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Ann Thorac Surg 1996;62:1714-1723
© 1996 The Society of Thoracic Surgeons
Department of Thoracic and Cardiovascular Surgery, Lahey Hitchcock Medical Center, Burlington, Massachusetts
| Abstract |
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Methods. Preoperative, intraoperative, and postoperative clinical data were prospectively collected for 1,835 consecutive patients undergoing first-time isolated coronary artery bypass grafting between March 1990 and July 1995, 1,279 of whom had screening carotid ultrasonography. All patients with postoperative neurologic events were identified and reviewed in detail. Average patient age was 65.3 years (range, 33 to 92 years), and 9.3% (171 patients) had a prior permanent stroke or transient ischemic attack. Hospital and 30-day mortality was 2.2% (41 patients). Forty-five patients (2.5%) had a transient or permanent postoperative neurologic event. The data were analyzed by stepwise logistic regression to determine the independent predictors of both significant carotid stenosis and stroke.
Results. On multivariate analysis, the clinical predictors of significant carotid stenosis were age (p < 0.0001), diabetes (p = 0.0123), female sex (p = 0.0026), left main coronary stenosis greater than 60% (p < 0.0001), prior stroke or transient ischemic attack (p = 0.0008), peripheral vascular disease (p = 0.0001), prior vascular operation (p = 0.0068), and smoking (p < 0.0001). When all variables were evaluated for those patients who underwent noninvasive carotid artery screening, the independent predictors of postoperative neurologic event were prior stroke or transient ischemic attack (p < 0.0001), peripheral vascular disease (p = 0.0037), postinfarction angina pectoris (p = 0.0319), postoperative atrial fibrillation (p = 0.0014), carotid stenosis greater than 50% (p = 0.0029), cardiopulmonary bypass time (p = 0.0006), significant aortic atherosclerosis (p = 0.0054), postoperative amrinone or epinephrine use (p = 0.0054), and left ventricular ejection fraction less than 0.30 (p = 0.0744).
Conclusions. The etiology of postoperative stroke is multifactorial. Selective use of carotid ultrasonography is of value in identifying patients who are at greater risk of postoperative stroke independent of other variables and should be considered before coronary artery bypass grafting, particularly in patients with a history of neurologic event or peripheral vascular disease.
| Introduction |
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Continual improvements in myocardial preservation, cardiopulmonary bypass techniques, and postoperative care have allowed cardiac surgeons to perform increasingly complex procedures on older and sicker patients. Despite these achievements, and ironically in part because of them, postoperative stroke has emerged as a frustrating problem for the surgeon and an often devastating complication for patients. The role of extracranial cerebrovascular disease in the genesis of postoperative stroke and the utility of noninvasive carotid artery screening (NICS) in patients undergoing coronary artery bypass grafting (CABG) remain incompletely defined. This report examines our experience with NICS and stroke in patients undergoing CABG.
| Material and Methods |
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All patients in whom any neurologic symptoms developed during the hospitalization or within 30 days of discharge were identified by query of the computer database and by reviewing monthly morbidity and mortality reports. Hospital and outpatient records of all 77 such identified patients were reviewed in detail. Twenty patients who had transient confusion without any focal neurologic finding or new abnormality on computed tomographic or magnetic resonance brain imaging and whose symptoms were clearly attributable to medications, sleep deprivation, alcohol abuse, or metabolic causes were considered not to have sustained a stroke. One patient in whom a global encephalopathy developed without focal findings 1 week postoperatively in the setting of multiorgan system failure, hemodynamic instability, and a negative computed tomographic head scan was not regarded as having had a stroke. Also not included in the stroke group were 1 patient with embolic stroke secondary to native mitral valve endocarditis 30 days after CABG, 6 patients with ischemic optic neuropathy, 2 patients with visual symptoms secondary to pituitary tumor, and 2 patients with visual symptoms due to complications of diabetic retinopathy. After these exclusions, 45 patients were identified as having had a temporary or permanent focal or global neurologic defect. For the purposes of this analysis, patients who had a transient ischemic attack (TIA) or a reversible ischemic neurologic event were considered as having had a stroke (CVA).
