Chapter 23. Myocardial Revascularization with Carotid Artery Disease

Next to operative mortality, permanent stroke is the most dreaded complication of myocardial revascularization, not only because of the potential devastating consequences to the patient but also because of the increased cost of hospitalization and posthospital care. Perioperative stroke following coronary artery bypass grafting (CABG) is of increasing concern because as the average age of coronary bypass patients rises, so does the risk of stroke. This chapter investigates the relationship of carotid artery disease to neurologic complications following myocardial revascularization and evaluates treatment options for dealing with severe concomitant carotid and coronary artery disease (CAD).

Incidence of Perioperative Stroke

The risk of stroke coincident with CABG is well defined. In 1986, Gardner and colleagues1 found the risk of stroke to be a direct function of patient age. Patients younger than 45 years of age had a stroke rate of 0.2%, which rose to 3.0% for patients in their 60s and to 8.0% for patients older than age 75. Other risk factors associated with stroke were preexisting cerebrovascular disease, ascending aortic atherosclerosis, long cardiopulmonary bypass time, and perioperative hypotension.

Tuman and colleagues2 in 1992 investigated the effect of age on cardiac performance and neurologic injury in coronary bypass patients. Whereas the rates of low cardiac output and myocardial infarction (MI) were constant as patient age increased, the incidence of neurologic damage rose exponentially after age 65. The stroke rate rose from 0.9% for patients younger than 65 years to 8.9% for patients older than age 75.

To place the problem of the increasing patient age into a more contemporary context, at our institution the mean age of coronary artery bypass (CABG) patients rose from 56 years in 1980 to older than 67 years in 2007. In 1980 only 6% of patients were age 70 or older, whereas by 2007 more than 41% were age 70 or older, and 10% were age 80 or older.

In 2000, John and colleagues3 reported a stroke rate of 1.4% for 19,224 coronary bypass patients from the New York State Cardiac Surgical Database. Multivariable predictors of stroke included aortic calcification, renal failure, prior stroke, smoking, carotid artery disease, age, peripheral vascular disease, and diabetes. In their review of 10,860 patients having primary myocardial revascularization, Puskas and colleagues noted that stroke occurred in 2.2%.4 Multivariable predictors of stroke were age, previous transient ischemic attack, and carotid bruits.

Cost of Perioperative Stroke

Puskas and colleagues also found that perioperative stroke was associated with significantly more in-hospital morbidity, longer length of stay, and almost twice the hospital cost.4 Patients who suffered a perioperative stroke had a 23% hospital mortality rate. Roach and colleagues5 noted a 21% mortality rate for patients suffering a perioperative stroke following coronary artery bypass grafting (CABG), with a mean hospital stay of 25 days among survivors.

Causes of Perioperative Stroke

Possible causes of perioperative neurologic injury are listed in Table 23-1. The most common cause of perioperative stroke is atherosclerotic or thrombotic emboli from the heart or major vessels. Intracardiac emboli can arise from mural thrombus secondary to MI, left atrial thrombus associated with valvular disease or atrial fibrillation, or suture lines in the aorta or left side of the heart. Catheters in the left side of the heart also can be a source of perioperative emboli. Less commonly, entrapped air may cause neurologic events, although rarely focal deficits.

The aorta is also a possible source of emboli. Cannulation of the ascending aorta for bypass, aortic occlusion clamps, and intra-aortic cardioplegia delivery devices may dislodge existing atherosclerotic material from the aorta. Wareing and colleagues6 found aortic atherosclerosis to be a risk factor for perioperative stroke. Intraoperative echocardiography of the ascending aorta to identify atherosclerosis and the subsequent alteration of operative techniques to address identified problems improved the stroke risk in their patients. Studies that examine the anatomic distribution of perioperative strokes emphasize the importance of cardiac and aortic sources because diffuse anterior and posterior cerebral circulation beds are often affected.7,8

Embolism from atherosclerotic carotid bifurcation disease is a well-defined cause of perioperative neurologic injury. Carotid plaque morphology has an important impact on the stroke risk of patients with carotid stenosis. A companion study to the North American Symptomatic Carotid Endarterectomy Trial found that plaque ulceration was a significant incremental risk factor for stroke across all degrees of carotid stenosis.9

Many studies list flow-limiting carotid stenosis as a risk factor for perioperative stroke, but whether the carotid lesion is an etiologic factor or only a nonspecific marker of overall risk is unclear.1,10–12 The Buffalo Cardiac Cerebral Study Group found that although carotid stenosis predicted increased risk of perioperative stroke and death, most strokes occurred more than 24 hours after the myocardial revascularization, and the anatomic distribution of the strokes did not correlate well with the site of the carotid lesion.12,13

Neurologic injury can result from inadequate blood flow on cardiopulmonary bypass. Schwartz and colleagues, found that cerebral blood flow depends on arterial perfusion pressures, not on cardiopulmonary bypass flow rates.14 Low cerebral blood flow occurred with perfusion pressures of less than 60 mm Hg and was not influenced by the pump flow rate. Adequate perfusion pressure is very important in the presence of carotid stenosis, particularly with internal carotid occlusion.10 Some investigators have shown a linear relationship between the degree of carotid stenosis and the risk of perioperative stroke; in such analyses patients with total ICA occlusion are typically the subgroup at highest risk for stroke.7 Yet carotid revascularization is not possible in the circumstance of total ICA occlusion. When there is occlusion of carotid or intracerebral arteries, brain blood flow depends on collateral circulation, which, in turn, depends on perfusion pressure. Whether carotid or intracerebral vascular spasm can contribute to neurologic injury is unknown.

