Analysis of postprocedural microembolic infarctions and global oxygen extraction fraction during balloon-protected carotid artery stenting: Preliminary study
- Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaski, Kanagawa, Japan.
DOI:10.25259/SNI_919_2020Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Hidemichi Ito, Masashi Uchida, Hiroshi Takasuna, Ichiro Takumi, Tanaka Yuichiro. Analysis of postprocedural microembolic infarctions and global oxygen extraction fraction during balloon-protected carotid artery stenting: Preliminary study. 08-Mar-2021;12:87
How to cite this URL: Hidemichi Ito, Masashi Uchida, Hiroshi Takasuna, Ichiro Takumi, Tanaka Yuichiro. Analysis of postprocedural microembolic infarctions and global oxygen extraction fraction during balloon-protected carotid artery stenting: Preliminary study. 08-Mar-2021;12:87. Available from: https://surgicalneurologyint.com/surgicalint-articles/10636/
Background: Atherosclerotic carotid stenosis with impaired cerebral perfusion is a risk factor for cerebral ischemia. In major carotid stenoocclusive diseases, increased oxygen extraction fraction (OEF) is associated with ischemic stroke. Balloon-protected carotid artery stenting (CAS) is valuable for high-grade carotid stenosis. However, while balloon-protected CAS can effectively reduce the occurrence of ischemic complications by blocking carotid flow, cerebral hypoperfusion may result in simultaneous cerebral ischemia. We sought to evaluate whether increased OEF during balloon-protected CAS can predict postprocedural microembolic infarction (MI).
Methods: Eighty-four patients who underwent balloon-protected CAS were enrolled. Initial, intraprocedural, and postprocedural OEFs were calculated from the cerebral arteriovenous oxygen differences obtained from blood sampled just before the temporary occlusion and reperfusion of the internal carotid artery during and after the procedure. MIs were evaluated by diffusion-weighted imaging (DWI). Patients were classified into two groups based on the presence or absence of new MIs, and the relationship between the OEF and postprocedural MIs was analyzed.
Results: New DWI-positive lesions were found in 37 cases (44.0%). Age, signal intensity ratio (SIR) of carotid plaque on T1-weighted black blood magnetic resonance imaging, and intraprocedural OEF were significantly higher in the DWI-positive group. The high SIR and intraprocedural OEF were significantly associated with the development of postprocedural MIs in multivariate analysis. MIs were correlated with the increase in OEF.
Conclusion: Increased intraprocedural OEF, obtained by blood sampling during balloon-protected CAS, could predict the incidence of postprocedural MIs. Patients with carotid stenosis could be hemodynamically compromised by carotid flow blockage during balloon-protected CAS.
Keywords: Balloon protection, Carotid artery stenting, Diffusion, Oxygen extraction fraction
Embolism from atherosclerotic carotid stenosis is one of the most important causes of ischemic stroke.[
Carotid artery stenting (CAS) is an effective endovascular alternative to carotid endarterectomy (CEA) for the prevention of ischemic stroke in patients with atherosclerotic carotid stenosis. In balloon-protected CAS, while the occurrences of ischemic complications are effectively reduced by blocking the anterograde carotid flow, it may simultaneously lead to cerebral hypoperfusion during the procedure. Thus, in some patients, the OEF is expected to increase to maintain the cerebral metabolic rate of oxygen when the cerebral perfusion pressure is critically reduced.[
We hypothesized that patients hemodynamically compromised by the blockage of the carotid flow during balloon-protected CAS could have increased OEF and, therefore, be at a higher risk of developing new MIs as revealed on postprocedural diffusion-weighted imaging (DWI). The aim of this study was to investigate whether increased OEF obtained by the classic blood sampling method, might be a risk factor for MIs following balloon-protected CAS.
