[Functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Vazhnost' dinamicheskoi funktsional'noi otsenki patologicheskoi izvitosti vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom.

The review is devoted to diagnosis and treatment of internal carotid artery tortuosity. The authors consider modern classification, epidemiology and diagnostic options using neuroimaging or ultrasound-assisted functional stress tests depending on medical history and complaints. In addition to standard Doppler ultrasound, rotational and orthostatic tests are advisable due to possible changes of local shape and hemodynamic parameters following body position changes, especially in patients with concomitant atherosclerotic stenosis. Thus, a personalized approach is especially important for treatment and diagnostics of internal carotid artery tortuosity.

[Dynamic functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Dinamicheskaya funktsional'naya otsenka patologicheskikh izvitostei vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom. Klinicheskii sluchai.

A personalized approach with attention to anamnesis and specific symptoms is necessary in patients with internal carotid artery tortuosity. Neuroimaging (especially before elective surgery) or functional stress tests following ultrasound of supra-aortic vessels may be necessary depending on medical history and complaints. In addition to standard Doppler ultrasound, these patients should undergo rotational and orthostatic transformation tests. We analyze changes in shape and hemodynamic parameters within the tortuosity area in various body positions. This is especially valuable for patients with concomitant carotid artery stenosis. The article presents a clinical case illustrating the importance of such approach.

Alternative Splicing of FN (Fibronectin) Regulates the Composition of the Arterial Wall Under Low Flow.

OBJECTIVE: Exposure of the arterial endothelium to low and disturbed flow is a risk factor for the erosion and rupture of atherosclerotic plaques and aneurysms. Circulating and locally produced proteins are known to contribute to an altered composition of the extracellular matrix at the site of lesions, and to contribute to inflammatory processes within the lesions. We have previously shown that alternative splicing of FN (fibronectin) protects against flow-induced hemorrhage. However, the impact of alternative splicing of FN on extracellular matrix composition remains unknown. Approach and Results: Here, we perform quantitative proteomic analysis of the matrisome of murine carotid arteries in mice deficient in the production of FN splice isoforms containing alternative exons EIIIA and EIIIB (FN-EIIIAB null) after exposure to low and disturbed flow in vivo. We also examine serum-derived and endothelial-cell contributions to the matrisome in a simplified in vitro system. We found flow-induced differences in the carotid artery matrisome that were impaired in FN-EIIIAB null mice. One of the most interesting differences was reduced recruitment of FBLN1 (fibulin-1), abundant in blood and not locally produced in the intima. This defect was validated in our in vitro assay, where FBLN1 recruitment from serum was impaired by the absence of these alternatively spliced segments. CONCLUSIONS: Our results reveal the extent of the dynamic alterations in the matrisome in the acute response to low and disturbed flow and show how changes in the splicing of FN, a common response in vascular inflammation and remodeling, can affect matrix composition.

Risk Factors for and Intraoperative Management of Intolerance to Flow Reversal in TCAR.