Finally, intracranial hemorrhage can lead to neurologic injury following cardiopulmonary bypass, but this is truly rare, despite the fact that patients are fully anticoagulated for cardiopulmonary bypass. We routinely use computed tomographic (CT) scanning to evaluate suspected perioperative stroke to guide anticoagulation, and the finding of primary intracerebral bleeding is extraordinarily uncommon. Indeed in a study of nearly 400 strokes after CABG, investigators of the Northern New England Cardiovascular Study Group identified hemorrhage as the cause of 1% of post-CABG strokes, and hypoperfusion as being responsible in about 10%.8

Of the potential causes of perioperative neurologic injury listed in Table 23-1, carotid stenosis is the one situation for which the surgeon can take action to remove the pathology. Because carotid stenosis is a significant risk factor for perioperative stroke, the need to define carotid disease before coronary artery grafting becomes obvious. The logical extension that surgical correction of carotid stenosis can decrease the risk of stroke has been the basis of our approach for many years. Although Level I evidence to support this approach does not exist, the safety of the combined operative approach, which is key to its continued application, has been verified, as will be discussed.

Relationship of Carotid Stenosis to Perioperative Stroke

Early studies relating the presence of carotid stenosis to perioperative stroke used auscultatory evidence of carotid disease as a surrogate for carotid stenosis. In 1988, Reed and colleagues from our institution documented a 3.9-fold increase in the risk for stroke after coronary artery bypass grafting in the presence of a preoperative carotid bruit.15

Yet carotid bruits are not reliable indicators of either the presence or degree of carotid stenosis. Sauve and colleagues16 found poor correlation between carotid bruits and the degree of stenosis. Indeed, as carotid lesions progress to high degrees of stenosis, bruits may become inaudible. Despite these limitations, auscultation for carotid bruits is a common mode of detecting carotid stenosis, particularly in asymptomatic patients.

Currently, Doppler ultrasound–based noninvasive studies are the initially applied and often definitive (and sufficient) diagnostic testing modality for carotid stenosis. Although quality control is essential with noninvasive testing, verification of its accuracy has been demonstrated many times.17,18

Brener and colleagues10 studied 4047 cardiac surgical patients and found a 9.2% rate of stroke or transient ischemic attack in patients with asymptomatic carotid stenosis, significantly greater than the 1.3% rate in patients with no carotid stenosis.

Faggioli and colleagues19 in 1990 reported that routine carotid noninvasive testing in CABG patients with no ischemic neurologic symptoms yielded an odds ratio for stroke of 9.9 with greater than 75% carotid stenosis. In patients older than age 60 with greater than 75% carotid stenosis, the stroke rate was 15 versus 0.6% for patients of the same age with no carotid disease. Perioperative strokes occurred in 4 (14.3%) of 28 patients who had greater than 75% carotid stenosis who did not have concomitant carotid endarterectomy compared with no strokes in the 19 patients with greater than 75% carotid stenosis who had a prophylactic carotid endarterectomy with their CABG.

In 1992, Berens and colleagues,20 using routine carotid duplex scanning for cardiac surgical patients 65 years of age or older, found that the risk of stroke was 2.5% for carotid stenoses greater than 50%, 7.6% for carotid stenoses greater than 50%, 10.9% for carotid stenoses greater than 80%, and 10.9% for unilateral carotid artery occlusion.

Thus, adequate evidence exists that significant carotid artery stenosis is an important incremental risk factor for the development of perioperative neurologic injury following CABG. In addition, the study by Faggioli and colleagues19 suggested that carotid endarterectomy performed with CABG yielded a lower stroke rate.

Mechanism of Perioperative Stroke with Carotid Stenosis

How carotid stenoses cause perioperative strokes is not well understood, especially because patients are fully anticoagulated on cardiopulmonary bypass. Perioperative strokes may result from emboli from the carotid plaque, possibly caused by dynamic plaque events. Loss of pulsatile perfusion or inadequate perfusion pressure on bypass may lead to diminished flow distal to a significant stenosis, resulting in a watershed stroke. Indeed the belief that hypoperfusion is a mechanism whereby carotid lesions cause stroke is indirectly supported by several observations, including the high stroke risk in patients with total ICA occlusion. Hypoperfusion was identified as causing about 10% of strokes in one review of post-CABG stroke pathology.8 However, Reed and colleagues15 and Ricotta 12 found that more than one-half of strokes present after the immediate postoperative period. Such delayed strokes in patients with uncorrected carotid stenoses may be related to the prothrombotic milieu that occurs in the early days after cardiopulmonary bypass, potentially causing destabilization of a previously asymptomatic carotid lesion.

