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The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database
Journal of Clinical Neuroscience xxx (xxxx) xxx
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Clinical study
The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database Varun S. Shah a, Daniel Kreatsoulas b, David Dornbos III b, Santino Cua a, Ciarán J. Powers b,⇑ a b
The Ohio State University College of Medicine, Columbus, OH USA The Ohio State University Wexner Medical Center, Department of Neurological Surgery, Columbus, OH USA
a r t i c l e
i n f o
Article history: Received 20 June 2019 Accepted 26 January 2020 Available online xxxx Keywords: ACS-NSQIP Atherosclerosis Carotid Endarterectomy
a b s t r a c t Carotid artery stenosis accounts for up to 20% of ischemic strokes. Since the 1950 s, one of the primary surgical treatment for this condition is carotid endarterectomy (CEA). Because of improvement of medical therapy for carotid artery atherosclerosis and the increased use of carotid artery stents, CEA is indicated if the risk of stroke and death are low. The goal of this study is to characterize the impact of pre-operative stroke and stroke risk factors on post-operative CEA patient outcomes, using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Vascular Module on CEA. Using the Targeted Vascular Module of the ACS-NSQIP, 22,116 patients who underwent CEA were identified from 2011 to 2016. Univariate analysis and multivariable logistic regression analyses were conducted to identify significant risk factors that predispose patients to stroke. Patients with pre-operative stroke comprise 42.1% of the group, with post-operative stroke being the second most common complication (2.1%). Pre-operative stroke patients were also at a higher risk for transient ischemic attacks, post-operative restenosis, post-operative distal embolization, and other complications. Patients with pre-operative risk factors, including stroke or stroke-like symptoms, high risk physiologic factors, high risk anatomic factors, and contralateral internal carotid artery stenosis were at a higher risk of developing post-operative stroke and other complications. Patients with these pre-operative risk factors should be closely monitored for post-operative complications in an effort to improve patient outcomes. Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction Carotid artery stenosis is the underlying etiology of nearly 20% of all ischemic stroke, typically due to an atherosclerotic plaque in the proximal internal carotid artery (ICA) at the carotid bifurcation [1,2]. Although the role of endovascular treatment and carotid artery stenting has expanded significantly, carotid endarterectomy (CEA) remains the primary treatment modality for this condition, aimed to prevent future stroke and death in patients with carotid artery stenosis. Both the North American Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) established a benefit for CEA in stroke prevention over medical therapy [3–6]. Since these trials, improved medical therapy and the use of carotid artery stents has partially decreased the use of CEA, but CEA remains the standard of care in certain patients when no contraindications are present [3,7–10]. Factors known to pre-dispose CEA patients to post-operative stroke ⇑ Corresponding author at: The Ohio State University Wexner Medical Center, N-1004 Doan Hall, 410 W. 10th Avenue, Columbus, OH 43210, USA. E-mail address: [email protected] (C.J. Powers).
include age > 80 years old, race, a history of stroke or transient ischemic attack (TIA), severe disability, coronary artery disease, and contralateral carotid stenosis [11]. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) includes over 700 participating hospitals, all of which contribute to data collection. ACSNSQIP collects data on 30-day post-operative complications in all surgical patients at participating hospitals, accounting for over 270 variables. This database uses data from medical charts and is collected by trained surgical chart reviewers at each hospital. These reviewers follow a strict data collection protocol in an effort to maintain uniformity among hospitals. In the Targeted Vascular Module within this database, data variables, determined by a team of vascular surgeons, are collected for all CEA and carotid artery stenting procedures. A recent study by Pothof et al. used this database to provide an update on post-operative complications in CEA patients, stratified by presenting neurological symptoms. They found that patients undergoing CEA following presentation with a pre-operative stroke were more likely to suffer from 30-day stroke and death compared to patients presenting with preoperative transient ischemic attack (TIA) and ocular TIA [3]. This
https://doi.org/10.1016/j.jocn.2020.01.077 0967-5868/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
study aims to expand on these findings through use of the ACSNSQIP CEA database, to confirm the findings of the previous study, and further discuss specific factors influencing the incidence of stroke in the peri-operative time period. 2. Methods This study did not require approval from the Institutional Review Board at our health center since ACS-NSQIP does not include patient identifiers in their data set. For this reason, patient consent was not required. Data was collected from the 2011 to 2016 databases. Every patient in the CEA database only underwent CEA; therefore, every patient was included unless there was incomplete data. The primary variable used to analyze patients in this study was the status of pre-operative symptoms. In the database, patients were grouped into 4 pre-operative symptom categories: 1) asymptomatic, 2) amaurosis fugax, 3) hemispheric transient ischemic attack, and 4) stroke. For the present study, symptomatic patients were grouped into a singular category named pre-operative stroke or stroke-like symptoms. These patients were then compared to those in the asymptomatic preoperative group. Primary outcome was the incidence of 30-day post-operative stroke. Secondary outcome variables included the incidence of myocardial infarction (MI) or arrhythmia, TIA or amaurosis fugax, restenosis, and distal embolization. The definition of total complications is the sum of those present in the primary and secondary outcomes. For individual complications and the factors that predisposed to them, univariate logistic regression was performed, and odds ratios were calculated. This was performed for each complication, as well as total complications. The variables in univariate analysis with a p-value of 0.2 or below were utilized to create multivariable logistic regression analyses. The ACS-NSQIP CEA database did not define high risk anatomical factors or high-risk physiologic risk factors. For the purpose of this paper, the authors chose the definition provided by the Centers for Medicare and Medicaid Services (CMS). High risk anatomy factors were defined as contralateral ICA occlusion, a high carotid bifurcation above the angle of the mandible, prior neck surgery, and prior neck irradiation [12]. High-risk physiology has been defined by CMS as age > 80 years, congestive heart failure, and severe COPD [12]. A p value of < 0.05 was considered statistically significant, and all statistical analyses were performed using SPSS statistical software (IBM), version 25.
