Influence of Collateral Circulation and Clamping Duration on Neurological Outcomes in Asymptomatic Patients after Carotid Endarterectomy

Asymptomatic carotid artery stenosis (ACS) refers to stenosis in persons without a history of ischemic stroke, transient ischemic attack, or other neurologic symptoms referable to the carotid arteries [1]. The prevalence of asymptomatic carotid artery stenosis is around 2% in the general population but increases with age [2]. Silent brain infarcts larger than 3 mm were registered in 20–30% of asymptomatic patients [3]. The European Society for Vascular Surgery (ESVS) has recently updated its guidelines on the management of atherosclerotic carotid artery disease, emphasizing the importance of best medical treatment for patients with significant asymptomatic carotid stenosis. The guidelines recommend considering carotid endarterectomy (CEA) or carotid artery stenting for patients with significant stenosis who also present one or more clinical or imaging features indicating a higher risk of future stroke despite BMT [2].

The cerebral arteries on the side of extracranial carotid stenosis experience maximal dilation as a compensatory mechanism to uphold adequate brain perfusion, thereby diminishing the functional reserve of circulation [4]. Prior investigations in individuals with extracranial carotid disease suggest a notable increase in postoperative complications when there is a disruption in the continuity of the anterior or posterior segment of the Circle of Willis (CoW) [5]. Recent studies indicate that the completeness and functionality of the CoW are crucial in determining the risk of ischemic events during carotid interventions. Studies by Czinege et al. and Magyar-Stang et al. have shown that CoW integrity significantly affects cerebrovascular reserve and perioperative risk in carotid artery disease patients [6,7]. Furthermore, data suggest that incomplete CoW configurations are present in over 50% of individuals, with significant variability influencing collateral blood flow capacity [8].

Given the importance of cerebrovascular collateralization in preserving neurological function, evaluating the role of CoW morphology and clamping duration during CEA is essential. This study aims to assess the impact of CoW integrity and duration of carotid clamping on postoperative neurological outcomes in asymptomatic patients undergoing elective CEA. Understanding these factors may contribute to refining patient selection and optimizing surgical techniques to reduce perioperative risks.

This retrospective cohort study enrolled 70 asymptomatic patients between January 2023 and July 2023 who underwent elective carotid endarterectomy (eCEA). Inclusion criteria comprised asymptomatic patients with carotid artery stenosis >70% (including those with unilateral stenosis >70% and contralateral occlusion). Symptomatic patients presenting typical carotid symptoms such as transient ischemic attack (TIA), amaurosis fugax, or a history of stroke were excluded. Anamnestic data on risk factors were collected, including hypertension (diagnosed or under chronic antihypertensive therapy), diabetes (diagnosed or under chronic therapy), hyperlipoproteinemia (LDL cholesterol >3.5 mmol/L, total cholesterol >5.2 mmol/L, or chronic hypolipemic therapy), smoking history within the past two years, and diagnosed heart diseases based on cardiologist findings. Variables included the presence of coronary disease, angina pectoris, previous myocardial infarction, myocardial revascularization, left ventricular hypertrophy, heart rhythm disorders, and peripheral arterial disease. Additionally, 8 patients had simultaneous coronary artery bypass grafting (CABG) performed with eCEA due to extensive coronary artery disease. The decision for simultaneous operation was reached by Heart and Vascular Team.

The decision for eCEA was made following duplex ultra-sonography and multidetector computed tomography (MDCT) angiography, with carotid stenosis assessed based on established criteria. Patients were categorised into two groups based on CoW morphology: those with complete CoW and those with incomplete CoW, characterized by anterior segment disruption (ACA1, AcomA), ipsilateral posterior collateral segment disruption (ACP1, AcomP), hypoplasia of both anterior and posterior collateral segments on the side of significant carotid stenosis, or the presence of foetal ACP.

All patients underwent eCEA under general anaesthesia, utilizing the eversion technique. Intraoperatively, the duration of carotid artery clamping was recorded for each patient. Postoperatively, patients were closely monitored by a neurologist and discharged home after an average of 3 days in the absence of complications. Primary outcomes included post-operative stroke, TIA, and neurological mortality.

The research has been conducted in full compliance with the Helsinki Declaration on ethical conduct and in accordance with the principles of Good Clinical Practice (GCP), national regulations and institutional policies and has been approved by the authors' institutional Ethics committee (No29/22).

Risk factors in the group of patients with and without insufficiency of the ring of Willis are given in Table 1. There was no statistically significant difference in age between patients with complete and incomplete CoW (p>0.05). There is a significant difference in the frequency of CoW insufficiency in men compared to women (p=0.004). Twenty patients (28.6%) reported vertigo on admission. There is a statistically significant difference in the frequency of vertebrobasilar basin insufficiency in these patients compared to those without vertigo symptoms (p<0.05).

Postoperative neurological complications were recorded in 2 patients (2.9%). Both had ischemic stroke. None of the examined risk factors was associated with the occurrence of postoperative neurological complications in asymptomatic patients (Table 2). All patients with postoperative neurological complications had a preserved polygon of Willis.

The average duration of the clamp was 20 minutes (range 9–30 minutes). There is a statistically significant difference in the duration of the clamp in patients with postoperative neurological complications compared to patients without complications (p=0.034). In univariate logistic regression analysis, the length of clamping proved to be a significant predictor of neurological complications (OR: 1.191; 95% CI: 0.999–1.419; p=0.049).

In 8 (11.4%) patients, CABG was performed simultaneously with the operative treatment of carotid disease. No postoperative neurological complication was recorded in this group of patients.

In-hospital mortality was recorded in one patient (1.4%) who died as a result of stroke. In this patient, CoW inefficiency was not described, and the clamp lasted 30 minutes.