Relationship of Uncorrected Carotid Stenosis to Late Stroke

In 1985, Barnes 21 assessed the late risk of untreated asymptomatic carotid stenosis in 65 patients who had cardiovascular operations, of whom 40 had CABG. At mean follow-up of only 22 months, 10% of coronary bypass patients had died, and 17.5% had suffered a stroke. Noninvasive testing revealed progression of the carotid disease in one-half of the patients within 4 years. Ascher reported a 10% risk of stroke after CABG at a mean follow-up interval of 48 months when significant carotid disease was uncorrected, 10-fold higher than patients undergoing combined CABG and carotid endarterectomy.22 Contemporary randomized trials of surgery versus medical therapy for significant carotid stenosis have defined the late risk of carotid-related stroke in medically treated patients. In the Asymptomatic Carotid Surgery Trial, actuarial risk of stroke at 5 years was 12% in medically treated patients with asymptomatic high-grade carotid stenosis.23

Incidence of Carotid Stenosis in Coronary Artery Bypass Patients

In 1977, Mehigan and colleagues,24 used noninvasive testing in 874 patients before coronary grafting and found a 6% incidence of significant extracranial cerebrovascular disease. Ivey and colleagues25 reported that routine ultrasonic duplex scanning for a history of neurologic events or cervical bruits in 1035 patients having isolated CABG revealed significant carotid artery stenosis in 86 patients (8.3%). Faggioli evaluated 539 neurologically asymptomatic CABG patients and found 8.7% had a carotid stenosis greater than 75%.19 The rate rose from 3.8% for patients less than age 60 to 11.3% for patients older than age 60. Berens and colleagues, using routine carotid artery scanning in 1087 cardiac surgery candidates 65 years of age or older (91% with coronary disease), found 186 (17.0%) had a greater than 50% carotid stenosis and 65 (5.9%) had a greater than 80% carotid stenosis.20 Predictors of carotid artery disease were female gender, peripheral vascular disease, history of transient ischemic attacks (TIAs) or stroke, smoking history, and left main CAD. D'Agostino, using noninvasive testing in 1279 CABG candidates, found 262 (20.5%) had greater than 50% stenosis in at least one carotid artery and 23 (1.8%) had bilateral stenoses greater than 80%.26 Significant multivariable predictors of carotid disease were age, diabetes, female sex, left main CAD, prior stroke, peripheral vascular disease, and smoking.

Virtually all studies have emphasized that patient age is the single highest risk variable. One report demonstrated a dramatic, statistically significant increase in patients older than 60 years of age. Diabetes, smoking, and hypertension were important associated risk factors, such that, with all three risk factors in patients older than age 60, the incidence of significant carotid stenosis nearly doubled from about 8% to 14%.22

Diagnosis of Carotid Artery Disease

Essentials of Noninvasive Testing

Ultrasound-based Doppler interrogation for carotid stenosis exploits the Doppler effect; namely, the reflected or altered frequency of an ultrasound wave is shifted in proportion to the velocities of the sampled, flowing blood, which are increased in regions of significant arterial stenosis.

Doppler interrogation produces two data sets—Doppler-shifted flow velocities in regions of interest, and spectral analysis of turbulent flow, which lends a qualitative determination of stenosis severity. Doppler samples must be obtained in the tightest portion of the stenosis for accuracy.

Derived Doppler velocities include peak systolic velocity (PSV), end-diastolic velocity (EDV), and the ratio between the PSV in the internal carotid artery and in the proximal common carotid artery (ICA/CCA ratio). The derived ratio corrects for baseline variations in hemodynamics, such as cardiac output and increased overall flows that might be noted in contralateral internal carotid occlusion. PSV is the single most important criterion, followed by the ICA/CCA ratio. EDV is helpful in discriminating severe versus “very severe” lesions. An ICA/CCA ratio of more than 4.0 equates to a greater than 70% diameter stenosis, the general threshold for a flow-reducing lesion at basal conditions according to the physics of critical arterial stenosis.

Some general comments about the efficacy of ultrasound-based carotid noninvasive tests are in order because many vascular surgeons proceed to carotid endarterectomy based solely on these preoperative studies.15 Surgeons must be familiar with the specifics of noninvasive diagnostic criteria, and laboratories must have quality-control documentation of accuracy. Thorough knowledge of the translation of ultrasound-derived data to corresponding degrees of internal carotid artery stenosis is necessary.

Indications for Noninvasive Testing

Current indications for screening patients for carotid artery disease before surgical myocardial revascularization include:

1. An audible bruit in the neck

2. History of a prior stroke

3. History of transient ischemic attacks

4. Patients with severe peripheral vascular disease

5. Patients with a prior carotid endarterectomy

6. Elderly patients

All of these indications are self-explanatory except the last. Because the incidence of carotid stenosis rises dramatically in patients older than age 65, there must be an age above which it is cost-effective to screen all patients for carotid disease. However, that age has not yet been determined. One would have to demonstrate the cost advantage of routine carotid endarterectomy versus that of strokes related to uncorrected carotid stenoses.

Role of Carotid Imaging Modalities

Catheter-Based Carotid Angiography

Although catheter-based carotid angiography yields excellent detailed images of the carotid and intracranial vessels, angiography is expensive, requires potentially nephrotoxic contrast material, and is not without risks, including arterial dissection and stroke. Cholesterol embolization owing to catheter manipulation in a diseased aorta can cause emboli to other vascular distributions, especially renal and/or other visceral arteries. (Indeed, in the Asymptomatic Carotid Atherosclerosis Study, one-half of the 2.3% stroke risk with carotid endarterectomy was referable to mandated angiography.27) For these reasons, conventional carotid angiography had all but vanished from the practice of many vascular surgeons by the year 2000.28 Ironically, current enthusiasm for carotid stenting has resurrected carotid angiography as a diagnostic and therapeutic tool.