Screening carotid ultrasonography was performed in 1,279 patients. Before September 1993, patients were evaluated with a continuous-wave Doppler scanner. Subsequently, studies were performed with a color duplex scanner (ATL Ultramark 9 HDI; Advanced Technology Laboratories, Bothel, WA). All cardiac operations were performed by five attending surgeons, three of whom obtained carotid ultrasonography routinely unless prohibited by the urgency of the patient's cardiac condition. Two surgeons employed ultrasonography selectively based on a history of prior stroke or TIA, advanced age, carotid bruits, or extensive peripheral vascular disease. The results of noninvasive imaging were graded on the following basis: no significant disease (<50% stenosis), moderate disease (50% to 80% stenosis), and severe disease (>80% stenosis). The quality of the ascending aorta at operation was recorded by the attending surgeon and was graded as showing no, mild, moderate, or severe disease. In the earlier time period of the study this qualitative assessment was based on the appearance of the aorta, the presence of palpable calcification, or the findings of intramural or intraluminal debris during creation of the proximal anastomoses. During the most recent 2 years, this clinical assessment has been supplemented by intraoperative transesophageal or epiaortic ultrasound in patients with abnormal appearing aortas.
All operations were performed using systemic hypothermia and cold blood cardioplegic arrest. Cardiopulmonary bypass flow rates were maintained between 2.0 and 2.4 Lmin-1m-2 and systemic pressures between 55 and 80 mm Hg. Systemic perfusion pressures were maintained at a higher range (70 to 80 mm Hg) in patients with untreated carotid stenoses. All distal coronary anastomoses were created first. Four of five surgeons generally fashioned proximal anastomoses after release of the aortic cross-clamp, and one surgeon uniformly created both proximal and distal anastomoses during a single period of aortic cross-clamping. Left ventricular venting was not routinely employed. Thirty-four patients underwent combined CABG and CE. The endarterectomy was performed by a separate vascular surgical team, before median sternotomy and during harvest of the saphenous vein. Arterial carotid shunts were used in all cases.
The following clinical variables were collected for the statistical analyses: preoperative continuous variables were age and left ventricular ejection fraction; preoperative categoric variables were age greater than 70 years, sex, hypertension, diabetes, tobacco use, chronic obstructive lung disease, preoperative renal dysfunction, New York Heart Association functional class, urgency of operation, postinfarction angina, peripheral vascular disease, prior vascular operation, history of abdominal aortic aneurysm, prior stroke or transient ischemic attack, preoperative NICS, degree of right and left carotid stenoses, presence of unilateral or bilateral NICS stenosis greater than 50%, presence of unilateral or bilateral NICS stenosis greater than 80%, aspirin use, intravenous heparin or nitroglycerin use, intraaortic balloon pump, intravenous pressor agents, left main coronary stenosis greater than 60%, and left ventricular ejection fraction less than 0.30. Intraoperative continuous variables were number of distal anastomoses, lowest esophageal temperature during cardiopulmonary bypass, and cardiopulmonary bypass time; intraoperative categoric variables were use of the internal thoracic artery, technique of proximal anastomosis (single period of aortic cross-clamping versus partial aortic exclusion with side-biting clamp), ascending aortic quality, and need for femoral arterial cannulation. The only postoperative continuous variable was number of inotropes/pressors used; postoperative categoric variables were more than two inotropes/pressors, use of amrinone or epinephrine, perioperative myocardial infarction, renal failure, respiratory failure, need for tracheostomy, atrial fibrillation, stroke, and death. Quantitative data are presented as mean ± standard deviation. Univariate comparisons between groups were calculated by the unpaired t test, Fisher's exact test,
2 test, or the one-way or two-way analysis of variance, as appropriate. All probabilities are two-tailed, with a p value less than 0.05 regarded as significant. Independent predictors were determined by stepwise logistic regression analysis. All variables were used for the multivariate analysis, but only variables with a p value less than 0.1 were entered during computational stepping of the model. All computations were performed using the BMDP statistical software package (BMDP Statistical Software, Inc, Los Angeles, CA).