shunt only (501 cases, 2.3%). A total of 9,303 patients in this series had pre-operative stroke or stroke-like symptoms (42.1%). Many of the pre-operative characteristics were observed with differing relative frequency when comparing patients with pre-operative stroke symptoms to those without (Table 2), including procedure type, physiologic and anatomic risk factors, and pre-operative antiplatelet and beta blocker use. Patients with a pre-operative stroke had a higher relative percentage of pre-operative beta-blocker use and more high-risk anatomic and physiologic factors, although they had a slightly lower relative incidence of pre-operative aspirin use. These underlying variations are unsurprising given that standard treatment following stroke includes antiplatelet drugs, and those with high-risk physiologic factors would be expected to carry a predisposition to stroke, especially if not on aspirin. The most common complication following CEA in the whole cohort was cranial nerve injury (588 patients, 2.7%), followed by post-operative stroke (473 patients, 2.1%) and post-operative myocardial infarction or arrhythmia (381 patients, 1.7%). Complication rates following CEA in the pre-operative stroke group were 3.2% for stroke (301 patients), 1.7% for post-operative myocardial infarction and arrhythmia (161 patients), and 1.6% for TIA or amaurosis fugax (146 patients). Given that the primary outcome was aimed at risk of 30-day stroke risk, further analysis for cranial nerve injury was not performed. None of the other variables (TIA or amaurosis fugax, post-operative acute occlusion, postoperative restenosis, distal embolization) occurred in greater than 1% of the patient population. There was a total of 1,898 complications that occurred in 1,602 patients (7.24%) in this cohort. The post-operative stroke rate for those without pre-operative symptoms was 1.34%, whereas those with pre-operative stroke had a post-operative stroke rate of 3.24%. Factors that significantly influenced the incidence of post-operative stroke (Table 3) in univariate analysis included pre-operative stroke (odds ratio (OR) 2.457, 95% confidence interval (CI) 2.034 – 2.970, p < 0.0001), high anatomic risk factors (OR 1.484, 95% CI 1.156–1.907, p = 0.002), and presence of moderate (OR 1.329, 95% CI 1.066 – 1.658, p = 0.011), severe (OR 2.020, 95% CI 1.473 – 2.770, p < 0.0001), or complete (OR 1.764, 95% CI 1.164–2.672, p = 0.007) contralateral ICA stenosis on Doppler ultrasound studies. In multivariable logistical regression model, these effects remained significant for preoperative stroke (OR 2.507, 95% CI 2.041 – 3.079, p < 0.0001), moderate ICA stenosis (OR 1.367, 95% CI 1.096 – 1.707, p = 0.006), and severe ICA stenosis (OR 1.967, 95% CI 1.432 – 2.703, p < 0.0001). The significant factors on univariate analysis that predict postoperative MI or arrhythmia (Table 4) include presence of high-risk physiologic factors (OR 2.035, 95% CI 1.436–2.885, p < 0.0001),
3. Results After review of the database a total of 22,116 cases were obtained (28 patients were excluded for incomplete data). A breakdown of the different classifications of carotid endarterectomy based on procedural classification is shown in Table 1. The most commonly performed procedure was CEA with patch angioplasty (10,020 cases, 45.3%), and the least often performed was CEA with
Table 1 Breakdown of CEA procedures included in the ACS-NSQIP CEA database. Procedure
No. of Cases
Percent
Carotid Endarterectomy Carotid Endarterectomy w/ patch angioplasty Carotid Endarterectomy w/shunt Carotid Endarterectomy w/patch angioplasty & shunt Eversion Carotid Endarterectomy Not documented Total
2640 10,020 501 6899
11.9 45.3 2.3 31.2
2028 28 22,116
9.2 0.1 100.0
Table 2 Pre-Operative variables in patients with or without a pre-operative stroke.
High Risk Physiologic Factors High Risk Anatomic Factors Procedural Classification CEA only CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA Antiplatelet Use Beta Blocker Use
No Pre-operative Stroke, n = 12,813
Preoperative Stroke, n = 9303
P-value
553 (4.32%)
543 (5.84%)
<0.0001
1386 (10.82%)
1127 (12.11%)
0.003
1366 (10.66%) 6045 (47.18%)
1274 (13.69%) 3975 (42.73%)
<0.0001 <0.0001
248 (1.94%) 3820 (29.81%)
253 (2.72%) 3079 (33.10%)
<0.0001 <0.0001
1309 (10.22%) 11,468 (89.50%) 7445 (48.11%)
719 (7.73%) 8190 (88.04%) 4617 (49.63%)
<0.0001 0.001 <0.0001
CEA = carotid endarterectomy.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx Table 3 Effects of patient characteristics on incidence of post-operative stroke.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
2.457 (2.034–2.970)
<0.0001
2.507 (2.041–3.079)
<0.0001
0.883 1.126 0.997 0.742 1.355 1.484 0.892 0.990 0.966
(0.661–1.179) (0.614–2.066) (0.740–1.345) (0.488–1.130) (0.937–1.961) (1.156–1.907) (0.676–1.178) (0.786–1.246) (0.805–1.160)
0.399 0.701 0.986 0.164 0.107 0.002 0.422 0.930 0.711
1.371 (0.935–2.010) 1.312 (0.972–1.772)
0.107 0.076
0.807 (0.374–1.740) 0.748 (0.350–1.598) 1.059 (0.366–3.066)
0.584 0.453 0.915
1.329 (1.066–1.658) 2.020 (1.473–2.770) 1.764 (1.164–2.672)
0.011 <0.0001 0.007
1.367 (1.096–1.707) 1.967 (1.432–2.703) 1.536 (0.962–2.452)
0.006 <0.0001 0.072
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
1.008 (0.821–1.237)
0.939
1.144 1.389 1.030 1.023 2.035 1.559 1.131 1.123 1.808
0.435 0.337 0.871 0.922 <0.0001 0.001 0.475 0.394 <0.0001
1.858 (1.293–2.669) 1.478 (1.080–2.023)
0.001 0.015
1.723 (1.372–2.165)
<0.0001
1.368 (1.090–1.717) 0.885 (0.565–1.384) 0.944 (0.545–1.636)
0.007 0.592 0.838
CEA = carotid endarterectomy; ICA = internal carotid artery. Bold P-values are significant.