Magnetic Resonance Angiography

Great enthusiasm in the 1990s arose for magnetic resonance angiography (MRA) to better define carotid lesions. Compared with catheter-based angiography, it was noninvasive, lacked nephrotoxicity, and when used with diffusion-weighted brain imaging, yielded an accurate map of the intracranial circulation. However, its limitations soon became obvious. Magnetic resonance vascular imaging relies on reflected magnetic pulses of flowing blood cells that vary as a function of flow turbulence. Because turbulent flow is characteristic of high-grade carotid stenoses, signal “dropout” in magnetic resonance imaging (MRI) is common. MRA suffers from low specificity with respect to detection of critical stenosis.29 Indeed, MRA alone can overestimate carotid stenosis severity. Thus, in a reversal of prior algorithms, we insist that stenosis severity information from MRA be verified by a duplex study.

Computed Tomographic Angiography

Computed tomographic angiography (CTA) is the noninvasive test of choice when supplemental information is required after duplex scanning. Although CTA requires iodinated contrast material, it can provide excellent arterial mapping from the aortic arch to the intracranial vasculature, which can be important to both vascular and cardiac surgeons. Accurate assessment of residual lumen diameter within a carotid artery lesion is obtained from both axial and three-dimensional (3D) reconstructed images. Current processing capabilities and the generation of 3D models have improved CTA accuracy in highly calcified lesions.

C. Miller Fisher's original description of the relationship of ipsilateral hemispheric stroke to internal carotid artery occlusion in 195130 was followed by Eastcott's description of surgical therapy for symptomatic carotid artery atherosclerosis in 1953.31 Thereafter, carotid endarterectomy became popular for stroke prevention until publication of the negative results in the multinational EC/IC bypass trial32 in the mid-1980s. A vocal segment of the neurology community decried the apparent lack of evidence verifying the efficacy of carotid endarterectomy in stroke prevention, which led to a series of large-scale, prospective, randomized trials comparing carotid endarterectomy with medical therapy. In summary, there is now Level I evidence verifying the efficacy of carotid endarterectomy for stroke prevention in both symptomatic and asymptomatic patients.

Carotid Endarterectomy for Symptomatic Carotid Stenosis

In 1991, the results of the randomized North American Symptomatic Carotid Endarterectomy Trial (NASCET) of medical treatment or carotid endarterectomy were reported.33 All patients had either hemispheric retinal TIAs or nondisabling strokes within 120 days of entry into the trial and 70 to 99% stenosis in the symptomatic carotid artery. The actuarial risk of any ipsilateral stroke at 2 years was significantly lower at 9% in the 328 surgical patients versus 26% in the 331 medical patients. The data-safety monitoring committee halted further randomization given the widely disparate 18-month follow-up data. For major or fatal ipsilateral strokes, the risk was 2.5% for surgical patients versus 13.1% for medical patients (p < .001). When all strokes and deaths were included, carotid endarterectomy still was better than medical treatment. Subsequent follow-up studies from this trial indicated that the benefit of carotid endarterectomy in symptomatic patients extended to those with even moderate (50 to 69%) carotid artery lesions.34

The Veterans Affairs Cooperative Study of symptomatic carotid stenosis reported in 1991 results of randomizing 189 men with stenoses greater than 50% to medical or surgical treatment.35 After 1 year, there was a significant reduction in stroke or TIAs in the patients having carotid endarterectomy (7.7%) compared with medically treated patients (19.4%), with even more divergent results with carotid stenosis greater than 70%.

The European Carotid Surgery Trial randomized 2518 patients with nondisabling stroke, TIA, or retinal infarction in conjunction with ipsilateral carotid stenosis to medical or surgical treatment.36 For the 778 patients with stenoses of 70 to 99%, the cumulative risk of stroke at carotid endarterectomy of 7.5%, plus an additional late stroke rate at 3 years of 2.8%, was less than the 16.8% rate for medically treated patients. At 3 years the cumulative risk of operative death, operative stroke, ipsilateral ischemic stroke, and any other stroke was 12.3% for the surgical cohort versus 21.9% for the medical group (p < .01). Finally, the risk of fatal or disabling ipsilateral stroke at 3 years was 6.0% for the carotid endarterectomy patients versus 11.0% for the medical control patients (p < .05).

Although the benefit of endarterectomy in these studies was due in part to the high risk of stroke in medically treated patients, the results were significant even in an era when the 30-day combined stroke and death risk of endarterectomy was about 7.5%. Although the combined stroke and death risk of carotid endarterectomy is higher in symptomatic versus asymptomatic patients,37 the current combined risk is about 2 to 4%.23,28,38–44

Carotid Endarterectomy for Asymptomatic Carotid Stenosis

Early studies suggested a significant stroke risk reduction for carotid endarterectomy versus best medical therapy in asymptomatic patients.40,41 Contemporary randomized studies subsequently verified this position.

The Veterans Affairs Cooperative Study of asymptomatic carotid stenosis, defined as greater than 50% diameter reduction by angiography, randomized 444 men to medical or surgical treatment.42 At a mean follow-up of 4 years, the combined incidence of ipsilateral neurologic events was 8.0% for the surgical patients versus 20.6% for the medical patients (p < .001). The difference in stroke alone between the two groups (8 versus 20%) did not achieve statistical significance because of the study's sample size, nor was there a significant difference when all strokes and deaths were analyzed. Excessive late mortality (about 40% at 4 years in both groups) was caused largely by associated CAD. These mitigating factors limited definitive conclusions about the efficacy of carotid endarterectomy in asymptomatic patients in this trial.