| Results |
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One thousand two hundred seventy-nine patients underwent NICS. The prevalence of carotid stenoses, prior brain ischemic event, and postoperative stroke is shown in Table 2
. The majority of patients (79.5%, 1,017 of 1,279 patients) had no significant carotid disease. However, 88 of these 1,017 patients (8.7%) had a history of prior stroke or TIA. Two hundred sixty-two of the 1,279 patients studied by NICS (20.5%) had a greater than 50% stenosis of at least one internal carotid artery, and 23 patients (1.8%) had bilateral stenoses greater than 80%. The prevalence of carotid stenoses in patients undergoing NICS and the occurrence of postoperative stroke by degree of carotid disease is shown in Figure 1
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Prior stroke or TIA was present in 32 of the 172 patients with unilateral stenosis. Four of these patients (12.5%) underwent combined CABG and CE, and none had postoperative stroke. Five of 28 patients (17.9%) with unilateral stenosis and prior symptoms who did not undergo combined CABG and CE had a postoperative event. One patient had development of significant postoperative hypotension and sustained a stroke contralateral to an occluded carotid artery. The ipsilateral carotid artery showed no significant disease. One patient sustained an occipital stroke in the setting of atrial fibrillation, aortic atherosclerosis, and both carotid and vertebral artery stenoses. The third patient sustained a stroke contralateral to a moderate carotid stenosis and ipsilateral to a prior stroke. One transient and one permanent event were ipsilateral to a known carotid stenosis. Thus, in only these latter 2 patients would a combined CABG and CE have possibly prevented a postoperative stroke.
Bilateral carotid stenoses greater than 50% were present in 90 of the 262 patients. Fifty-five of these patients (61%) had no prior symptoms. Of this subgroup, 10 patients underwent combined CABG and CE, and 1 patient (10%) had a postoperative stroke ipsilateral to the CE. Of the 45 patients who did not have combined CABG and CE, 3 (6.7%) sustained a postoperative stroke. Two of the strokes (4.4%) could be attributed to the carotid disease, and the third patient's stroke was compatible with an embolic event 4 days postoperatively and temporally associated with conversion from atrial fibrillation to sinus rhythm.
Thirty-five of the 90 patients with bilateral significant stenoses had a history of prior stroke or TIA. Sixteen had combined CABG and CE, and postoperative stroke developed in 3 (18.8%). One stroke was contralateral to the CE in the setting of an ipsilateral high-grade stenosis, postoperative hypotension, and low output syndrome. One stroke occurred ipsilateral to the CE. The third patient showed diffuse bihemispheric and cerebellar infarcts presumably of embolic origin. Nineteen of the 35 patients with bilateral stenoses and prior symptoms did not have CABG and CE, and postoperative stroke developed in 5 (26.3%). Three of these strokes (15.8%) were attributable to carotid disease.
Four separate models were used to evaluate the independent predictors of stroke by multivariate analysis (Table 6
). Two models each (all variables versus preoperative variables) were created for the entire group of 1,835 patients and for the group of 1,279 patients who underwent NICS. Because of the small number of total strokes, it was not possible to make valid statistical comparisons according to (1) the impact of degree of stenosis and (2) unilateral or bilateral involvement. Hence, during stepwise logistic regression analysis the multivariate models were allowed to select whether either a unilateral stenosis greater than 50% or bilateral carotid stenoses greater than 50% was the best predictor. Postinfarction angina, vascular disease, prior stroke, or TIA were the independent predictors common to all four models. Atrial fibrillation, cardiopulmonary bypass time, degree of aortic atherosclerosis, and the use of amrinone or epinephrine were also significant independent predictors of stroke when all variables were used. Left ventricular ejection fraction less than 0.30 was also a significant independent predictor of stroke in both multivariate models that evaluated preoperative variables only.
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| Comment |
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With the exception of warm heart surgery [2], improvements in perfusion techniques have diminished the role of cardiopulmonary bypass in the genesis of clinically evident postoperative neurologic dysfunction. The majority of strokes in the current era are due to atherosclerosis of the ascending aorta, cerebrovascular disease, and macroemboli of cardiac origin. Our multivariate analyses support this multifactorial etiology and have shown the presence of peripheral vascular disease, a prior stroke or TIA, significant carotid stenoses, postinfarction angina, longer cardiopulmonary bypass time, aortic atherosclerosis, postoperative atrial fibrillation, the use of amrinone or epinephrine, and left ventricular ejection fraction less than 0.30 to be significant independent predictors of postoperative stroke in CABG patients.