Table 4 Effects of patient characteristics on post-operative MI/Arrhythmia.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
(0.816–1.605) (0.710–2.716) (0.721–1.472) (0.646–1.620) (1.436–2.885) (1.186–2.050) (0.807–1.585) (0.860–1.464) (1.455–2.248)
1.177 (0.431–3.214) 1.108 (0.409–2.998) 0.791 (0.175–3.569)
0.75 0.84 0.76
1.419 (1.132–1.780) 0.951 (0.609–1.487) 1.246 (0.754–2.059)
0.002 0.827 0.391
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
presence of high-risk anatomic factors (OR 1.559, 95% CI 1.186– 2.050, p = 0.001), presence of pre-operative beta blocker use (OR 1.808, 95% CI 1.455–2.248, p < 0.0001), and presence of moderate contralateral ICA stenosis on Doppler ultrasound (OR 1.419, 95% CI 1.132–1.780, p = 0.002). In multivariable analysis, these four factors were found to be independent risk factors for post-operative MI: high-risk physiologic factors (OR 1.858, 95% CI 1.293–2.669, p = 0.001), high-risk anatomic factors (OR 1.478, 95% CI 1.080– 2.023, p = 0.015), pre-operative beta blocker use (OR 1.723, 95% CI 1.372–2.165, p = <0.0001), and moderate contralateral ICA stenosis (OR 1.368, 95% CI 1.090–1.717, p = 0.007). Factors associated with post-operative TIA/amaurosis fugax (Table 5) that were significant in univariate analysis included pre-operative stroke symptoms (OR 2.903, 95% CI 2.180–3.864, p < 0.0001), CEA with patch angioplasty (OR 0.673, 95% CI 0.459– 0.987, p = 0.043), CEA with patch angioplasty and shunt (OR 0.659, 95% CI 0.438 – 0.990, p = 0.045), eversion CEA (OR 0.384, 95% CI 0.195–0.754, p = 0.005), presence of high-risk anatomic
factors (OR 1.464, 95% CI 1.012–2.116, p = 0.043) and severe contralateral ICA stenosis (OR 2.558, 95% CI 1.687–3.879, p < 0.0001). In multivariable analysis, independent variables predictive of post-operative TIA included pre-operative stroke (OR 2.388, 95% CI 1.763–3.233, p < 0.0001), patients who received CEA with patch angioplasty only (OR 0.618, 95% CI 0.409–0.934, p = 0.022), CEA with patch angioplasty and shunt (OR 0.637, 95% CI 0.413–0.981, p = 0.041), high-risk anatomic factors (OR 1.678, 95% CI 1.117–2.522, p = 0.013), and patients with severe contralateral ICA stenosis (OR 2.435, 95% CI 1.600–3.704, p < 0.0001). Further analysis of the incidence of restenosis following CEA found that only the presence of severe contralateral ICA stenosis (OR 2.653, 95% CI 1.290 – 5.455, p = 0.008) was significant on univariate analysis. Severe contralateral ICA stenosis was also significant following multivariable analysis (OR 2.696, 95% CI 1.309–5.555, p = 0.007). Although other factors, such as the presence of pre-operative stroke (OR 1.529, 95% CI 0.979–2.386, p = 0.062) and moderate contralateral ICA stenosis (OR 1.596,
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Table 5 Effects of patient characteristics on Post-operative TIA.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
2.903 (2.180–3.864)
<0.0001
2.388 (1.763–3.233)
<0.0001
0.673 1.287 0.659 0.384 1.437 1.464 0.716 0.792 1.042
(0.459–0.987) (0.617–2.683) (0.438–0.990) (0.195–0.754) (0.848–2.437) (1.012–2.116) (0.491–1.045) (0.576–1.088) (0.796–1.365)
0.043 0.501 0.045 0.005 0.178 0.043 0.083 0.15 0.763
0.618 1.361 0.637 0.503
(0.409–0.934) (0.644–2.878) (0.413–0.981) (0.253–1.002)
0.022 0.419 0.041 0.051
1.678 (1.117–2.522) 0.702 (0.468–1.053)
0.013 0.087
0.632 (0.229–1.749) 0.618 (0.227–1.681) 0.261 (0.029–2.355)
0.377 0.346 0.232
1.201 (0.864–1.669) 2.558 (1.687–3.879) 0.994 (0.459–2.150)
0.276 <0.0001 0.987
1.230 (0.884–1.711) 2.435 (1.600–3.704) 0.725 (0.316–1.662)
0.22 <0.0001 0.448
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
95% CI 0.934–2.728, p = 0.087) approached significance on univariate analysis, they did not demonstrate statistical significance on multivariable analysis. In evaluating risk factors for distal embolization, potential factors included presence of pre-operative stroke symptoms (OR 2.377, 95% CI 1.329–4.251, p = 0.004) and high-risk anatomic factors (OR 2.537, 95% CI 1.321–4.872, p = 0.005). On multivariable analysis, both variables were found to be independently associated with distal emboli following CEA with a 2-fold increase in this complication in both pre-operative stroke symptoms (OR 2.209, 95% CI 1.223–3.958, p = 0.008) and high-risk anatomic factors (OR 2.334, 95% CI 1.215–4.485, p = 0.011). Logistic regression analysis was also used to assess the risk factors associated with developing any complication following CEA (Table 6). Univariate analysis revealed that pre-operative stroke, CEA with patch angioplasty with or without a shunt, high-risk physiologic or anatomic factors, pre-operative use of beta blockers, and moderate or severe contralateral ICA stenosis were significantly associated with a higher risk of complications. On multivariable analysis, pre-operative stroke (OR 1.453, 95% CI 1.303–1.620, p < 0.0001), CEA with patch angioplasty and shunt (OR 1.226, 95%
CI 1.011–1.486, p = 0.038), high-risk anatomic factors (OR 1.640, 95% CI 1.396–1.927, p < 0.0001), pre-operative beta-blocker use (OR 1.194, 95% CI 1.069–1.927, p = 0.003) and severe contralateral ICA stenosis (OR 1.295, 95% CI 1.067–1.573, p = 0.009) were independent predictors of complication development. Patients with high-risk anatomic risk factors or pre-operative stroke carried the highest overall odds of experiencing a complication, compared to patients with other risk factors.