BACKGROUND: In patients deemed high risk for carotid endarterectomy (CEA) who are indicated for treatment of carotid artery stenosis (CAS), transcarotid artery revascularization (TCAR) has been demonstrated as a safe and effective alternative to trans-femoral carotid artery stenting (TF-CAS). Compared to CEA, where approx. 12% of patients undergoing awake intervention do not tolerate internal carotid artery (ICA) clamping, only 1-2% of patients were observed to have intolerance to flow reversal during TCAR based on data from the ROADSTER1/2 trials. This study reviewed awake interventions from those trials to assess factors associated with intolerance to flow reversal and review how those cases were managed. METHODS: This is a retrospective review of prospectively collected data from Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial along with the subsequent post-approval (ROADSTER-2) trial. The subset of patients from both trials undergoing awake TCAR was analyzed to compare demographics, procedural details, and anatomic factors between patients who did and did not experience intolerance to reversal of flow to assess for predisposing factors. Patients were deemed intolerant to flow reversal at the discretion of the operator, often related to changes in completion of neurologic tasks, hemodynamic stability, or patient reported symptoms. RESULTS: A total of 103 patients from ROADSTER and 194 patients from ROADSTER-2 underwent TCAR under local/regional anesthesia. Of these, 8 patients had intolerance to flow reversal, though all cases were successfully completed. While intraoperative hemodynamic data was only available for 5 of the 8 intolerant patients, none experienced hypotension. 4 cases were completed under low flow reversal, 3 cases were successfully weaned from low to high flow over several minutes, and 1 case required general anesthesia. No significant association was found between intolerance to flow reversal and comorbidities including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), congestive heart failure (CHF), prior MI or angina, pre-op CAS-related symptoms, prior stroke, prior CAS or CEA, prior neck radiation, tandem stenosis, high cervical stenosis, or hostile neck. A trend towards significance was seen with chronic obstructive pulmonary disease (COPD) and contralateral carotid artery occlusion (P = 0.086 and 0.139, respectively). CONCLUSIONS: Despite intolerance to flow reversal, TCAR cases were successfully completed by adjusting reversal-of-flow rate and do not typically require conversion to GETA. While factors contributing to intolerance of flow reversal during TCAR remain poorly understood, this study identified a trend towards significance with an association of preexisting COPD and contralateral carotid artery occlusion. Given the low number of patients who experienced this issue, a larger sample size is required to better elucidate these trends.

Modifications in Near Infrared Spectroscopy for Cerebral Monitoring During Carotid Endarterectomy in Asymptomatic and Symptomatic Patients.

BACKGROUND: To evaluate trends and differences in Near Infrared Spectroscopy (NIRS) monitoring during carotid endarterectomy (CEA) in patients affected by asymptomatic and symptomatic carotid artery stenosis, to predict postoperative neurological complications (PNCs). METHODS: NIRS data of CEAs performed in a University Hospital were retrospectively reviewed. All the interventions were performed under general anesthesia and patients with intraoperative complications were excluded. Mean regional Oxygen Saturation Index (rSO2), pre-clamp values (mean baseline value, MBv and Single Mark Baseline value, SMBv) were collected and compared to the lowest rSO2 values during carotid cross-clamp (LSO2v) calculated within 3 min (percentage drop, PD). ROC curve analysis with Youden's Test was performed to determine the best threshold value of PD, in order to identify PNCs in both asymptomatic and symptomatic groups. RESULTS: Between 2007 and 2015, a total of 399 CEAs were consecutively performed with NIRS monitoring. Three-hundred-seventy-two CEAs in 355 patients were reviewed. Asymptomatic stenoses were 291 (81.9%), eleven (2.9%) PNC were registered (5 in asymptomatic and 6 in symptomatic group). Asymptomatic and symptomatic diseases had different MBv (69.5 ± 7.5 vs. 71.8 ± 6.9, respectively; P = 0.011) and similar rSO2 value during carotid clamping (63.7 ± 8.0 vs. 63.7 ± 6.7, respectively: P = 0.958). Asymptomatic patients experiencing PNCs had a greater PD than non-PNCs group (20.5 ± 10.2% vs. 12.5 ± 7.6%, respectively using MBv as baseline value; P = 0.002), in contrast, in symptomatic patients, in which a low PD was associated with PNCs, it does not reach statistical significance (using MBv, 12.6 ± 5.4% vs. 14.8 ± 6.7%, respectively; P= 0.476). In order to detect PNCs, ROC analysis revealed an optimal PD cut-off value of -17% in asymptomatic CEAs. (Sensibility (Se) 0.80, Specificity (Sp) 0.76, PPV 0.05, NPV 0.99, Youden's index 0.56; P = 0.020) In symptomatic a threshold value of -9% was found, without reaching statistical significance. CONCLUSIONS: NIRS as cerebral monitoring during CEA can predict PNCs in asymptomatic stenosis. Asymptomatic and symptomatic groups differ in baseline and intraprocedural cut-off values to detect an augmented PNCs risk.