Our patients with a history of CVA or TIA had a 10% incidence of postoperative stroke. Rorick and Furlan [3] and Berens and colleagues [4] found similar incidences of postoperative stroke (13.4% and 5%, respectively) in their cardiac surgery patients with a prior neurologic event. Reed and colleagues [5] noted that patients with previous stroke were at a sixfold increased risk of postoperative stroke.
Aortic atherosclerosis is increasingly recognized as a major risk factor for stroke. Although paleness of the ascending aorta or thickening of the adventitial tissue can be an indicator of troublesome atherosclerosis we, as have others [68], found aortic palpation to be an unreliable indicator of the degree of disease. We used transesophageal or epiaortic ultrasonography during the last 2 years of our study and then on a selective basis only. Undoubtedly, this has led to an underestimation of the significance of this variable in our patient population. Wareing and associates [9] have demonstrated a 19% incidence of moderate to severe aortic atherosclerosis in their patients older than 50 years who were evaluated ultrasonographically. Amarenco and colleagues [10] and, most recently, the French Study of Aortic Plaques in Stroke Group [11] have shown aortic arch plaque to be a significant predictor of recurrent brain infarction in patients older than 60 years.
Advanced age at operation has been shown to be associated with ascending aortic atherosclerosis and increased incidence of stroke by numerous investigators [8, 1214]. Although its significance was eclipsed by other factors in our multivariate analyses, we found age to be a significant univariate predictor of stroke. Indeed, stroke occurred in 8.6% of our patients older than 80 years.
We found postinfarction angina to be a significant independent predictor of stroke. Patients with postinfarction angina can have more perioperative hemodynamic instability, which can potentially influence the stroke rate. But it is also equally plausible that due to their recent infarction, patients with postinfarction angina are at increased risk for occult left ventricular mural thrombus. We were unable to assess this issue because appropriate echographic data were available in a minority of our patients. However, Lynn and associates [15] and Bull and colleagues [16] have shown left ventricular mural thrombus to be an independent risk factor for stroke. Postinfarction angina being a risk factor in our patients, therefore, may represent a surrogate for the risk factor of echographic evidence of mural thrombus found by these investigators. Similarly, patients with diminished left ventricular function are at risk for stroke by virtue of mural thrombus or the more frequent requirement for postoperative inotropic support. In our institution, the use of amrinone and epinephrine is reserved for more pronounced degrees of myocardial dysfunction. The attendant hemodynamic instability and hypoperfusion in such settings as well as the vasoconstriction seen with higher doses of
-adrenergic agents can result in diminished cerebral blood flow. Four of our patients sustained a stroke in such a setting.
Postoperative stroke occurred in 4.6% of our patients with atrial fibrillation compared with 1.5% of patients without atrial fibrillation. Taylor and associates [17] reported a 7% incidence of postoperative stroke in patients with atrial fibrillation, and this association has also been noted by others [5, 15]. Whether this risk can be diminished by an aggressive regimen of early anticoagulation for postoperative atrial fibrillation remains to be determined by a prospective study.
The management of patients with coexisting coronary and carotid arterial disease remains unsettled. Drawing definitive conclusions from published series is confounded by their varying patient compositions, management strategies, and lengths of postoperative follow-up. In this current era of cost-effective medicine, the practicing cardiac surgeon is faced with two difficult and complementary questions: who should undergo carotid arterial screening, and what should be done with the information obtained? Concerning the first question, our patients had a mean age of 66 years, and a carotid stenosis greater than 50% was found in 20%. Eight percent of patients had a stenosis greater than 80%. Berens and associates [4] found similar results in a prospective study of NICS in 1,087 patients older than 65 years and demonstrated a 17% prevalence of carotid stenosis greater than 50% and a 5.9% prevalence of stenosis greater than 80%. Similar incidences of between 17% and 22% have been found by others [18, 19]. Our multivariate analysis demonstrated age, female sex, diabetes, tobacco, peripheral vascular disease or operation, prior CVA or TIA, significant left main coronary artery stenosis, and the need for preoperative inotropes to be the significant independent predictors of a significant carotid stenosis. With the exception of diabetes and inotropes, these risk factors are essentially identical to those reported by Berens and associates [4]. Preoperative noninvasive screening would be expected, therefore, to have the highest yield in patients with one or more of these factors.