4. Discussion This study found that CEA patients with pre-operative stroke symptoms experience a significantly higher rate of post-operative stroke compared to those patients who were asymptomatic. This may be partially due to plaque morphology in pre-operative stroke patients [3]. A study by Howard et al. identified several features, including plaque inflammation, large lipid core and low fibrous content, that appear to be associated with an increased ipsilateral stroke risk within 30 days of CEA [13]. High-risk anatomy factors also predispose patients to post-operative stroke. Although the
Table 6 Effects of patient characteristics on incidence of any complication.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
1.495 (1.350–1.656)
<0.0001
1.453 (1.303–1.620)
<0.0001
1.202 1.277 1.232 0.795 1.320 1.627 1.154 1.054 1.166
0.037 0.182 0.023 0.075 0.01 <0.0001 0.098 0.427 0.003
1.185 1.453 1.226 0.908 1.238 1.640
0.074 0.047 0.038 0.484 0.06 <0.0001
(1.012–1.430) (0.892–1.828) (1.030–1.474) (0.618–1.023) (1.069–1.631) (1.416–1.868) (0.974–1.368) (0.925–1.202) (1.052–1.293)
1.272 (0.749–2.161) 1.265 (0.748–2.138) 1.606 (0.813–3.174)
0.373 0.381 0.173
1.133 (1.005–1.277) 1.363 (1.124–1.653) 1.234 (0.959–1.588)
0.042 0.002 0.102
(0.984–1.428) (1.006–2.099) (1.011–1.486) (0.694–1.189) (0.991–1.547) (1.396–1.927)
1.194 (1.069–1.927)
0.002
1.120 (0.993–1.264) 1.295 (1.067–1.573) 0.868 (0.657–1.148)
0.065 0.009 0.322
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
ACS-NSQIP CEA database did not include a definition of anatomic risk factors, the Centers for Medicare and Medicaid Services (CMS) define high-risk as contralateral ICA occlusion, a high carotid bifurcation above the angle of the mandible, prior neck surgery, and prior neck irradiation [12]. The inflow and outflow areas of the carotid bifurcation are critical sites that may modulate hemodynamic forces that lead to atherosclerosis [14]. Additionally, flow studies have shown a smaller ICA to common carotid artery ratio can cause oscillatory shear stress at the outer portion of the ICA, which can lead to intimal thickening and stenosis [14–17]. Moderate, severe, and complete occlusion of the contralateral ICA increased the risk of post-operative stroke in this population, likely due to diminished cerebral flow following ipsilateral clamping. Despite this finding, numerous studies have not shown contralateral ICA stenosis to be a significant risk factor [18]. Although physiologic risk factors were not significantly associated with post-operative stroke in this study, other studies were able to find this relationship. Analysis of the larger ACS-NSQIP database showed chronic corticosteroid use, preoperative acute renal failure, paraplegia, impaired sensorium, and declining functional status were all risk factors for post-operative stroke in symptomatic CEA patients, all physiological predispositions that were not previously highlighted [19]. This study also showed debilitating chronic obstructive pulmonary disease (COPD) as a risk factor for post-operative stroke in the symptomatic CEA population [19]. Other physiological risk factors identified elsewhere showed history of angina, peripheral vascular disease, dialysis, and age to be associated with increased stroke rates in symptomatic CEA patients as well [19–23]. Patients with pre-operative stroke were just as likely as asymptomatic patients to suffer from a post-operative MI or arrhythmia. Unsurprisingly, risk factors that predisposed patients to MI or arrhythmia included high-risk physiologic factors, high-risk anatomic factors, pre-operative beta-blocker use, and moderate contralateral ICA stenosis. Although not explicitly delineated by the ACS-NSQIP CEA database, high-risk physiology has been defined by CMS as age >80 years, congestive heart failure, and severe COPD [12]. Furthermore, common high-risk physiologic factors predisposing to stroke include hypertension, smoking, diabetes, hyperlipidemia, and kidney disease with concomitant coronary artery disease [24,25]. Patients with these risk factors should be monitored closely in an effort to prevent complications. The preoperative use of beta-blockers is likely explained by pre-existing coronary artery disease or other cardiac co-morbidities. A Canadian study found an association between pre-operative beta-blocker use and cerebral ischemia in CEA, but found no change in intraoperative hemodynamics [26]. Contralateral ICA stenosis contributing to post-operative MI and arrhythmia may potentially be secondary to the longer duration of surgery due to shunt placement, or may simply be evidence of an overall increase in vascular disease severity. Numerous factors were associated with post-operative TIA and amaurosis fugax. Pre-operative stroke symptoms increased the risk for these patients nearly 3-fold. Procedural classification, specifically CEA with patch angioplasty with or without shunt and eversion CEA, increased the risk of post-operative TIA. While the underlying reasons are unclear, specific care should be taken in observing patients for TIA symptoms following these specific procedures. Surprisingly while pre-operative antiplatelet use approached significance, it remained non-significant, even on multivariable analysis. This finding fits with numerous studies, which show that peri-operative antiplatelet therapy decreases inhospital stroke and death risk [27]. While antiplatelet use in CEA is associated with an increased risk of hemorrhage and CEA revision, it remains an important modality to reduce peri-operative stroke [27–29].
5
The only factor that was associated with post-operative restenosis was severe contralateral ICA stenosis. While there are currently no studies assessing the risk of restenosis with contralateral ICA stenosis, this likely indicates more severe underlying vascular disease with a greater predisposition to inflammation, plaque development and thrombosis. Post-operative distal emboli were seen with increased frequency in patients with pre-operative stroke symptoms and high-risk anatomic factors. Although these factors cannot be controlled for or eliminated pre-operatively, care should be taken to minimize their potential impact on peri-operative stroke and can be used to counsel patients regarding CEA risks. There is a vested interest in improving outcomes for stroke patients. Previous studies have demonstrated the need to reduce post-operative complications in stroke patients in order to reduce long-term costs and mortality [30,31]. This need is exacerbated by the continued high stroke incidence and growing costs of strokerelated care. This study identifies potential opportunities for improving stroke care, mitigating post-operative complications and ultimately, reducing costs associated with stroke care. This study has several limitations. This is a retrospective review of a large database, which relies on accurate and thorough input of information. This study design is not able to eliminate bias, but the size of the cohort is able to partially ameliorate this by potentially reducing sampling error. In the context of a large database study it has the potential to exacerbate aggregation error and errors associated with the systematic exclusion of variables. The large sample size may also add to the significance of some results seen, and some of these 1% – 2% differences may not be seen as clinically important. Additionally, given the constraints of the ACS-NSQIP database, long-term outcomes (Modified Rankin Scale and National Institute of Health Stroke Scale) beyond 30 days cannot be evaluated, which may under report the number of complications. Additionally, analysis was limited to the variables the ACS-NSQIP CEA database provided and was not able to be all encompassing, thus leaving out variables that have been highlighted in other studies, including studies that analyzed the larger ACS-NSQIP database. Furthermore, this database did not include demographic variables, therefore analysis of this was not able to be undertaken. There is a potential for collinearity within this data, but the purpose of the multivariate analysis was to control for this. Despite these limitations, this study represents one of the largest patient cohorts use to evaluate post-operative CEA complications. 5. Conclusion Patients undergoing CEA with pre-operative stroke symptoms or with factors that predispose them to stroke are more likely to suffer from post-operative stroke or stroke-like symptoms in the perioperative time period. Additionally, patients with high-risk anatomic and physiologic factors are at an increased risk of stroke postoperatively. This study further reveals an association between contralateral ICA stenosis and post-operative stroke. Patients with these pre-operative risk factors should be closely monitored for postoperative complications in an effort to improve patient outcomes. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2020.01.077.