Increased Ipsilateral Posterior Cerebral Artery P2-Segment Flow Velocity Predicts Hemodynamic Impairment.

BACKGROUND AND PURPOSE: Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined. METHODS: Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined. RESULTS: The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; R2=0.61), which remained unchanged when evaluating the follow-up data. Using a PCA-P2 systolic flow velocity cutoff value of 85 cm/second, patients with BOLD-CVR based hemodynamic failure stage 2 were diagnosed with an area under the curve of 95. CONCLUSIONS: In patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.

Establishing a carotid artery stenosis disease cohort for comparative effectiveness research using natural language processing.

OBJECTIVE: Investigation of asymptomatic carotid stenosis treatment is hindered by the lack of a contemporary population-based disease cohort. We describe the use of natural language processing (NLP) to identify stenosis in patients undergoing carotid imaging. METHODS: Adult patients with carotid imaging between 2008 and 2012 in a large integrated health care system were identified and followed through 2017. An NLP process was developed to characterize carotid stenosis according to the Society of Radiologists in Ultrasound (for ultrasounds) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) (for axial imaging) guidelines. The resulting algorithm assessed text descriptors to categorize normal/non-hemodynamically significant stenosis, moderate or severe stenosis as well as occlusion in both carotid ultrasound (US) and axial imaging (computed tomography and magnetic resonance angiography [CTA/MRA]). For US reports, internal carotid artery systolic and diastolic velocities and velocity ratios were assessed and matched for laterality to supplement accuracy. To validate the NLP algorithm, positive predictive value (PPV or precision) and sensitivity (recall) were calculated from simple random samples from the population of all imaging studies. Lastly, all non-normal studies were manually reviewed for confirmation for prevalence estimates and disease cohort assembly. RESULTS: A total of 95,896 qualifying index studies (76,276 US and 19,620 CTA/MRA) were identified among 94,822 patients including 1059 patients who underwent multiple studies on the same day. For studies of normal/non-hemodynamically significant stenosis arteries, the NLP algorithm showed excellent performance with a PPV of 99% for US and 96.5% for CTA/MRA. PPV/sensitivity to identify a non-normal artery with correct laterality in the CTA/MRA and US samples were 76.9% (95% confidence interval [CI], 74.1%-79.5%)/93.1% (95% CI, 91.1%-94.8%) and 74.7% (95% CI, 69.3%-79.5%)/94% (95% CI, 90.2%-96.7%), respectively. Regarding cohort assembly, 15,522 patients were identified with diseased carotid artery, including 2674 exhibiting equal bilateral disease. This resulted in a laterality-specific cohort with 12,828 moderate, 5283 severe, and 1895 occluded arteries and 326 diseased arteries with unknown stenosis. During follow-up, 30.1% of these patients underwent 61,107 additional studies. CONCLUSIONS: Use of NLP to detect carotid stenosis or occlusion can result in accurate exclusion of normal/non-hemodynamically significant stenosis disease states with more moderate precision with lesion identification, which can substantially reduce the need for manual review. The resulting cohort allows for efficient research and holds promise for similar reporting in other vascular diseases.

Cardiac output and cerebral blood flow during carotid surgery in regional versus general anesthesia: A prospective randomized controlled study.

