for bilateral carotid lesions. None of the patients who received staged CAS for unilateral lesions of the carotid developed CVE after CABG. The death rate was 0.7% after CABG in this cohort, comparable to the 1.2% mortality after CABG procedures performed in this center in patients without CAD. Due to the low number of patients in this cohort, the difference did not reach statistical significance (P = 0.187).

We understand that this study is underpowered to conclude the safety of bilateral CAS before CABG. A few studies have examined and shown that a concomitant CAS is as safe as staged CAS for bilateral carotid stenoses.^12–14 However, this study differed from the others in comparing the frequency of CVE following staged CAS for bilateral lesions versus CAS for unilateral carotid diseases before performing CABG. The results of this study were somewhat inconclusive. However, there was a trend of additive increase in the risk of CVE if the patients underwent bilateral CAS. These points were also discussed in the text of the manuscript.

CAS is recommended for cerebral revascularization of patients considered candidates for CABG due to the lower rate of post-procedural MI. The efficacy and risk-benefit ratio of CAS over CEA has been vastly studied for revascularization of carotid arteries. In a systematic review, Naylor et al. evaluated 22 studies that reported 760 staged CAS procedures followed by CABG and 7753 CEA surgeries and CABG performed simultaneously. ¹⁹ Comparable to our study, the stroke rate in the CAS group was 3.3%, and the risk of 30-day MI was 1.8%, with an overall mortality rate of 5.5%. While the chances of death (4.6%) and ischemic stroke (4.5%) were similar, the risk of MI was nearly two times (3.6%) following simultaneous CEA and CABG compared to the staged CAS-CABG group.

Similarly, Shishebor et al. studied 110 patients managed with staged CAS and 195 with concurrent CEA and CABG. ²⁰ These investigators reported 3% MI, 2% stroke, and 6% mortality rate in the CAS group compared to 5% MI, 7% stroke, and 5% death rate in the CEA group. The rates of complications in our study were comparable with the results of other studies. Ziada et al. also reported a 3% rate of MI and a 2% rate of CVE following CABG in patients treated with staged CAS. ²¹ In a study by Okomato et al., 20 patients with severe carotid diseases received prophylactic CAS before CABG, and five patients were treated with CAS after they had CABG. They also aggressively treated four patients with high coronary artery lesions by anastomosing the superficial temporal artery to the middle cerebral artery. Patients in this study had a relatively higher risk (5%) of ischemic stroke by comparison; smaller sample size and the complicated anatomy of these patients were the main limiting features of this study that distanced its results from the mainstream. ²² In a relatively more extensive study, staged CAS before CABG was performed in 356 asymptomatic patients. These investigators reported a 6.7% overall rate of MI, death, or stroke composite complication from the time of CAS until 30 days following CABG. ²³ The frequency rates for individual complications in this study were comparable to those observed in our cohort.

A few other smaller size studies that examined the clinical outcome after staged CAS and CABG reported no adverse events (death, MI, stroke) within 30 days and only one case of ischemic stroke in a 2-year follow up period.^24,25 In another study, six patients developed a composite complication (death, MI or stroke) after staged CAS in 62 patients. ²⁶ Four of these patients (6.4%) suffered from a stroke, 2 (3.2%) from MI, and 3 (4.8%) patients died after CABG related to CVE complications. The incidence of CVE was 7.6% in 277 patients after sequential staged CAS for bilateral carotid lesions before CABG. The majority of these patients demonstrated stroke symptoms after the CAS procedures, and only 6 (2.2%) patients had CVE after the CABG procedure. ²⁷ The clinical outcome was, for the most part, the clinical work was better or on par with the results of other studies that utilized this protocol.

Moreover, 31 patients in this cohort had severe bilateral carotid stenosis, which needed sequential CAS. It is essential to add that with the patients in this cohort. The radiation exposure rate was comparable to that registered for all patients during complex lesion angioplasty used for similar indications.^28,29

This study was limited by its non-randomized nature and lack of a control group. Optimally designed research would include a group of patients with significant disease of the carotid arteries. The CABG procedure would randomly proceed without any intervention on their carotids. Nonetheless, this type of practice is neither ethical nor practical on these critically ill patients, which would intentionally increase the risk of CVE. Some may also perceive that the lack of using a protection device during the application of the self-expanding stents is not a common practice. However, as McDonald et al. also demonstrated, ³⁰ it has been our experience that not using a protection device before applying the stent is non-inferior, or it may be advantageous over the use of protection devices, which may increase the injury the carotid arteries. ¹⁵ Additional protection devices would be another limiting factor in developing countries where the patients or a third-party payer may not afford its financial impact.

Conclusion

We conclude that staging patients with CAS before CABG operation improves patients’ clinical outcomes suffering from concomitant CAD and carotid occlusive disease as the death rate after CABG in these patients is comparable to that in patients undergoing CABG without the carotid occlusive disease. The risk of CVE, particularly an ischemic stroke of the ipsilateral cerebral hemisphere, is relatively minimal, making staged CAS the therapeutic standard before CABG for these patients. Considering the findings provided in this study and those previously published, the staged protocol will only be improved with advances in stenting technology and brain protection during the stent-grafts application.