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Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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Clinical study
The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database Varun S. Shah a, Daniel Kreatsoulas b, David Dornbos III b, Santino Cua a, Ciarán J. Powers b,⇑ a b
The Ohio State University College of Medicine, Columbus, OH USA The Ohio State University Wexner Medical Center, Department of Neurological Surgery, Columbus, OH USA
a r t i c l e
i n f o
Article history: Received 20 June 2019 Accepted 26 January 2020 Available online xxxx Keywords: ACS-NSQIP Atherosclerosis Carotid Endarterectomy
a b s t r a c t Carotid artery stenosis accounts for up to 20% of ischemic strokes. Since the 1950 s, one of the primary surgical treatment for this condition is carotid endarterectomy (CEA). Because of improvement of medical therapy for carotid artery atherosclerosis and the increased use of carotid artery stents, CEA is indicated if the risk of stroke and death are low. The goal of this study is to characterize the impact of pre-operative stroke and stroke risk factors on post-operative CEA patient outcomes, using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Vascular Module on CEA. Using the Targeted Vascular Module of the ACS-NSQIP, 22,116 patients who underwent CEA were identified from 2011 to 2016. Univariate analysis and multivariable logistic regression analyses were conducted to identify significant risk factors that predispose patients to stroke. Patients with pre-operative stroke comprise 42.1% of the group, with post-operative stroke being the second most common complication (2.1%). Pre-operative stroke patients were also at a higher risk for transient ischemic attacks, post-operative restenosis, post-operative distal embolization, and other complications. Patients with pre-operative risk factors, including stroke or stroke-like symptoms, high risk physiologic factors, high risk anatomic factors, and contralateral internal carotid artery stenosis were at a higher risk of developing post-operative stroke and other complications. Patients with these pre-operative risk factors should be closely monitored for post-operative complications in an effort to improve patient outcomes. Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction Carotid artery stenosis is the underlying etiology of nearly 20% of all ischemic stroke, typically due to an atherosclerotic plaque in the proximal internal carotid artery (ICA) at the carotid bifurcation [1,2]. Although the role of endovascular treatment and carotid artery stenting has expanded significantly, carotid endarterectomy (CEA) remains the primary treatment modality for this condition, aimed to prevent future stroke and death in patients with carotid artery stenosis. Both the North American Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) established a benefit for CEA in stroke prevention over medical therapy [3–6]. Since these trials, improved medical therapy and the use of carotid artery stents has partially decreased the use of CEA, but CEA remains the standard of care in certain patients when no contraindications are present [3,7–10]. Factors known to pre-dispose CEA patients to post-operative stroke ⇑ Corresponding author at: The Ohio State University Wexner Medical Center, N-1004 Doan Hall, 410 W. 10th Avenue, Columbus, OH 43210, USA. E-mail address: [email protected] (C.J. Powers).
include age > 80 years old, race, a history of stroke or transient ischemic attack (TIA), severe disability, coronary artery disease, and contralateral carotid stenosis [11]. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) includes over 700 participating hospitals, all of which contribute to data collection. ACSNSQIP collects data on 30-day post-operative complications in all surgical patients at participating hospitals, accounting for over 270 variables. This database uses data from medical charts and is collected by trained surgical chart reviewers at each hospital. These reviewers follow a strict data collection protocol in an effort to maintain uniformity among hospitals. In the Targeted Vascular Module within this database, data variables, determined by a team of vascular surgeons, are collected for all CEA and carotid artery stenting procedures. A recent study by Pothof et al. used this database to provide an update on post-operative complications in CEA patients, stratified by presenting neurological symptoms. They found that patients undergoing CEA following presentation with a pre-operative stroke were more likely to suffer from 30-day stroke and death compared to patients presenting with preoperative transient ischemic attack (TIA) and ocular TIA [3]. This
https://doi.org/10.1016/j.jocn.2020.01.077 0967-5868/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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study aims to expand on these findings through use of the ACSNSQIP CEA database, to confirm the findings of the previous study, and further discuss specific factors influencing the incidence of stroke in the peri-operative time period. 2. Methods This study did not require approval from the Institutional Review Board at our health center since ACS-NSQIP does not include patient identifiers in their data set. For this reason, patient consent was not required. Data was collected from the 2011 to 2016 databases. Every patient in the CEA database only underwent CEA; therefore, every patient was included unless there was incomplete data. The primary variable used to analyze patients in this study was the status of pre-operative symptoms. In the database, patients were grouped into 4 pre-operative symptom categories: 1) asymptomatic, 2) amaurosis fugax, 3) hemispheric transient ischemic attack, and 4) stroke. For the present study, symptomatic patients were grouped into a singular category named pre-operative stroke or stroke-like symptoms. These patients were then compared to those in the asymptomatic preoperative group. Primary outcome was the incidence of 30-day post-operative stroke. Secondary outcome variables included the incidence of myocardial infarction (MI) or arrhythmia, TIA or amaurosis fugax, restenosis, and distal embolization. The definition of total complications is the sum of those present in the primary and secondary outcomes. For individual complications and the factors that predisposed to them, univariate logistic regression was performed, and odds ratios were calculated. This was performed for each complication, as well as total complications. The variables in univariate analysis with a p-value of 0.2 or below were utilized to create multivariable logistic regression analyses. The ACS-NSQIP CEA database did not define high risk anatomical factors or high-risk physiologic risk factors. For the purpose of this paper, the authors chose the definition provided by the Centers for Medicare and Medicaid Services (CMS). High risk anatomy factors were defined as contralateral ICA occlusion, a high carotid bifurcation above the angle of the mandible, prior neck surgery, and prior neck irradiation [12]. High-risk physiology has been defined by CMS as age > 80 years, congestive heart failure, and severe COPD [12]. A p value of < 0.05 was considered statistically significant, and all statistical analyses were performed using SPSS statistical software (IBM), version 25.