OBJECTIVE: Carotid endarterectomy (CEA) is a preventive procedure aimed at decreasing the subsequent risk of fatal or disabling stroke in patients with significant carotid stenosis. It is well-known that carotid surgery under ultrasound-guided regional anesthesia (US-RA) causes a significant increase in blood pressure, heart rate and stress hormone levels owing to increased sympathetic activity. However, little is known about the effects on cardiac output (CO), cardiac index (CI), and cerebral blood flow (CBF) under US-RA as compared with general anesthesia (GA). METHODS: Patients scheduled for CEA were randomized prospectively to receive US-RA (n = 37) or GA (n = 41). The primary end point was the change in CI after induction of anesthesia and the change from baseline over time at four different times during the entire procedure in the respective randomized US-RA and GA groups. In addition to systolic blood pressure and heart rate, we also recorded peak systolic velocity, end-diastolic velocity, and minimum diastolic velocity as seen from transcranial Doppler ultrasound examination, as well as regional cerebral oxygenation (rSO2) as seen from near-infrared refracted spectroscopy to evaluate cerebral blood flow. RESULTS: In the US-RA group, the CI increased after induction of anesthesia (3.7 ± 0.8 L/min/m2) and remained constant until the end of the procedure. In the GA group CI was significantly lower (2.4 ± 0.6 L/min/m2; P < .001). After induction of anesthesia, the rSO2 remained constant in the GA group on both the ipsilateral (63 ± 9 rSO2) and the contralateral (65 ± 7 rSO2) sides; in contrast, it significantly increased in the US-RA group (ipsilateral 72 ± 8 rSO2; P < .001; contralateral 72 ± 6 rSO2; P < .001). The transcranial Doppler ultrasound parameters (peak systolic velocity, end-diastolic velocity, and minimum diastolic velocity) did not differ between the US-RA and the GA group. The clinical outcome was similarly favorable for both groups. CONCLUSIONS: CI was maintained near baseline values throughout the procedure during US-RA, whereas a significant decrease in CI values was observed during CEA under GA. Near-infrared refracted spectroscopy values, reflecting blood flow in small vessels, were higher in US-RA patients than in those with GA. These differences did not influence clinical outcome.

Meta-analysis of redo stenting versus endarterectomy for in-stent stenosis after carotid artery stenting.

OBJECTIVE: The development of in-stent restenosis (ISR) hinders the long-term patency of carotid artery stenting (CAS), yet no optimal treatment has been established. In the present study, we compared the outcomes of redo CAS (rCAS) and carotid endarterectomy (CEA) for ISR. METHODS: A systematic search using the terms "in-stent restenosis," "carotid endarterectomy," and "carotid artery stenting" was conducted in the PubMed, Embase, and Cochrane databases. Studies reporting perioperative stroke, death, and other important complications of rCAS or CEA for ISR after previous CAS with four or more patients were included. Pooled and sensitivity analyses were conducted to synthesize and compare estimates of the outcomes. RESULTS: A total of 11 studies with 1057 patients who had undergone rCAS (n = 894) or CEA (n = 163) met the inclusion criteria. The CEA group had a significantly greater proportion of symptomatic patients (rCAS vs CEA, 30.4% vs 42.1%; P < .01). The duration from primary CAS to reintervention was relatively longer in the CEA group (rCAS vs CEA, median, 8.8 months [range, 3-26 months] vs 19.9 months [range, 0-54 months]). In the rCAS group, a greater proportion of patients had hypertension, hypercholesterolemia, and coronary artery disease and had received antiplatelet therapy before reintervention. Because of insufficient data or a low incidence, the only complications feasible for further analysis were restenosis, myocardial infarction, cranial nerve injury, and neck hematoma. No significant differences were found in the primary end point of mortality/stroke event-free rate (rCAS vs CEA, 99% vs 98%; P > .05) or other secondary end points (event-free restenosis, 100% vs 100%; event-free myocardial infarction, 100% vs 98%; event-free cranial nerve injury, 100% vs 98%; event-free neck hematoma, 100% vs 100% for rCAS vs CEA; P > .05 for all). CONCLUSIONS: rCAS is commonly used to treat patients with severe and/or symptomatic ISR after primary CAS. Although the endovascular approach is less invasive, both rCAS and CEA can be performed safely with similar short- and midterm outcomes of stroke, death, and surgery-related complications.

Revascularization for asymptomatic carotid artery stenosis improves balance and mobility.