In 1995, results of the Asymptomatic Carotid Atherosclerosis Study of 1662 patients randomized to surgical or medical treatment were published.27 At mean follow-up of 2.7 years, aggregate risk for ipsilateral stroke and any perioperative stroke or death for the surgical group was 5.1%, significantly lower than the rate of ipsilateral stroke of 11.0% for the medical group, a benefit limited to male patients. Critics suggested that the low combined stroke and death rate (2.3%) in the surgical patients was not representative of results across a broader spectrum of hospitals. However, low morbidity for carotid endarterectomy in asymptomatic patients has been verified in multiple large studies.43,44

In 2004, the Asymptomatic Carotid Surgery Trial (ACST),23 touted as the world's largest surgical trial from 126 hospitals in more than 30 countries, randomized over 3000 patients to carotid endarterectomy or medical therapy. Greater than 40% of patients had more than 3 years of follow-up. Risk of any stroke, any ipsilateral stroke, or any disabling stroke was halved in surgical patients, who had a combined stroke and death rate of about 3%. The time threshold to achieve statistical benefit, ie, cancel perioperative morbidity, by actuarial analysis was 2 years, suggesting that patients selected for endarterectomy should have a life expectancy of greater than 2 years. The only subgroup in which endarterectomy did not achieve statistical significance was in patients older than 75 years of age.

In summary, Level I evidence supports the advantage of carotid endarterectomy over medical management for patients with severe asymptomatic carotid artery stenoses. Of note, large contemporary studies verify the low perioperative morbidity with carotid endarterectomy, even across a spectrum of hospitals and surgeons. In a recent NSQIP study, whose methodology involved independent nurse reviewer adjudication of 30-day endpoints, some 4000 carotid endarterectomy procedures in both symptomatic and asymptomatic patients was accompanied by a 2.2% combined stroke and death risk.43

Following the success of percutaneous transluminal coronary angioplasty, particularly with adjunctive stenting, percutaneous interventionalists increasingly sought to treat carotid stenosis with angioplasty and stenting.45–47 Technical aspects of the procedure to guard against procedure-related stroke are the dominant concern with this procedure. Emerging reports (mostly from industry-sponsored trials) indicate that carotid stenting can produce equivalent outcomes to carotid endarterectomy.48–51 In one large series, the 30-day combined stroke and death rate was 7.4%, and most strokes were minor.52 Results improved with experience, and late stroke-free survival was comparable with that for carotid endarterectomy.

In 2004, a randomized trial of carotid endarterectomy versus stenting with routine embolic protection, designed as a “noninferiority” trial, ie, insufficiently powered to detect superiority of one treatment, concluded that carotid stenting was not inferior to carotid endarterectomy in high-risk patients.51 Study endpoints (composite death/stroke/MI at 30 days and 1 year), high 30-day combined stroke and death rate (5.7%) in asymptomatic patients, and small sample size limit the value of the data. Most large series and meta-analyses indicate a higher periprocedural complication rate for stenting versus endarterectomy.53–57 In the French carotid endarterectomy versus stenting study in patients with symptomatic, severe carotid stenosis, stenting was associated with a 2.2-fold increased risk of stroke or death at 30 days compared with endarterectomy. The data-safety monitoring committee halted the trial after randomizing 527 patients.58 The recently published International Carotid Stenting Study concluded that carotid endarterectomy, and not stenting, was the preferred treatment for symptomatic patients because of an unacceptable early stroke risk accompanying stenting.59 A Society of Vascular Surgery registry study with risk adjustment methodology reported a nearly three-fold increased risk of 30-day stroke, death, and myocardial infarction with stenting as opposed to carotid endarterectomy.54 Furthermore, published evidence documents an increased periprocedural risk of stroke after carotid stenting in elderly and symptomatic patients.55,57,60,61

Scant data are available about carotid stenting versus endarterectomy in patients requiring CABG. Investigators from the Cleveland Clinic compared patients treated with either carotid stenting before or carotid endarterectomy with open-heart surgery. After propensity scoring, the authors found no significant differences in combined stroke/death/MI in the two approaches.62

Given conflicting evidence to support combined carotid endarterectomy and CABG, not surprisingly many investigators have considered the strategy of antecedent carotid stenting, followed by interval CABG for combined disease. A logistic consideration in this strategy is the standard use of Clopidogrel with carotid stenting. One report from the Netherlands advocated such a strategy, but only if the CABG could be delayed for at least three weeks; overall death/stroke/myocardial infarction was still 8.7%.63 Two collective reviews reflect the difficulty of improving upon reported results with combined carotid endarterectomy and CABG, and/or the conservative posture with respect to asymptomatic carotid stenosis in patients requiring CABG. Naylor collected 11 studies with 760 carotid stent procedures performed at variable intervals before CABG. The cumulative 30-day stroke/death risk was 9.1%, stated to be quite similar to the authors' prior review of concomitant carotid endarterectomy and CABG.64,65 As in prior reports, that group supported a noninterventional approach in asymptomatic patients. Similarly, Guzman et al. reported a combined stroke/death rate of 12.3% for nearly 300 patients with carotid stenting followed by interval CABG performed at a mean of 32 days after the stenting. They concluded that the strategy of carotid stenting before CABG did not positively influence the stroke risk.66

Although this chapter is focused primarily on managing CABG patients who have concomitant carotid artery disease, some comment on the impact of CAD on short- and long-term risks of carotid endarterectomy patients is appropriate.