We conducted a retrospective study of patients with symptomatic (stenosis ≥50%, per North American Symptomatic Carotid Endarterectomy Trial [NASCET]) or asymptomatic (stenosis ≥80%, per NASCET) atherosclerotic carotid artery stenosis treated by CAS from April 2014 through March 2020 at our institute.[
Information, including patient characteristics, morphology of the carotid arteries, and procedural data, was obtained from each patient’s medical record. Reduced CBF was defined as a decrease of <80% from the contralateral side. Hemodynamic depression (HD) was defined as a decrease of <90 mmHg in systolic blood pressure and a decrease in the heart rate of <50 bpm. Written informed consent was obtained from all the patients.
OEF by blood sampling
OEFs were calculated, by measuring the amount of oxygen in the affected carotid artery and in the angiographically dominant side jugular bulb, just before the temporary occlusion (initial OEF) and reperfusion of the ICA (intraprocedural OEF) during the procedure and 15 min after the procedure (postprocedural OEF) [
Characteristics of the carotid artery lesion were evaluated on digital subtraction angiography and magnetic resonance imaging (MRI). The degree of stenosis was measured on angiography using the NASCET criteria.[
The patients were premedicated with 100 mg of acetylsalicylic acid and 75 mg of clopidogrel or 200 mg of cilostazol for at least 14 days before the procedure without a loading dose. The procedures were performed with femoral (n = 43, 51.2%) or brachial access (n = 41, 48.8%) under local anesthesia. Systemic heparinization was achieved with target activated clotting times between 300 s and 350 s during the procedure.
A distal balloon (Carotid GuardWire PS; Medtronic, Santa Rosa, CA, USA) with and without proximal balloon protection was used in 9 and 75 cases, respectively. Closed-cell stents (Carotid Wallstent Monorail Endoprosthesis; Boston Scientific Corp., Natick, MA, USA) were used mostly (n = 75, 89.3%), and the open-cell stents (Precise; Cordis Corporation, Miami Lakes, FL, USA) were used for cases of tortuous or calcified lesions (n = 9, 10.7%). After postdilation, routine aspiration of debris was performed. Finally, the balloon protection device was retrieved. After the completion of CAS, heparin was not reversed until its effect disappeared spontaneously. During the procedure, blood pressure, heart rate, and neurological symptoms were closely monitored. Atropine sulfate was prophylactically administered just before predilation in all cases. Patients with periprocedural HD were initially given intravenous fluids. Intravenous vasopressor therapy (e.g., dopamine) was administered in those with persistent hypotension despite intravenous fluids.
Continuous variables are reported as the mean ± standard deviation, and comparisons of these variables between the groups were performed using the Mann–Whitney U or Wilcoxon signed-rank tests. Categorical variables are reported as percentages and were compared using Fisher’s exact probability test. Factors predictive in univariate analysis (P < 0.05) were entered into a backward multivariate logistic regression analysis; P < 0.05 was considered statistically significant. The correlation coefficients (r) > 0.5 were considered statistically significant. All statistical analyses were performed with “EZR (Easy R)” software.[
Of the 84 patients studied, balloon-protected CAS was successfully completed in all the cases with no manifestations of neurologic symptoms, and intraprocedural angiography revealed no evidence of distal embolization in the intracranial circulation. Overall, new MIs as revealed on postprocedural DWIs were observed in 37 patients (44.0%). Among them, 14 (37.8%) patients had accompanied MIs in the contralateral cerebral hemisphere as well. The average number of MIs on DWI was 3.0 (range, 1–7). Most of all the new MIs were small round spots located in the watershed zone. No adverse events, such as major or minor stroke, myocardial infarction, or death, were noted in the periprocedural period.
Baseline characteristics of the patients, morphological findings of the vascular structures, and procedural factors were summarized and compared [
In the morphological factors, the SIR was significantly higher in the DWI-positive group compared to that in the DWI-negative group (1.78 vs. 1.52, respectively, P = 0.003). There were no significant differences with respect to total plaque volume, pre- and post-CAS stenotic rate, and the frequency of the presence of anterior and posterior connections.
