Management of Severe Bilateral Carotid Artery Stenosis Concomitant to Severely Symptomatic CAD Requiring CABG (Full Title Below)

Management of Severe Bilateral Carotid Artery Stenosis Concomitant to Severely Symptomatic Coronary Arterial Disease Requiring Coronary Artery Bypass Grafting: A Case-Based Review

ABSTRACT: Patients with significant carotid disease have an increased risk of stroke during coronary artery bypass grafting (CABG). However, due to its inherent risk and to the variety of mechanisms responsible for postoperative stroke, prophylactic carotid endarterectomy has an uncertain value, particularly in cases of asymptomatic unilateral carotid disease. In addition, the timing and sequence of coronary and carotid surgeries are controversial matters. Prophylactic carotid artery stenting is emerging as a potentially safer strategy. The major limitation of carotid stenting is the need for one month of dual antiplatelet therapy and the potential need to postpone CABG, which is not possible in patients with refractory unstable coronary syndromes. We describe the case of a patient with severe unstable coronary artery disease and bilateral carotid artery disease who was successfully managed with stenting of the most critical coronary lesion, staged bilateral carotid stenting, followed by CABG three weeks later. J INVASIVE CARDIOL 2010;22:E192–E196 ———————————————————————— In patients who require coronary artery bypass grafting (CABG), the risk of perioperative stroke is close to 2%.¹ Several observational studies have consistently reported that the risk of stroke associated with CABG is 2–4 These figures, however, increase to 5% in those with bilateral carotid stenosis or a history of stroke or transient ischemic attack (TIA) and to 7% to 11% in patients with carotid occlusion.^2–4 Since ~6% of patients undergoing CABG have significant carotid disease, combined carotid and cardiac surgical procedures are performed frequently in an effort to reduce the incidence of postoperative stroke.⁵ The timing and sequence of revascularization are controversial and influenced by the respective symptom severity of the coronary and carotid disease. Recent evidence suggests that carotid stenting can be safely performed before CABG, offering an alternative to carotid endarterectomy for patients with severe coronary arterial disease (CAD). We describe the management of a challenging case of severe carotid and coronary disease.
Case report. The patient is a 60-year old man with a history of Type 2 diabetes mellitus, hypertension, chronic kidney disease (creatinine clearance 50 ml/min/m²), and a history of left-sided transient ischemic attack (TIA) 5 months prior to his presentation. He was diagnosed with severe bilateral carotid artery stenosis on a carotid duplex and was being considered for bilateral carotid endarterectomy (CEA). Meanwhile, the patient presented with severe angina on minimal exertion that warranted hospitalization. His cardiac biomarkers remained negative, but despite aggressive anti-anginal therapy, he was having recurrent angina at rest and at minimal activity with marked ST depression. Coronary angiography was performed and revealed a left dominant system, significant left main disease and three-vessel disease: 50% distal left main stenosis, serial 70% and 95% mid-left anterior descending artery (LAD) stenosis, 60% proximal and distal left circumflex stenosis, and 75% stenosis of the first obtuse marginal branch (Figures 1 and 2). The patient’s coronary SYNTAX score, an angiograhic tool that grades the extent and complexity of coronary arterial disease, was 42. We performed bilateral carotid angiography which revealed a 60% ulcerated right internal carotid artery stenosis (symptomatic side) and a 90% left internal carotid artery stenosis (Figures 3 and 4).

Discussion

Management options. Which one of the following is the best management option for this patient with extensive severely symptomatic coronary arterial disease and bilateral symptomatic carotid artery disease?

1. CABG followed by elective CEA (=staged CABG-CEA, CABG being performed first because of the severity and instability of his coronary syndrome). 2. Combined (synchronous) CABG and bilateral CEA. 3. Staged bilateral carotid artery stenting, followed by CABG five weeks after the last carotid procedure, in order to allow for 4 weeks of dual antiplatelet therapy and 5–7 days of clopidogrel cessation before CABG. 4. Staged bilateral carotid artery stenting followed by CABG a few days later, while the patient is still receiving dual antiplatelet therapy. 5. Complete percutaneous coronary revascularization followed by elective carotid revascularization.