Incidence of Coronary Artery Disease in Carotid Endarterectomy Patients

Mackey and colleagues67 found that 53% of carotid endarterectomy patients had evidence of CAD by clinical history or electrocardiographic studies. Using thallium exercise testing in 106 carotid endarterectomy patients, Urbinati and colleagues68 found that 27 (25%) had significant defects on myocardial scanning. In 1985, the Cleveland Clinic reported the results of routine preoperative coronary angiography in 506 carotid endarterectomy patients.69 Only 7% of patients had normal coronary arteries, and 28% had mild to moderate CAD. However, 30% had advanced but compensated disease, 28% had severe, correctable disease, and 7% had severe, inoperable CAD.

Risk of Myocardial Ischemic Events

Short-Term Risks

The impact of CAD on short-term risks of carotid endarterectomy is well documented. In 1981, Hertzer and colleagues70 reported hospital mortality in 335 carotid endarterectomy patients of 1.8%; 60% of deaths were caused by CAD. In the Mackey study cited earlier, carotid endarterectomy patients with clinical CAD had an operative mortality of 1.5% and an MI rate of 4.3% compared with no mortality and an MI rate of 0.5% for patients without CAD.67 Although the frequent coexistence of CAD with carotid disease is often invoked as a principal cause of short- and long-term morbidity in carotid endarterectomy patients, the risk of perioperative MI vary with the risk profile of the cohort studied. For example, in the protected carotid artery stenting versus endarterectomy trial, 30-day non-Q wave MI occurred in 6.6%.51 In our cohort of more than 2000 carotid endarterectomy patients, the perioperative MI rate was 1.2%.28 A National Surgical Quality Improvement Program (NSQIP) database report of more than 13,000 endarterectomy procedures had a perioperative MI rate of 1.4%,71 similar to results from the ACST trial.23 In the Society for Vascular Surgery registry study myocardial infarction occurred in less than 1% of carotid endarterectomies.54 Clearly, improved care, mostly in the form of adjunctive medical therapy with beta blockers, statins and aspirin, has substantially lowered the risk of coronary ischemic events complicating carotid endarterectomy.

Long-Term Risks

Mackey's study of carotid endarterectomy reported the 5- and 10-year survival rates of patients with CAD to be 68.6 and 44.9%, respectively, versus 86.4 and 72.3% for patients with no CAD.67 Urbinati and colleagues reported the 7-year freedom from all cardiac events after carotid endarterectomy was 51% for patients with silent myocardial ischemia versus 98% for patients with normal thallium exercise testing.68

In the Hertzer study of 209 patients with clinically suspected CAD, 5-year mortality rate for hospital survivors was 27%, and 37% of late deaths were caused by MI.70 Actuarial survival at 11 years was significantly better for the patients with CAD who had bypass grafting. A later study from the same group of 329 carotid endarterectomy patients followed to 10 years confirmed that MI caused more late deaths (37%) than did stroke (15%).72 Again, 10-year survival was significantly better for patients having CABG.

In our Massachusetts General Hospital cohort of more than 2000 carotid endarterectomy patients treated between 1990 and 1999, 10-year actuarial survival was 45%. Among variables associated with increased late mortality, concomitant CAD [odds ratio (OR) 1.4; p = .0002] figured prominently.28

If one accepts that (1) uncorrected carotid stenosis increases the risk of stroke for patients with severe carotid and CAD who have only isolated CABG, (2) carotid endarterectomy is the indicated treatment for severe symptomatic and asymptomatic carotid stenosis, (3) CAD increases the early and late risk of death for carotid endarterectomy patients, and (4) CABG is an indicated treatment for CAD, then the important question becomes not the indication for but the timing of the two operative procedures.

Staged Carotid and Coronary Artery Operations

One approach is to perform the carotid endarterectomy and CABG operations as staged procedures. By convention, doing the carotid endarterectomy before coronary bypass grafting is referred to as a staged procedure, whereas doing the CABG before the carotid artery operation is called a reverse staged procedure.

Most advocates of a sequential operative approach to patients with severe combined disease usually do the carotid endarterectomy first if the patient is hemodynamically stable and not ischemic. Improvements in patient management, especially use of regional anesthesia, may allow safe initial isolated carotid endarterectomy. Data from several studies powered to detect an impact of regional anesthesia have verified that composite outcomes of stroke/death/ MI after carotid endarterectomy are reduced significantly with use of regional anesthesia.37,71 Alternatively, a large randomized study concluded that regional anesthesia for carotid endarterectomy had no significant impact on perioperative myocardial infarction when compared with general anesthesia.73 Depending on the timing of the two procedures, practical considerations, such as imminent need for the large doses of heparin required for cardiopulmonary bypass, airway and/or neck swelling, and the risk of perioperative coronary ischemic events, remain real issues.

For unstable cardiac patients, particularly those with asymptomatic carotid stenosis, some cardiac surgeons opt to perform initial myocardial revascularization followed by an interval carotid endarterectomy. The principal risk with this approach is the potential for neurologic complications either during or shortly after the myocardial revascularization.

Currently, we advocate concomitant carotid and coronary artery operations for virtually all patients with severe combined disease. However, in patients with severe bilateral carotid stenosis, a staged approach may be appropriate, especially if the patient is cardiovascularly stable. We occasionally treat the more severe of the two carotid artery lesions with initial isolated endarterectomy, followed by combined CABG and endarterectomy of the other carotid artery within a few days. Use of a reversed staged approach, namely, doing one carotid endarterectomy with myocardial revascularization followed several days later by the other carotid endarterectomy, is rare because of an increased stroke risk with reversed staged procedures (to be discussed below).