The average length of hospitalization was 5 days (range 4–92 days). Length of hospitalization was not significantly different in patients with and without neurological complications. Hospitalization was significantly longer in patients who underwent myocardial revascularization in addition to carotid surgery (22 vs 4.5 days; p<0.001).

While prior research has emphasized anatomical variations in the CoW, our findings suggest that functional insufficiency-the inability of existing collaterals to compensate for hypoperfusion-is a more critical determinant of perioperative risk. Patients with an incomplete CoW do not necessarily experience neurological deficits if functional collateral flow is adequate.

The CoW serves as the primary source of contralateral blood supply in patients who undergo carotid artery cross-clamping (CC) for CEA. Its anatomical variations influence outcomes, with fully developed collaterals present in 35–50% of the population. [9,10]. In these individuals, hemodynamic disturbances are minimal, reducing the risk of neurological deficits [11]. However, collateral remodelling in response to carotid stenosis suggests that many CEA candidates have adapted over time, preventing preoperative neurological deficits.

Incomplete CoW has been linked to watershed infarcts and ischemic lesions, with anterior collateral disruption considered an independent risk factor for cerebral ischemia [12,13,14]. According to some authors, the interruption of continuity in the anterior collateralization represents an isolated risk factor for the occurrence of cerebral ischemia even without the presence of extracranial carotid disease [12,15,16]. These results led to the hypothesis that asymptomatic patients with incomplete CoW have an increased risk of developing a neurological deficit, and that such patients would benefit the most from surgical treatment. Surgical treatment performed in asymptomatic patients represents primary prevention before the onset of neurological deficit [2,17]. On the other hand, in the same patients due to incomplete CoW, there is an assumption that there will be a higher risk of perioperative neurological complications. Prior studies report an 87.3% frequency of incomplete CoW in symptomatic patients, with Göksu et al. noting a 72.6% prevalence in those with atherosclerotic carotid disease [18]. The study by Myrcha et al. examined the role of cerebral collateral circulation, particularly the CoW, in carotid artery cross-clamping tolerance during CEA [9]. Their findings showed that contralateral carotid stenosis >70% or occlusion significantly increased the risk of intraoperative neurological deficits (p<0.001), while an incomplete CoW alone was not a predictor. However, data were insufficient to assess its impact on early postoperative outcomes. Similarly, Banga et al. observed a tenfold increase in neurological risk with incomplete anterior or posterior collateralization during CEA without shunting, reinforcing the importance of routine shunt placement in high-risk patients [19]. Conversely, evidence suggests that CEA significantly improves functional reserve and normalizes cerebrovascular reactivity in both asymptomatic and symptomatic patients.

In high-volume institutions, performing more than 150 carotid surgeries annually, perioperative complications in asymptomatic patients are rare, occurring in less than 2% of cases [20]. Our sample did not record any instances of reversible cranial nerve damage, indicating an adequate surgical approach.

Hyperperfusion syndrome was observed in one patient who fully recovered and was discharged for home treatment. The reported incidence of cerebral hyperperfusion after CEA is about 20% [21]. Previous analyses have shown that cerebral hyperperfusion is dependent on the completeness of collateralization within the CoW, poorly controlled arterial tension, and the duration of the clamp. There are currently a few papers discussing the use of ischemic postconditioning (IPCT) in the prevention of hyperperfusion syndrome [22,23].

In patients with disruptions in both anterior and posterior collaterals, a selective shunt was required in 80% of operated patients, compared to only 7% in those with at least one collateral pathway [21]. Hendrikse et al. found that collateral diameter decreases post-CEA, indicating a dynamic CoW capable of flow adaptation [24]. While operative treatment enhances circulatory reserve, particularly in patients with incomplete CoW, the extent to which this influences preoperative and postoperative stroke risk remains unclear. This underscores the need to differentiate between anatomical insufficiency and functional collateral compensation, as functional adaptation may mitigate ischemic risk despite an incomplete CoW.

Patients with a complete CoW have greater tolerance to clamping duration and fewer perioperative neurological complications. Our research showed that the prevalence of CoW variation in asymptomatic patients is 51.4%. There is a significant difference in the frequency of CoW insufficiency between men and women, and a significant association between preoperative dizziness and incomplete CoW in the posterior circulation, likely due to VB insufficiency [25,26].

The absence of anatomical variations of the CoW in asymptomatic patients with postoperative neurological complications may be explained by the development of functional collateral flow over time, which compensates for chronic hypoperfusion and keeps these patients asymptomatic despite significant stenosis [27]. This compensatory mechanism may protect them from neurological complications during surgery. In our study, neurological complications were more dependent on clamping duration, supporting recent research that suggests perioperative risk assessment should consider both the anatomy and functionality of the CoW. Other factors such as inadequately regulated hypertension, anaesthesia type, cardiac instability, and comorbidities also influence outcomes.

In our study, neurological complications correlated more with CC duration than CoW anatomy, emphasizing the need for functional assessments beyond anatomical variations. Our low postoperative stroke rate (2.9%) highlights the protective role of CEA, optimized by surgical expertise and techniques such as IPCT. Notably, patients with functional collateral insufficiency preoperatively exhibited improved hemodynamic stability postoperatively, suggesting that CEA enhances cerebrovascular reserve over time.

Half of the patients with asymptomatic extracranial carotid disease exhibit CoW discontinuity, yet operative treatment effectively restores perfusion with a low complication rate. CoW remodelling and functional collateral adaptation likely compensate for hypoperfusion, explaining the lack of association between CoW insufficiency and neurologic complications. Other compensatory mechanisms, including collateral recruitment and autoregulation, further support cerebral circulation. However, extended clamping duration remains a key risk factor, highlighting the need for careful intraoperative management.