In the procedural factors, the mean duration of carotid occlusion and activated clotting time were not significantly different between the two groups. Initial, intraprocedural, and postprocedural OEFs were 36.0 ± 6.7%, 46.2 ± 8.9%, and 38.2 ± 6.7% in the DWI-positive group and 38.1 ± 6.4%, 40.3 ± 7.2%, and 38.4 ± 6.5% in the DWI-negative group, respectively. The intraprocedural OEF and the increase in OEF were significantly higher in the DWI-positive group compared with that in the DWI-negative group (P = 0.005 and < 0.001, respectively). Moreover, in the DWI-positive group, the intraprocedural OEF was significantly higher compared with the initial or postprocedural OEFs [
(a) Correlation between the signal intensity ratio and the number of microembolic infarctions (MIs) on the postprocedural diffusion-weighted images, (b) correlation between the increase in OEF and the number of MIs on the postprocedural diffusion-weighted images. OEF: Oxygen extraction fraction.
Cerebral ischemic events are one of the most frequent complications of CAS. Rates of 32.8–51.0% have been reported for subclinical MIs after protected CAS.[
To investigate cerebral hemodynamics, PET and SPECT are useful for measuring OEF, but it is impractical to use because it is complicated, expensive, and unsuitable for real-time evaluation of cerebral hemodynamics during the procedure. In contrast, blood sampling for OEF calculation is simple and available, although the technique is slightly invasive. Hattori et al. demonstrated that the OEF on PET, using a short inhalation of O–O2, was correlated with the blood sampling OEF in healthy human volunteers.[
In this study, the intraprocedural OEF in the DWI-positive group significantly increased due to the ICA occlusion and showed a significantly high value compared to that of the DWI-negative group. In addition, an increase in OEF statistically correlated with the number of new MIs on postprocedural DWIs. As increased intraprocedural OEF could be considered the result of the metabolic compensation for the reduction of the CBF due to the targeted ICA occlusion, our results suggest that there could be patients hemodynamically compromised by carotid flow blockage during balloon-protected CAS, and they could be at risk for the development of periprocedural cerebral ischemia.
Near-infrared spectroscopy and transcranial Doppler (TCD) are also suitable for real-time monitoring during CAS. Near-infrared spectroscopy in CAS has a significant advantage in the measurement of cerebral hemodynamics, which is ease of use. Placement of the sensor on the forehead is fast and easy, and real-time data reflecting changes in cerebrovascular hemoglobin saturation appear immediately. However, the major disadvantage of regional oxygen saturation is that it can measure only a small, limited area of the frontal cortex.[
HD could also lead to a temporary reduction in cerebral perfusion and contribute to postprocedural cerebral ischemia.[
The association between advanced age and the risk of ischemic events after CAS compared with CEA has been reported in many multicenter randomized controlled trials.[
The characteristics of the carotid lesions, including the degree of stenosis, volume, and vulnerability, were reported to be the most important risk factors of postprocedural MIs after CAS.[
There are several limitations in this preliminary study. First, this study was a retrospective nonrandomized study with a small number of cases. Second, we could not examine platelet aggregation in all the patients using the VerifyNow system (Accumetrics Inc., San Diego, CA, USA). Poor response to antiplatelet drugs could be a risk factor for postprocedural MIs. Third, this method could determine the OEF of the global cerebrum but could not definitively indicate the localization. At present, this method is not accepted as a replacement for PET or SPECT in evaluating cerebral hemodynamics. However, it may prove useful in the real-time evaluation of intraprocedural cerebral hemodynamics during balloon-protected CAS.
Increased intraprocedural OEF during balloon-protected CAS, obtained by the blood sampling method, was associated with an increased incidence of new MIs and correlated with the number of new MIs on postprocedural DWI. This suggests that patients hemodynamically compromised by the blockage of carotid flow during balloon-protected CAS could be at risk for the development of periprocedural cerebral ischemia.
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