OBJECTIVE: Balance and mobility function worsen with age, more so for those with underlying chronic diseases. We recently found that asymptomatic carotid artery stenosis (ACAS) restricts blood flow to the brain and might also contribute to balance and mobility impairment. In the present study, we tested the hypothesis that ACAS is a modifiable risk factor for balance and mobility impairment. Our goal was to assess the effect of restoring blood flow to the brain by carotid revascularization on the balance and mobility of patients with high-grade ACAS (≥70% diameter-reducing stenosis). METHODS: Twenty adults (age, 67.0 ± 9.4 years) undergoing carotid endarterectomy for high-grade stenosis were enrolled. Balance and mobility assessments were performed before and 6 weeks after revascularization. These included the Short Physical Performance Battery, the Berg Balance Scale, the Four Square Step Test, the Dynamic Gait Index (DGI), the Timed Up and Go test, gait speed, the Mini-Balance Evaluation Systems Test (Mini-BESTest), and the Walking While Talking complex test. RESULTS: Consistent with our previous findings, patients demonstrated reduced scores on the Short Physical Performance Battery, Berg Balance Scale, DGI, and Timed Up and Go test and in gait speed. Depending on the outcome measure, 25% to 90% of the patients had scored in the impaired range at baseline. After surgery, significant improvements were observed in the outcome measures that combined walking with dynamic movements, including the DGI (P = .02) and Mini-BESTest (P = .002). The proportion of patients with Mini-BESTest scores indicating a high fall risk had decreased significantly from 90% (n = 18) at baseline to 40% (n = 8) after surgery (P = .02). We used Pearson's correlations to examine the relationship between balance and mobility before surgery and the change after surgery. Patients with lower baseline DGI and Mini-BESTest scores demonstrated the most improvement after surgery (r = -0.59, P = .006; and r = -0.70, P = .001, respectively). CONCLUSIONS: Carotid revascularization improved patients' balance and mobility, especially for measures that combine walking and dynamic movements. The greatest improvements were observed for the patients who had been most impaired at baseline.

Quantification and mapping of cerebral hemodynamics before and after carotid endarterectomy, using four-dimensional flow magnetic resonance imaging.

BACKGROUND: Carotid stenosis can profoundly affect cerebral hemodynamics, which cannot simply be inferred from the degree of stenosis. We quantified and mapped the distribution of the blood flow rate (BFR) in the cerebral arteries before and after carotid endarterectomy using four-dimensional (4D) phase-contrast (PC) magnetic resonance imaging (MRI). METHODS: Nineteen patients (age, 71 ± 6 years; 2 women) with symptomatic carotid stenosis (≥50%) undergoing carotid endarterectomy (CEA) were investigated using 4D PC-MRI before and after surgery. The BFR was measured in 17 cerebral arteries and the ophthalmic arteries. Collateral recruitment through the anterior and posterior communicating arteries, ophthalmic arteries, and leptomeningeal arteries was quantified. BFR laterality was significantly different between the paired contralateral and ipsilateral arteries. Subgroups were defined according to the presence of collateral recruitment. RESULTS: The total cerebral blood flow had increased by 15% (P < .01) after CEA. Before CEA, laterality was seen in the internal carotid artery, anterior cerebral artery, and middle cerebral artery (MCA). On the ipsilateral side, an increased BFR was found after CEA in the internal carotid artery (246 ± 62 mL/min vs 135 ± 80 mL/min; P < .001), anterior cerebral artery (87 ± mL/min vs 38 ± 58 mL/min; P < .01), and MCA (149 ± 43 mL/min vs 119 ± 34 mL/min; P < .01), resulting in a postoperative BFR distribution without signs of laterality. In the nine patients with preoperatively recruited collaterals, BFR laterality was found in the MCA before, but not after, CEA (P < .01). This laterality was not found in the 10 patients without collateral recruitment (P = .2). The degree of stenosis did not differ between the groups with and without collateral recruitment (P = .85). CONCLUSIONS: Using 4D PC-MRI, we have presented a comprehensive and noninvasive method to evaluate the cerebral hemodynamics due to carotid stenosis before and after CEA. MCA laterality, seen in the patients with collateral recruitment before CEA, pointed toward a hemodynamic disturbance in MCA territory for those patients. This methodologic advancement provides an insight into the pathophysiology of cerebral hemodynamics in patients with carotid stenosis.

Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion.

OBJECTIVE: We have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV). METHODS: Structural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients. RESULTS: Of the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively). CONCLUSIONS: Interhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.

Dynamic carotid plaque imaging using ultrasonography.

OBJECTIVE: Dynamic image analysis of carotid plaques has demonstrated that during systole and early diastole, all plaque components will move in the same direction (concordant motion) in some plaques. However, in others, different parts of the plaque will move in different directions (discordant motion). The aim of our study was (1) to determine the prevalence of discordant motion in symptomatic and asymptomatic plaques, (2) to develop a measurement of the severity of discordant motion, and (3) to determine the correlation between the severity of discordant motion and symptom prevalence. METHODS: A total of 200 patients with 204 plaques resulting in 50% to 99% stenosis (112 asymptomatic and 92 symptomatic plaques) had video recordings available of the plaque motion during 10 cardiac cycles. Video tracking was performed using Farneback's method, which relies on frame comparisons. In our study, these were performed at 0.1-second intervals. The maximum angular spread (MAS) of the motion vectors at 10-pixel intervals in the plaque area was measured in degrees. Plaques were classified as concordant (MAS, <70°), moderately discordant (MAS, 70°-120°), and discordant (MAS, >120°). RESULTS: Motion was discordant in 89.1% of the symptomatic plaques but only in 17.9% of asymptomatic plaques (P < .001). The prevalence of symptoms increased with increasing MAS. For a MAS >120°, the hazard ratio for the presence of symptoms was 47.7 (95% confidence interval, 18.1-125.6) compared with the rest of the plaques after adjustment for the degree of stenosis and mean pixel motion. The area under the receiver operating characteristic curve for the prediction of the presence of symptoms using the MAS was 0.876 (95% confidence interval, 0.823-0.929). The use of the median MAS (120°) as a cutoff point classified 86% of the plaques correctly (sensitivity, 81.4%; specificity, 91.2%; positive predictive value, 90.2%; and negative predictive value, 83.0%). CONCLUSIONS: The use of the MAS value to identify asymptomatic plaques at increased risk of developing symptoms and, in particular, stroke should be tested in prospective studies.

Intraoperative electroencephalographic changes during transcarotid artery revascularization are more frequent than previously reported.

OBJECTIVE: Up to 14% of patients undergoing carotid endarterectomy with continuous electroencephalographic (EEG) neuromonitoring will require shunt placement because of EEG changes. However, the initial studies of transcarotid artery revascularization (TCAR) found only one patient with temporary EEG changes. We report our experience with intraoperative EEG monitoring during TCAR. METHODS: We conducted a retrospective review of patients who underwent TCAR at two urban hospitals within an integrated healthcare network from May 2017 to January 2020. The data included demographic information, patient comorbidities, symptom status, previous carotid interventions, anatomic details, contralateral disease, intraoperative vital signs and EEG changes, and postoperative major adverse events (transient ischemic attack, stroke, myocardial infarction [MI], and death) both initially and at 30 days postoperatively. The Fisher exact test was used for categorical data and the Wilcoxon rank sum test for continuous data. RESULTS: A total of 89 patients underwent TCAR during the study period, of whom 71 (79.8%) received intraoperative EEG neuromonitoring. Of the 89 patients, 70.8% were men and 29.2% were women. The median age was 75 years (IQR, 68-82.5 years). Symptomatic patients accounted for 41.6% of the cohort. Of the 71 patients who received continuous neuromonitoring, 9 experienced EEG changes during TCAR (12.7%). The changes resolved in seven patients with pressure augmentation in three and switching to a low flow toggle in three. One patient who had sustained EEG changes had a new postoperative neurologic deficit. The median carotid stenosis percentage on preoperative computed tomography angiography was lower for patients with EEG changes than for those without (67% vs 80%; P = .01). No correlation was found between symptom status or 30-day stroke in patients with and without EEG changes (P = .49 and P = .24, respectively). Overall, three postoperative strokes, two postoperative deaths, and one MI occurred, for a composite 30-day stroke, death, and MI rate of 6.7%. CONCLUSIONS: Changes in continuous EEG monitoring were more frequent in our study than previously reported. Less severe carotid stenosis might be associated with a greater incidence of EEG changes. Limited data are available on the prognostic ability of EEG to detect clinically relevant changes during TCAR, and further studies are warranted.