shunt only (501 cases, 2.3%). A total of 9,303 patients in this series had pre-operative stroke or stroke-like symptoms (42.1%). Many of the pre-operative characteristics were observed with differing relative frequency when comparing patients with pre-operative stroke symptoms to those without (Table 2), including procedure type, physiologic and anatomic risk factors, and pre-operative antiplatelet and beta blocker use. Patients with a pre-operative stroke had a higher relative percentage of pre-operative beta-blocker use and more high-risk anatomic and physiologic factors, although they had a slightly lower relative incidence of pre-operative aspirin use. These underlying variations are unsurprising given that standard treatment following stroke includes antiplatelet drugs, and those with high-risk physiologic factors would be expected to carry a predisposition to stroke, especially if not on aspirin. The most common complication following CEA in the whole cohort was cranial nerve injury (588 patients, 2.7%), followed by post-operative stroke (473 patients, 2.1%) and post-operative myocardial infarction or arrhythmia (381 patients, 1.7%). Complication rates following CEA in the pre-operative stroke group were 3.2% for stroke (301 patients), 1.7% for post-operative myocardial infarction and arrhythmia (161 patients), and 1.6% for TIA or amaurosis fugax (146 patients). Given that the primary outcome was aimed at risk of 30-day stroke risk, further analysis for cranial nerve injury was not performed. None of the other variables (TIA or amaurosis fugax, post-operative acute occlusion, postoperative restenosis, distal embolization) occurred in greater than 1% of the patient population. There was a total of 1,898 complications that occurred in 1,602 patients (7.24%) in this cohort. The post-operative stroke rate for those without pre-operative symptoms was 1.34%, whereas those with pre-operative stroke had a post-operative stroke rate of 3.24%. Factors that significantly influenced the incidence of post-operative stroke (Table 3) in univariate analysis included pre-operative stroke (odds ratio (OR) 2.457, 95% confidence interval (CI) 2.034 – 2.970, p < 0.0001), high anatomic risk factors (OR 1.484, 95% CI 1.156–1.907, p = 0.002), and presence of moderate (OR 1.329, 95% CI 1.066 – 1.658, p = 0.011), severe (OR 2.020, 95% CI 1.473 – 2.770, p < 0.0001), or complete (OR 1.764, 95% CI 1.164–2.672, p = 0.007) contralateral ICA stenosis on Doppler ultrasound studies. In multivariable logistical regression model, these effects remained significant for preoperative stroke (OR 2.507, 95% CI 2.041 – 3.079, p < 0.0001), moderate ICA stenosis (OR 1.367, 95% CI 1.096 – 1.707, p = 0.006), and severe ICA stenosis (OR 1.967, 95% CI 1.432 – 2.703, p < 0.0001). The significant factors on univariate analysis that predict postoperative MI or arrhythmia (Table 4) include presence of high-risk physiologic factors (OR 2.035, 95% CI 1.436–2.885, p < 0.0001),
3. Results After review of the database a total of 22,116 cases were obtained (28 patients were excluded for incomplete data). A breakdown of the different classifications of carotid endarterectomy based on procedural classification is shown in Table 1. The most commonly performed procedure was CEA with patch angioplasty (10,020 cases, 45.3%), and the least often performed was CEA with
Table 1 Breakdown of CEA procedures included in the ACS-NSQIP CEA database. Procedure
No. of Cases
Percent
Carotid Endarterectomy Carotid Endarterectomy w/ patch angioplasty Carotid Endarterectomy w/shunt Carotid Endarterectomy w/patch angioplasty & shunt Eversion Carotid Endarterectomy Not documented Total
2640 10,020 501 6899
11.9 45.3 2.3 31.2
2028 28 22,116
9.2 0.1 100.0
Table 2 Pre-Operative variables in patients with or without a pre-operative stroke.
High Risk Physiologic Factors High Risk Anatomic Factors Procedural Classification CEA only CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA Antiplatelet Use Beta Blocker Use
No Pre-operative Stroke, n = 12,813
Preoperative Stroke, n = 9303
P-value
553 (4.32%)
543 (5.84%)
<0.0001
1386 (10.82%)
1127 (12.11%)
0.003
1366 (10.66%) 6045 (47.18%)
1274 (13.69%) 3975 (42.73%)
<0.0001 <0.0001
248 (1.94%) 3820 (29.81%)
253 (2.72%) 3079 (33.10%)
<0.0001 <0.0001
1309 (10.22%) 11,468 (89.50%) 7445 (48.11%)
719 (7.73%) 8190 (88.04%) 4617 (49.63%)
<0.0001 0.001 <0.0001
CEA = carotid endarterectomy.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx Table 3 Effects of patient characteristics on incidence of post-operative stroke.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
2.457 (2.034–2.970)
<0.0001
2.507 (2.041–3.079)
<0.0001
0.883 1.126 0.997 0.742 1.355 1.484 0.892 0.990 0.966
(0.661–1.179) (0.614–2.066) (0.740–1.345) (0.488–1.130) (0.937–1.961) (1.156–1.907) (0.676–1.178) (0.786–1.246) (0.805–1.160)
0.399 0.701 0.986 0.164 0.107 0.002 0.422 0.930 0.711
1.371 (0.935–2.010) 1.312 (0.972–1.772)
0.107 0.076
0.807 (0.374–1.740) 0.748 (0.350–1.598) 1.059 (0.366–3.066)
0.584 0.453 0.915
1.329 (1.066–1.658) 2.020 (1.473–2.770) 1.764 (1.164–2.672)
0.011 <0.0001 0.007
1.367 (1.096–1.707) 1.967 (1.432–2.703) 1.536 (0.962–2.452)
0.006 <0.0001 0.072
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
1.008 (0.821–1.237)
0.939
1.144 1.389 1.030 1.023 2.035 1.559 1.131 1.123 1.808
0.435 0.337 0.871 0.922 <0.0001 0.001 0.475 0.394 <0.0001
1.858 (1.293–2.669) 1.478 (1.080–2.023)
0.001 0.015
1.723 (1.372–2.165)
<0.0001
1.368 (1.090–1.717) 0.885 (0.565–1.384) 0.944 (0.545–1.636)
0.007 0.592 0.838
CEA = carotid endarterectomy; ICA = internal carotid artery. Bold P-values are significant.