Discussion of the validity of these management options. Optimal management of patients with severe coronary and carotid stenosis is not defined. Randomized controlled trials of prophylactic revascularization synchronous to CABG or preceding CABG are lacking. Many experts argue that there is limited evidence to support the contention that carotid revascularization prevents post-operative stroke, and any conferred benefit by prophylactic CEA may be offset by the relatively high procedural risk.^6–8 In fact, systematic reviews and registry analyses failed to show any benefit of prophylactic CEA, particularly CEA performed concomitantly to CABG, despite risk-adjustment or risk-matching.^3,9,10–12 In another recent analysis, preoperative CEA did not reduce the incidence of stroke, and most strokes occurred in patients without any carotid disease (76%) or in patients with carotid disease receiving synchronous CABG-CEA.⁵ In addition, Naylor et al noted in an extensive review that primary carotid disease alone is responsible for less than 40% of post-operative strokes, the rest being due to aortic atheroembolization, post-operative hypercoagulable state and atrial fibrillation;³ sixty percent of strokes on CT scanning have a distribution that is not confined to a single carotid artery. This partly explains the limited benefit of prophylactic carotid revascularization. Thus, there seems to be little evidence to justify prophylactic CEA in CABG patients with severe unilateral asymptomatic carotid disease. However, since the available data are retrospective and unable to account for unmeasured confounding variables, there is an agreement that prophylactic carotid intervention is still justified in CABG patients with carotid stenosis > 50% and a prior history of stroke or TIA, and probably in patients with asymptomatic severe (greater than or equal to 80%) bilateral carotid stenosis.^2,7 Of importance, the registry analyses mentioned previously did not particularly study cases of severe bilateral carotid disease and/or bilateral CEA. Thus, proceeding with CABG without performing any prophylactic carotid intervention in our patient with a history of TIA and severe bilateral carotid disease is believed to be associated with a high stroke risk. When CEA is performed along with CABG, the timing and sequence of revascularization are controversial and influenced by the respective symptom severity of the coronary and carotid disease. The consensus document of the American College of Cardiology (ACC) states that CABG alone is reasonable for patients with asymptomatic carotid stenosis and critical left main disease, refractory acute coronary syndromes, or other indications for urgent CABG. In contrast, patients with recent (less than 2 weeks) TIA and carotid stenosis greater than 50% should be considered for urgent CEA, if CABG can be safely deferred for several days.² The management of a patient with severe and symptomatic carotid and coronary disease and the role of synchronous CABG-CEA are unclear. A systematic review of 97 published studies following 8972 staged or synchronous CABG–CEA operations has shown a 10–12% incidence of death or major cardiovascular morbidity (stroke, myocardial infarction [MI]) within 30 days of surgery in patients undergoing staged or synchronous procedures.⁴ Overall, there was no significant difference in the combined outcomes for staged and synchronous procedures, but death was highest for the synchronous CEA-CABG, stroke was highest for staged CABG first-CEA second, and MI was highest for staged CEA first-CABG second. A recent registry suggested that the risk of stroke is higher in patients undergoing synchronous CABG-CEA as opposed to staged CEA first-CABG second or staged carotid stenting-CABG.⁵ As noted previously, synchronous CEA-CABG failed to show any benefit in comparison to CABG alone in registry analyses. The longer operative time and general anesthesia duration in the synchronous CEA-CABG cases are probably the most significant contributors to the stroke and mortality risk. It is also possible that the profound hypotension that frequently follows carotid revascularization as a result of carotid sinus baroreceptor manipulation results in severe diminution of coronary perfusion, especially with the underlying severe coronary disease. Moreover, early postoperative use of additional or larger doses of pressors to treat hypotension after CEA in general and after CEA + CABG in particular may be deleterious in patients with CAD.^13,14 On the other hand, the hemodynamic stress of cardiopulmonary bypass may be deleterious immediately after CEA.¹⁵ Thus, concomitant bilateral CEA-CABG seems a suboptimal approach to managing our patient. This controversy over the timing and value of prophylactic CEA created enthusiasm for carotid stenting before CABG. Ziada et al retrospectively analyzed outcomes of patients managed with carotid artery stenting (CAS) followed by CABG at a median of 39 days later. Despite a higher baseline risk profile, CAS was associated with a 4 times lower rate of MI and stroke in comparison to the combination of CEA and CABG.¹⁵ This low event rate was duplicated in other retrospective analyses. Van der Hayden et al assessed the safety and feasibility of unilateral or staged bilateral CAS, followed by CABG, in patients with asymptomatic uni- or bilateral carotid artery stenosis. They not only found low periprocedural morbidity and mortality of 4.8% for death and stroke at 30 days but also durable long-term results (71.4% freedom from all stroke and death at 5 years).¹⁶ Another large retrospective study looked at the outcomes of patients who underwent CAS-CABG and CEA-CABG within the same hospitalization, without specifying how many underwent synchronous CEA-CABG. This study showed the efficacy of staged CAS and CABG in terms of perioperative complications among patients with asymptomatic carotid artery stenosis and suggested that this approach may be a valuable, if not preferable, alternative to CEA-CABG.