Carotid artery duplex velocity criteria might be equivocal after left ventricular assist device implantation.

BACKGROUND: Although conventional angiography remains the reference standard for the grading of carotid stenosis, carotid duplex ultrasound (CDUS) is the most commonly used modality for determining the degree of carotid stenosis. The validity of CDUS findings for patients after left ventricular assist device (LVAD) implantation is questionable, because the velocities are often altered secondary to the continuous flow nature of the devices. METHODS: A retrospective review was performed of all patients who had undergone LVAD implantation from January 2007 to December 2019. All patients who had undergone CDUS before and after LVAD implantation were included. Patients receiving extracorporeal membrane oxygenation, those with unusable carotid imaging studies, and those with internal carotid artery (ICA) occlusion were excluded. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the ICA and common carotid artery (CCA) and the ICA/CCA ratios were compared before and after LVAD implantation. RESULTS: A total of 36 patients (mean age 59 years; 30 men; 6 women) had undergone CDUS both before and after LVAD implantation (mean, 647 days between imaging studies). A total of 61 ICAs had met the criteria for inclusion. Before LVAD, 7 carotid arteries (13%) had had >50% carotid stenosis and 53 (87%) had had 0% to 50% stenosis. The mean changes in the velocities after LVAD were as follows. The ICA PSV had decreased by 6.12 ± 4.34 cm/s, and the ICA EDV had increased by 13.44 ± 4.23 cm/s. The CCA PSV had decreased by 17.22 ± 4.95 cm/s, and the CCA EDV had increased by 10.83 ± 2.59 cm/s. The mean ICA/CCA ratio had increased by 0.18 ± 0.05. All the mean changes in velocity were significant (P < .01), except for the ICA PSV (P = .167). Among four patients with known stenosis of 60% to 69%, the degree of increase in the ICA and CCA EDVs (75.8 and 13.3 cm/s, respectively) was significantly greater than that for patients with <50% or no stenosis. Carotid artery laterality did not significantly affect the differences in mean velocity. Centrifugal LVADs resulted in a significantly larger increase in the ICA EDV compared with axial LVADs (26.0 vs 6.3 cm/s; P < .01). CONCLUSIONS: LVADs were associated with significant changes in CCA PSV, ICA and CCA EDV, and ICA/CCA ratios. However, the magnitude of these changes in patients with <50% stenosis was minimal and might not be clinically significant. The LVAD type might only have an effect on EDV measurements in the CCA, and the left and right carotid arteries did not appear to have different degrees of change in velocity. The currently used criteria for determining carotid stenosis might result in an under- or overestimation of carotid stenosis in patients with an LVAD.

Primary mechanism of stroke reduction in transcarotid artery revascularization is dynamic flow reversal.