Until a properly designed, prospective, randomized, multiinstitutional study can provide definitive answers to the second question regarding which patients benefit from combined operations, we must extrapolate from the results of this and other previously reported studies. Akins and associates [20] and Daily and colleagues [21] have recently shown that combined CABG and CE operations can be done safely, although it must be remembered that previously reported stroke rates have ranged from 0% to 14% [22, 23].
It is generally, but not universally, accepted that patients with active symptoms referable to both carotid and coronary disease are best managed by combined CABG and CE. However, the benefits of combined CABG and CE for patients with unilateral or bilateral asymptomatic carotid stenoses remain unclear as there is no unequivocal evidence to suggest that they are at increased risk of stroke in the perioperative period. Of interest in this regard is our group of 137 patients with an asymptomatic unilateral significant stenosis who did not undergo combined CABG and CE. None of the four strokes that occurred in this group were referable to the carotid stenosis. Two were due to atheroemboli from the ascending aorta and two were due to atrial fibrillation-related cardiac emboli. Also of interest is the fate of the 90 patients who had bilateral significant stenoses. Fifty-five of these 90 had no prior or current symptoms of stroke or TIA. Of the 10 who underwent combined operation, 1 patient (10%) had a postoperative stroke ipsilateral to the carotid endarterectomy. A postoperative stroke developed in only 3 of 45 patients (6.7%) who underwent CABG without CE, and we could implicate carotid disease in only 2 (4.4%) of these.
Hertzer and associates [24] noted a peri-CABG stroke incidence of 6.9% in the subset of patients with unilateral asymptomatic carotid stenosis greater than 70% and unstable coronary disease randomized to CABG followed by delayed CE. Barnes and colleagues [25] and Schultz and associates [26] concluded that peri-CABG stroke risk was not increased in patients with significant asymptomatic carotid stenoses, although Barnes and colleagues found these patients to be at increased risk of neurologic event during late follow-up. Gerraty and associates [27] prospectively evaluated perioperative stroke risk in a series of 358 patients undergoing a peripheral vascular operation or CABG. A moratorium was placed on CE for patients with asymptomatic stenoses of 50% or greater. None of the 53 patients (15 of whom had stenosis of 80% or greater) with asymptomatic stenoses of 50% or greater sustained a stroke. Two of 213 CABG patients sustained small infarcts, and in neither patient was there an associated significant carotid stenosis. Gerraty and associates concluded that the risk of perioperative stroke due to asymptomatic carotid stenosis is low and does not justify prophylactic carotid endarterectomy. Our experience with stroke in patients who have a unilateral asymptomatic carotid stenosis would appear to support this conclusion. The risk of perioperative stroke referable to carotid disease is only 4.4% in our patients with asymptomatic bilateral disease managed with CABG alone. However, our data are not sufficient for us to draw any specific conclusions regarding the merits of CABG and CE in this group of patients. In the absence of more definitive information, we generally reserve combined CABG and CE for those asymptomatic patients with high-grade bilateral disease or with a significant stenosis and a contralateral occlusion.
In summary, the etiology of postoperative stroke is multifactorial, and any factor or a combination of factors may play a role in any given patient. The majority of strokes are caused by embolic phenomena from an atherosclerotic aorta or from the heart. Cerebrovascular disease is a causative factor of postoperative stroke in approximately 30% of our patients. A history of prior stroke or TIA, peripheral vascular disease, advanced age, female sex, and significant left main coronary stenosis are associated with a greater likelihood of harboring a significant carotid stenosis. We believe that selective use of carotid ultrasonography can help in identifying patients who are at greater risk of postoperative stroke and should be considered prior to CABG, particularly in patients with a history of prior neurologic event or peripheral vascular disease.
| Acknowledgments |
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| Footnotes |
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Address reprint requests to Dr D'Agostino, Department of Thoracic and Cardiovascular Surgery, Lahey Hitchcock Medical Center, 41 Mall Rd, Burlington, MA 01805.
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G. D. Trachiotis and A. J. Pfister Management Strategy for Simultaneous Carotid Endarterectomy and Coronary Revascularization Ann. Thorac. Surg., October 1, 1997; 64(4): 1013 - 1018. [Abstract] [Full Text] |
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