¹⁷ This potential advantage of CAS over CEA in patients with severe CAD requiring CABG may be explained by the less invasive nature of CAS. Although potential adverse hemodynamic depression may occur with CAS, it is generally easier to manage than the hypotension occurring after CEA, with less requirement for vasopressors.¹⁵ However, the need for dual antiplatelet therapy precludes immediate CABG and seems to limit the utility of CAS in patients with refractory unstable coronary artery disease. Currently, the American College of Cardiology guidelines recommend clopidogrel therapy for at least one month after carotid stenting.² This brings a critical question: is it necessary to postpone CABG in order to allow for 4 weeks of dual antiplatelet therapy? Withholding clopidogrel soon after CAS and performing earlier CABG may prove unsafe and increase the risk of stent thrombosis as suggested in a retrospective study,¹⁷ and dramatically increase the risk of early neurological complications as shown in a small randomized trial.¹⁸ Performing CABG under dual antiplatelet therapy, on the other hand, increases major bleeding risk as suggested in the CURE trial (6.3% vs. 9.6%, p=0.06).¹⁹ Although dual antiplatelet therapy did not increase the mortality of patients undergoing CABG, the absolute bleeding risk was increased by up to 9% in some registries, with an absolute increase in the risk of reoperation for bleeding of 1.5–4%.20 To overcome this issue, one option may be to reduce the duration of dual anti-platelet therapy to 2 weeks after carotid stenting. In fact, clopidogrel therapy for 2 weeks only after carotid stenting may be acceptable, allowing earlier performance of CABG. In the trial that established the safety and efficacy of CAS in comparison to CEA (SAPPHIRE trial), clopidogrel therapy was recommended and used for 2 to 4 weeks after stenting.²¹ A second option is to perform CABG under dual antiplatelet therapy, taking into account the potential bleeding risk. Ranaweera et al reported a small series of 20 patients with unilateral carotid stenosis who underwent carotid stenting followed by CABG during the same hospital admission. CABG was performed under dual antiplatelet therapy at a mean of 6.4 days after CAS. No strokes or deaths occurred at a mean follow-up of 486 days, and transfusion rates were not excessive.²² A recent small trial of 37 patients suggested that in elevated surgical risk patients with carotid disease, hybrid revascularization by CAS, followed immediately by CABG, is a feasible, safe and promising therapeutic strategy, with 2 major post-operative bleeding events and one stroke event;²³ CAS was performed under aspirin and heparin therapy, while clopidogrel load was started 6 hours after CABG. In our patient with high perioperative stroke risk, we considered the alternative option of complete multivessel percutaneous coronary revascularization, which is associated with a four times lower rate of cerebrovascular events than CABG.¹ In patients with left main and/or 3-vessel CAD randomized to the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) trial, percutaneous coronary intervention (PCI) was clearly inferior to CABG in reducing the combined endpoint of major adverse cardiovascular and cerebrovascular events in patients with high SYNTAX scores greater than or equal to 33 (event rate at one year 15.4% vs. 28.2%, p 1 Thus, complete percutaneous coronary revascularization is a suboptimal therapeutic strategy for our patient. Our management strategy. We decided to pursue the strategy of staged bilateral carotid artery stenting followed by CABG five weeks after the last carotid procedure, i.e., after finishing a 4-week course of clopidogrel therapy. Meanwhile, due to the severity of our patient’s angina, and in order to stabilize his acute coronary syndrome and reduce his risk of myocardial infarction and recurrent ischemia over the next 5–6 weeks^24,25 we decided to treat the most severe lesion (mid-LAD) with balloon angioplasty or bare-metal stent. If severe ischemia was to persist, the patient would undergo CABG under dual antiplatelet therapy. We treated the mid-LAD stenosis with a bare-metal stent (Figure 5). The more proximal 70% stenosis at a bifurcation with a large diagonal branch was left untreated. The patient’s angina significantly improved and he was able to perform moderate activity without any angina. Twenty-four hours post-PCI, we performed left internal carotid artery stenting, and 2 weeks later, we performed right internal carotid artery stenting without any complication. Three weeks after the last carotid revascularization, the patient developed angina on heavy exertion without any rise in cardiac biomarkers, yet the severity of his angina triggered hospital admission. We then decided to refer him for CABG earlier than initially planned. Clopidogrel was stopped and 3-vessel CABG performed 3 days after clopidogrel cessation. He had an uneventful post-operative course without any stroke or myocardial infarction. Three months later, he is free of angina and of any cardiovascular events. Conclusion. This case illustrates the complexity of management of concomitant coronary and carotid disease. In the absence of randomized trials comparing CAS before CABG, CEA before CABG, CEA synchronous to CABG, and no revascularization before CABG, management needs to be individualized using the generally agreed upon concepts. Staged bilateral carotid stenting and culprit coronary artery stenting followed by complete coronary revascularization with CABG several weeks later proved successful in the management of our patient.

References

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—————————————————————— From the Department of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. The authors report no conflicts of interest regarding the content herein. Manuscript submitted February 11, 2010 and accepted February 22, 2010. Address for correspondence: Elias B. Hanna, MD, Department of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, 920 S.L. Young Boulevard, WP# 3010, Oklahoma City, OK 73104. Email: elias-hanna@ouhsc.edu or ehanna10@yahoo.com