Table 4 Effects of patient characteristics on post-operative MI/Arrhythmia.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
(0.816–1.605) (0.710–2.716) (0.721–1.472) (0.646–1.620) (1.436–2.885) (1.186–2.050) (0.807–1.585) (0.860–1.464) (1.455–2.248)
1.177 (0.431–3.214) 1.108 (0.409–2.998) 0.791 (0.175–3.569)
0.75 0.84 0.76
1.419 (1.132–1.780) 0.951 (0.609–1.487) 1.246 (0.754–2.059)
0.002 0.827 0.391
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
presence of high-risk anatomic factors (OR 1.559, 95% CI 1.186– 2.050, p = 0.001), presence of pre-operative beta blocker use (OR 1.808, 95% CI 1.455–2.248, p < 0.0001), and presence of moderate contralateral ICA stenosis on Doppler ultrasound (OR 1.419, 95% CI 1.132–1.780, p = 0.002). In multivariable analysis, these four factors were found to be independent risk factors for post-operative MI: high-risk physiologic factors (OR 1.858, 95% CI 1.293–2.669, p = 0.001), high-risk anatomic factors (OR 1.478, 95% CI 1.080– 2.023, p = 0.015), pre-operative beta blocker use (OR 1.723, 95% CI 1.372–2.165, p = <0.0001), and moderate contralateral ICA stenosis (OR 1.368, 95% CI 1.090–1.717, p = 0.007). Factors associated with post-operative TIA/amaurosis fugax (Table 5) that were significant in univariate analysis included pre-operative stroke symptoms (OR 2.903, 95% CI 2.180–3.864, p < 0.0001), CEA with patch angioplasty (OR 0.673, 95% CI 0.459– 0.987, p = 0.043), CEA with patch angioplasty and shunt (OR 0.659, 95% CI 0.438 – 0.990, p = 0.045), eversion CEA (OR 0.384, 95% CI 0.195–0.754, p = 0.005), presence of high-risk anatomic
factors (OR 1.464, 95% CI 1.012–2.116, p = 0.043) and severe contralateral ICA stenosis (OR 2.558, 95% CI 1.687–3.879, p < 0.0001). In multivariable analysis, independent variables predictive of post-operative TIA included pre-operative stroke (OR 2.388, 95% CI 1.763–3.233, p < 0.0001), patients who received CEA with patch angioplasty only (OR 0.618, 95% CI 0.409–0.934, p = 0.022), CEA with patch angioplasty and shunt (OR 0.637, 95% CI 0.413–0.981, p = 0.041), high-risk anatomic factors (OR 1.678, 95% CI 1.117–2.522, p = 0.013), and patients with severe contralateral ICA stenosis (OR 2.435, 95% CI 1.600–3.704, p < 0.0001). Further analysis of the incidence of restenosis following CEA found that only the presence of severe contralateral ICA stenosis (OR 2.653, 95% CI 1.290 – 5.455, p = 0.008) was significant on univariate analysis. Severe contralateral ICA stenosis was also significant following multivariable analysis (OR 2.696, 95% CI 1.309–5.555, p = 0.007). Although other factors, such as the presence of pre-operative stroke (OR 1.529, 95% CI 0.979–2.386, p = 0.062) and moderate contralateral ICA stenosis (OR 1.596,
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Table 5 Effects of patient characteristics on Post-operative TIA.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
2.903 (2.180–3.864)
<0.0001
2.388 (1.763–3.233)
<0.0001
0.673 1.287 0.659 0.384 1.437 1.464 0.716 0.792 1.042
(0.459–0.987) (0.617–2.683) (0.438–0.990) (0.195–0.754) (0.848–2.437) (1.012–2.116) (0.491–1.045) (0.576–1.088) (0.796–1.365)
0.043 0.501 0.045 0.005 0.178 0.043 0.083 0.15 0.763
0.618 1.361 0.637 0.503
(0.409–0.934) (0.644–2.878) (0.413–0.981) (0.253–1.002)
0.022 0.419 0.041 0.051
1.678 (1.117–2.522) 0.702 (0.468–1.053)
0.013 0.087
0.632 (0.229–1.749) 0.618 (0.227–1.681) 0.261 (0.029–2.355)
0.377 0.346 0.232
1.201 (0.864–1.669) 2.558 (1.687–3.879) 0.994 (0.459–2.150)
0.276 <0.0001 0.987
1.230 (0.884–1.711) 2.435 (1.600–3.704) 0.725 (0.316–1.662)
0.22 <0.0001 0.448
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
95% CI 0.934–2.728, p = 0.087) approached significance on univariate analysis, they did not demonstrate statistical significance on multivariable analysis. In evaluating risk factors for distal embolization, potential factors included presence of pre-operative stroke symptoms (OR 2.377, 95% CI 1.329–4.251, p = 0.004) and high-risk anatomic factors (OR 2.537, 95% CI 1.321–4.872, p = 0.005). On multivariable analysis, both variables were found to be independently associated with distal emboli following CEA with a 2-fold increase in this complication in both pre-operative stroke symptoms (OR 2.209, 95% CI 1.223–3.958, p = 0.008) and high-risk anatomic factors (OR 2.334, 95% CI 1.215–4.485, p = 0.011). Logistic regression analysis was also used to assess the risk factors associated with developing any complication following CEA (Table 6). Univariate analysis revealed that pre-operative stroke, CEA with patch angioplasty with or without a shunt, high-risk physiologic or anatomic factors, pre-operative use of beta blockers, and moderate or severe contralateral ICA stenosis were significantly associated with a higher risk of complications. On multivariable analysis, pre-operative stroke (OR 1.453, 95% CI 1.303–1.620, p < 0.0001), CEA with patch angioplasty and shunt (OR 1.226, 95%
CI 1.011–1.486, p = 0.038), high-risk anatomic factors (OR 1.640, 95% CI 1.396–1.927, p < 0.0001), pre-operative beta-blocker use (OR 1.194, 95% CI 1.069–1.927, p = 0.003) and severe contralateral ICA stenosis (OR 1.295, 95% CI 1.067–1.573, p = 0.009) were independent predictors of complication development. Patients with high-risk anatomic risk factors or pre-operative stroke carried the highest overall odds of experiencing a complication, compared to patients with other risk factors.
4. Discussion This study found that CEA patients with pre-operative stroke symptoms experience a significantly higher rate of post-operative stroke compared to those patients who were asymptomatic. This may be partially due to plaque morphology in pre-operative stroke patients [3]. A study by Howard et al. identified several features, including plaque inflammation, large lipid core and low fibrous content, that appear to be associated with an increased ipsilateral stroke risk within 30 days of CEA [13]. High-risk anatomy factors also predispose patients to post-operative stroke. Although the
Table 6 Effects of patient characteristics on incidence of any complication.