Concomitant Carotid and Coronary Artery Operations

In 1972, Bernhard and colleagues74 published the first report of successful combined carotid endarterectomy and CABG in 15 patients. The strategy of performing both operative procedures during one anesthetic is based on the premise that such an approach to severe combined disease ought to minimize cardiac events that frequently complicate isolated carotid endarterectomy and neurologic events that complicate isolated CABG.

Daily and colleagues75 reported that doing both operative procedures together is more cost effective than a staged or reversed staged approach, which require two anesthetics and can incur the additional costs of two hospitalizations.

Standard Approach

The usual operative technique for concomitant carotid endarterectomy and CABG has been to perform the carotid endarterectomy during harvesting of CAD conduits before cardiopulmonary bypass, the approach we use at our institution, where the carotid operation is performed by vascular surgeons as the cardiac surgical team harvests whatever saphenous vein or other conduits may be needed.

Technical aspects of carotid endarterectomy have evolved. Preoperative aspirin has been validated in large database studies.76 We use routine electroencephalographic monitoring, selective shunting, and either eversion endarterectomy (presuming no need for a shunt) or patch closure. Simple primary closure is associated with a higher rate of restenosis.77,78 After the carotid endarterectomy is completed, the neck incision is loosely approximated over a sponge. Final closure, usually over a plastic drain, is done after cardiopulmonary bypass is completed and heparinization is reversed.

Alternative Approaches

Minami and colleagues reported using some perceived advantages of cardiopulmonary bypass, namely, heparinization, hypothermia, and hemodynamic control, to perform carotid endarterectomy in 116 patients while on bypass for CABG.79 Operative mortality was 1.7%, and total stroke risk was 4.3%. Weiss and colleagues perform the carotid endarterectomy on bypass with systemic hypothermia to 20° C with the heart protected with cardioplegia.80 They had no neurologic events and one postoperative death in 23 patients. Theoretically, hypothermia on cardiopulmonary bypass provides an extra margin of ischemic protection for the brain during the carotid endarterectomy and avoids the need for intravascular shunting.

Whether performing the carotid and coronary artery operations on cardiopulmonary bypass saves total operative time is not proven, but it prolongs aortic occlusion and cardiopulmonary bypass times, something most cardiac surgeons would prefer to avoid. A deeper level of hypothermia is not favored by most cardiac surgeons, particularly as the trend toward using lesser degrees of hypothermia has become more popular.

Our postoperative management of patients following concomitant carotid endarterectomy and CABG does not differ importantly from that of patients having isolated myocardial revascularization. We believe that maintenance of a good coronary perfusion pressure and, by extension, good cerebral perfusion pressure in the early postoperative hours is beneficial. Early clearing of perioperative edema with diuresis is efficacious.

The routine anticoagulation protocol for our myocardial revascularization patients, aspirin begun within 6 hours of completion of the operation, is also adequate for patients with concomitant carotid endarterectomy. Permanent aspirin therapy is indicated for both parts of the concomitant procedure.

If a surgeon decides not to treat a severe carotid stenosis either with a staged approach or concomitant operation, the increased incidence of stroke in the early days after isolated myocardial revascularization seen with the reversed staged approach suggests that heparinization is appropriate once the acute bleeding risk of the CAB operation is past.

Early Results

Staged Carotid and Coronary Artery Operations

Several studies report the results of staged operations for concomitant carotid and CAD, but only one study randomized patients to concomitant or reversed staged operation. Hertzer et al. randomized subgroup of patients with unstable coronary syndromes and incidental asymptomatic carotid stenosis.81 Over 5 years they treated 275 patients with severe combined disease. Their criteria for carotid endarterectomy was symptomatic and/or severe (>70%) carotid artery disease. Only 24 (9%) of the patients had CAD that was stable enough to allow carotid endarterectomy before CABG. Of those 24 patients, 1 (4.2%) suffered a perioperative stroke after the carotid endarterectomy and died of an MI awaiting CABG. Symptomatic or severe bilateral carotid artery disease in 122 patients was treated with combined carotid and coronary artery operation with an operative mortality rate of 6.1% and a perioperative stroke rate of 7.1%.

The remaining 129 patients with unstable coronary symptoms and severe, unilateral, asymptomatic carotid stenoses were randomized to either a combined or a reversed staged operation. Patients having concomitant carotid and coronary operations had a mortality rate of 4.2% versus a combined rate of 5.3% for the two operations in the staged patients. Stroke rate in the concomitant operations was 2.8%, significantly lower than the 14% risk of the reversed staged operations (6.9% during the isolated CABG and 7.5% during the delayed isolated carotid endarterectomy). This randomized study emphasizes the advantage of concomitant operations over reversed staged procedures.

Several conclusions of this study were validated by a cumulative review from nearly 100 studies encompassing some 9000 patients. The authors noted that carotid endarterectomy very shortly after CABG was accompanied by an unacceptable stroke risk. They reported the stroke risk of the combined operation in their review was 4.6% and that of death/any stroke was 8.7%.65 These data are similar to other large administrative database studies (stroke/death of 9.6% for combined operation), although such studies are inherently flawed because details for the procedures being staged or combined are often imprecise.82

In 1999, Borger and colleagues performed a meta-analysis of nonrandomized observational studies from centers reporting results with both staged and concomitant operations.83 They identified a trend toward increased risk of stroke and death with combined operations. The results of this study need to be viewed with caution for several reasons. First, using meta-analysis to compare observational and nonrandomized studies limits its statistical power. Second, in most series, unstable patients had combined operations and stable patients had staged procedures. Third, the criterion for entry into these studies was operations completed, not intention to treat. Possibly some patients for whom a staged approach was planned were not studied because the second operation was never performed because of a poor result from the first procedure.

Concomitant Carotid and Coronary Artery Operations

Since the late 1970s, some surgeons in our group have taken an aggressive approach to patients with combined carotid and CAD, using concomitant operation as the standard approach. Staged operations were reserved for the patients with very stable CAD. Our first report in 1989 suggested that combined operation was safe (2% stroke or death risk). That study was among the first to document the disparate cardiac risk among patients having combined operations versus patients having isolated CABG.84

In 1995 we published our results of combined operations between 1979 and 1993 in the first 200 consecutive patients.85 Hospital mortality was 3.5%, MI 2.5%, and perioperative stroke 4.0%.

More recently, we published results of concomitant operation between 1979 and 2001 in 500 patients.86 Mean patient age was 69 years, about 6 years older than that for all CABG patients. Three-quarters of the patients had unstable angina pectoris, and 53% had prior MI. Although the distribution of single-, double-, and triple-vessel disease was as expected at 4%, 21%, and 75%, respectively, 42% of patients had significant left main CAD. Of the 500 patients, 329 (66%) were neurologically asymptomatic, 21% had transient ischemic attacks, and 13% had a prior stroke. Unilateral severe carotid stenosis was found in 336 patients (67%); 32% had disease in the contralateral carotid artery.

Urgent or emergency operations were required in 54% of patients; 3% were on the intra-aortic balloon preoperatively. The average number of grafts per patient was 3.7. Although only 50% of the first 200 patients received at least one mammary artery graft, 90% of the last 300 patients received a mammary artery graft.

Hospital mortality was 3.6%, MI was 2.0%, and stroke occurred in 4.6%. Of the 23 strokes, 12 were ipsilateral to the carotid endarterectomy and 11 contralateral or bilateral, suggesting that, in our experience, concomitant carotid endarterectomy and CABG have neutralized the impact of carotid stenosis as a risk factor for stroke during surgical myocardial revascularization.

Significant multivariate predictors of hospital death were preoperative TIAs, preoperative MI, and nonelective operation. Peripheral vascular disease predicted postoperative stroke. Significant predictors of prolonged postoperative hospital stay were failure to use a mammary artery graft, perioperative stroke, and advanced age.

Vermeulen and colleagues found that the only significant multivariate predictor of hospital death in 230 combined operations was left main CAD.87 Postoperative neurologic events were predicted by severe left ventricular dysfunction and preoperative neurologic events, either stroke or TIAs.

Series of concomitant carotid endarterectomy and CABG published since 1985 are in Table 23-2. These results contrast to reports using administrative data. Brown reported a 17.7% stroke risk for combined operations in Medicare patients in Midwestern states.88 In a Canadian study the combined risk of stroke and death for CABG alone was 4.9% versus 13% for combined carotid and coronary artery operations.89 However, data from the New York State Registry indicate that such results can be explained largely by the disparate cardiac risk profiles of the two patient groups. Ricotta and colleagues used propensity scoring to match risk-factor profiling and found no difference in combined stroke and death risk for the two operations after case-control matching.11 Finally, Cywinski et al., using similar methodology for patient matching, reported in a Cleveland Clinic series of combined operations versus isolated CABG that overall morbidity was higher for the concomitant carotid and coronary operations. Of interest, their study endpoints, in which significant differences were noted between the two groups including overall morbidity and mortality, did not find a significant difference in the risk of stroke.90

Late Results

Follow-up in our series of combined operations revealed the following 10-year actuarial freedoms from late events: death, 43%; MI, 87%; percutaneous transluminal coronary angioplasty, 92%; reoperative myocardial revascularization, 96%; total stroke, 85%; and ipsilateral stroke, 90%.86

Vermeulen and colleagues found their 10-year actuarial freedom from cardiac events to be 50%, from neurologic events to be 81%, and from all events to be 41%.87 The only significant multivariate predictors of late cardiac mortality were advanced age and severe left ventricular dysfunction.

In a study of 127 combined carotid and coronary operations, Rizzo et al. reported a 5-year survival rate of 70%, freedom from MI of 84%, and freedom from stroke of 88%.91 Survival was worse for patients with low ejection fractions. Late strokes were fewer in patients who were neurologically asymptomatic preoperatively, more common in patients who were transiently symptomatic, and most frequent in patients with prior stroke.

The risk of perioperative stroke following myocardial revascularization rises with the increasing age of CABG patients, and increasing age is accompanied by an increased incidence of carotid artery disease. Several studies have defined severe, uncorrected carotid stenosis as a major risk factor for perioperative stroke. Patients with carotid bruits or a history of ischemic neurologic events, plus patients who are 65 years old or older ought to have noninvasive carotid artery evaluation before CABG. Randomized trials have established the safety and efficacy of carotid endarterectomy as the most appropriate treatment for both symptomatic and asymptomatic severe carotid stenosis. Another randomized study has demonstrated the advantage of concomitant carotid endarterectomy and CABG over reversed staged operations. Thus, we advocate combined carotid and coronary artery operations for virtually all patients with severe concomitant coronary and carotid artery disease, which on their own merits would require treatment.