Pre-operative Stroke Symptoms Procedural Classification CEA with patch angioplasty CEA with shunt CEA with patch angioplasty and shunt Eversion CEA High Physiologic Risk Factors High Anatomic Risk Factors Pre-operative Antiplatelet Use Pre-operative Statin Use Pre-operative Beta Blocker Use Ipsilateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion Contralateral ICA Stenosis Moderate (50–79%) Severe (80–99%) Total Occlusion
Univariate Odds Ratio
P-value
Multivariable Odds Ratio
P-value
1.495 (1.350–1.656)
<0.0001
1.453 (1.303–1.620)
<0.0001
1.202 1.277 1.232 0.795 1.320 1.627 1.154 1.054 1.166
0.037 0.182 0.023 0.075 0.01 <0.0001 0.098 0.427 0.003
1.185 1.453 1.226 0.908 1.238 1.640
0.074 0.047 0.038 0.484 0.06 <0.0001
(1.012–1.430) (0.892–1.828) (1.030–1.474) (0.618–1.023) (1.069–1.631) (1.416–1.868) (0.974–1.368) (0.925–1.202) (1.052–1.293)
1.272 (0.749–2.161) 1.265 (0.748–2.138) 1.606 (0.813–3.174)
0.373 0.381 0.173
1.133 (1.005–1.277) 1.363 (1.124–1.653) 1.234 (0.959–1.588)
0.042 0.002 0.102
(0.984–1.428) (1.006–2.099) (1.011–1.486) (0.694–1.189) (0.991–1.547) (1.396–1.927)
1.194 (1.069–1.927)
0.002
1.120 (0.993–1.264) 1.295 (1.067–1.573) 0.868 (0.657–1.148)
0.065 0.009 0.322
CEA = carotid endarterectomy; ICA = internal carotid artery Bold P-values are significant.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
V.S. Shah et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
ACS-NSQIP CEA database did not include a definition of anatomic risk factors, the Centers for Medicare and Medicaid Services (CMS) define high-risk as contralateral ICA occlusion, a high carotid bifurcation above the angle of the mandible, prior neck surgery, and prior neck irradiation [12]. The inflow and outflow areas of the carotid bifurcation are critical sites that may modulate hemodynamic forces that lead to atherosclerosis [14]. Additionally, flow studies have shown a smaller ICA to common carotid artery ratio can cause oscillatory shear stress at the outer portion of the ICA, which can lead to intimal thickening and stenosis [14–17]. Moderate, severe, and complete occlusion of the contralateral ICA increased the risk of post-operative stroke in this population, likely due to diminished cerebral flow following ipsilateral clamping. Despite this finding, numerous studies have not shown contralateral ICA stenosis to be a significant risk factor [18]. Although physiologic risk factors were not significantly associated with post-operative stroke in this study, other studies were able to find this relationship. Analysis of the larger ACS-NSQIP database showed chronic corticosteroid use, preoperative acute renal failure, paraplegia, impaired sensorium, and declining functional status were all risk factors for post-operative stroke in symptomatic CEA patients, all physiological predispositions that were not previously highlighted [19]. This study also showed debilitating chronic obstructive pulmonary disease (COPD) as a risk factor for post-operative stroke in the symptomatic CEA population [19]. Other physiological risk factors identified elsewhere showed history of angina, peripheral vascular disease, dialysis, and age to be associated with increased stroke rates in symptomatic CEA patients as well [19–23]. Patients with pre-operative stroke were just as likely as asymptomatic patients to suffer from a post-operative MI or arrhythmia. Unsurprisingly, risk factors that predisposed patients to MI or arrhythmia included high-risk physiologic factors, high-risk anatomic factors, pre-operative beta-blocker use, and moderate contralateral ICA stenosis. Although not explicitly delineated by the ACS-NSQIP CEA database, high-risk physiology has been defined by CMS as age >80 years, congestive heart failure, and severe COPD [12]. Furthermore, common high-risk physiologic factors predisposing to stroke include hypertension, smoking, diabetes, hyperlipidemia, and kidney disease with concomitant coronary artery disease [24,25]. Patients with these risk factors should be monitored closely in an effort to prevent complications. The preoperative use of beta-blockers is likely explained by pre-existing coronary artery disease or other cardiac co-morbidities. A Canadian study found an association between pre-operative beta-blocker use and cerebral ischemia in CEA, but found no change in intraoperative hemodynamics [26]. Contralateral ICA stenosis contributing to post-operative MI and arrhythmia may potentially be secondary to the longer duration of surgery due to shunt placement, or may simply be evidence of an overall increase in vascular disease severity. Numerous factors were associated with post-operative TIA and amaurosis fugax. Pre-operative stroke symptoms increased the risk for these patients nearly 3-fold. Procedural classification, specifically CEA with patch angioplasty with or without shunt and eversion CEA, increased the risk of post-operative TIA. While the underlying reasons are unclear, specific care should be taken in observing patients for TIA symptoms following these specific procedures. Surprisingly while pre-operative antiplatelet use approached significance, it remained non-significant, even on multivariable analysis. This finding fits with numerous studies, which show that peri-operative antiplatelet therapy decreases inhospital stroke and death risk [27]. While antiplatelet use in CEA is associated with an increased risk of hemorrhage and CEA revision, it remains an important modality to reduce peri-operative stroke [27–29].
5
The only factor that was associated with post-operative restenosis was severe contralateral ICA stenosis. While there are currently no studies assessing the risk of restenosis with contralateral ICA stenosis, this likely indicates more severe underlying vascular disease with a greater predisposition to inflammation, plaque development and thrombosis. Post-operative distal emboli were seen with increased frequency in patients with pre-operative stroke symptoms and high-risk anatomic factors. Although these factors cannot be controlled for or eliminated pre-operatively, care should be taken to minimize their potential impact on peri-operative stroke and can be used to counsel patients regarding CEA risks. There is a vested interest in improving outcomes for stroke patients. Previous studies have demonstrated the need to reduce post-operative complications in stroke patients in order to reduce long-term costs and mortality [30,31]. This need is exacerbated by the continued high stroke incidence and growing costs of strokerelated care. This study identifies potential opportunities for improving stroke care, mitigating post-operative complications and ultimately, reducing costs associated with stroke care. This study has several limitations. This is a retrospective review of a large database, which relies on accurate and thorough input of information. This study design is not able to eliminate bias, but the size of the cohort is able to partially ameliorate this by potentially reducing sampling error. In the context of a large database study it has the potential to exacerbate aggregation error and errors associated with the systematic exclusion of variables. The large sample size may also add to the significance of some results seen, and some of these 1% – 2% differences may not be seen as clinically important. Additionally, given the constraints of the ACS-NSQIP database, long-term outcomes (Modified Rankin Scale and National Institute of Health Stroke Scale) beyond 30 days cannot be evaluated, which may under report the number of complications. Additionally, analysis was limited to the variables the ACS-NSQIP CEA database provided and was not able to be all encompassing, thus leaving out variables that have been highlighted in other studies, including studies that analyzed the larger ACS-NSQIP database. Furthermore, this database did not include demographic variables, therefore analysis of this was not able to be undertaken. There is a potential for collinearity within this data, but the purpose of the multivariate analysis was to control for this. Despite these limitations, this study represents one of the largest patient cohorts use to evaluate post-operative CEA complications. 5. Conclusion Patients undergoing CEA with pre-operative stroke symptoms or with factors that predispose them to stroke are more likely to suffer from post-operative stroke or stroke-like symptoms in the perioperative time period. Additionally, patients with high-risk anatomic and physiologic factors are at an increased risk of stroke postoperatively. This study further reveals an association between contralateral ICA stenosis and post-operative stroke. Patients with these pre-operative risk factors should be closely monitored for postoperative complications in an effort to improve patient outcomes. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077
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Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2020.01.077.
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Please cite this article as: V. S. Shah, D. Kreatsoulas, D. Dornbos et al., The impact of pre-operative symptoms on carotid endarterectomy Outcomes: Analysis of the ACS-NSQIP carotid endarterectomy database, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.077