OBJECTIVE: Recent studies have suggested that the low risk of stroke and death associated with transcarotid artery revascularization (TCAR) is partially attributable to a robust dynamic flow reversal system and the avoidance of the atherosclerotic aortic arch during stenting. However, the benefits of flow reversal compared with distal embolic protection (DEP) in reducing stroke or death in TCAR have not been studied. METHODS: All patients undergoing carotid artery stenting (CAS) via the transcarotid route with either dynamic flow reversal (TCAR) or DEP (TCAS-DEP) in the Vascular Quality Initiative from September 2016 to November 2019 were analyzed. Both multivariable logistic regression and nearest neighbor propensity score-matched analysis were performed to explore the differences in outcomes between the two procedures. The primary outcome was in-hospital stroke or death. The secondary outcomes were stroke, death, myocardial infarction (MI), and the composite of stroke, death, and MI. A secondary analysis was performed to compare transcarotid stenting with DEP vs transfemoral CAS with DEP to evaluate the effects of crossing the aortic arch. RESULTS: A total of 8426 patients were identified (TCAS-DEP, n = 287; 3.4%). TCAR was associated with a lower risk of in-hospital stroke or death (1.6% vs 5.2%; odds ratio [OR], 0.35; 95% confidence interval [CI], 0.20-0.64; P = .001), stroke (1.4% vs 4.2%; OR, 0.37; 95% CI, 0.20-0.68; P = .002), and stroke/death/MI (2.0% vs 5.2%; OR, 0.41; 95% CI, 0.23-0.71; P = .001) compared with TCAS-DEP. Among the 274 pairs of patients identified with propensity score matching, TCAR was associated with a lower risk of stroke/death (1.1% vs 4.7%; risk ratio [RR], 0.23; 95% CI, 0.06-0.81; P = .021) and stroke (0.4% vs 4.0%; RR, 0.09; 95% CI, 0.01-0.70; P = .006) compared with TCAS-DEP but no differences in stroke/death/MI (1.8% vs 4.7%; RR, 0.38; 95% CI, 0.15-1.02; P = .077). The secondary analysis found no differences in stroke between TCAS-DEP and transfemoral CAS with DEP (4.9% vs 3.7%; RR, 1.3; 95% CI, 0.36-1.63; P = .65). CONCLUSIONS: Compared with TCAS-DEP, TCAR was associated with a lower risk of perioperative stroke or death and stroke. This finding implies that dynamic flow reversal might provide better neuroprotection than does a distal embolic filter in reducing the perioperative risk of stroke. Avoiding the aortic arch did not confer any reduction in the stroke rate. The present findings serve to separate the clinical benefit of dynamic flow reversal from that of avoiding the aortic arch during TCAR.

Outcomes of transcarotid artery revascularization with dynamic flow reversal in patients with contralateral carotid artery occlusion.

BACKGROUND: The outcomes of carotid revascularization in patients with contralateral carotid artery occlusion (CCO) are controversial. CCO has been defined by the Centers for Medicare and Medicaid Services as a high-risk criterion and is used as an indication for transfemoral carotid artery stenting. With the promising outcomes associated with transcarotid artery revascularization (TCAR), we aimed to study the perioperative outcomes of TCAR in patients with CCO and to assess the feasibility of TCAR in these high-risk patients. METHODS: All patients in the Vascular Quality Initiative database who underwent TCAR with flow reversal between September 2016 and May 2019 were included. Patients with trauma, dissection, or more than two treated lesions were excluded. Univariable and multivariable logistic analyses were used to compare the primary outcome of in-hospital stroke or death after TCAR in patients with CCO and those without CCO (patent and <99% stenosis). Secondary outcomes included intraoperative neurologic changes and the individual outcomes of in-hospital stroke, death, and myocardial infarction as well as 30-day mortality. RESULTS: A total of 5485 TCAR cases were included, of which 593 (10.8%) had CCO. In patients with CCO, mean flow reversal time was shorter (10.1 ± 6.7 minutes vs 11.1 ± 7.8 minutes; P < .01); intraoperative neurologic changes occurred in 1% of these patients compared with 0.7% of those with patent contralateral carotid arteries (P = .43). On univariable analysis, no significant difference in in-hospital stroke or death was shown between patients with and patients without CCO (1.7% vs 1.5%; P = .65). Similarly, no significant differences were noted between the groups in terms of in-hospital death (0.7% vs 0.4%; P = .27), stroke (1.7% vs 1.2%; P = .32), and stroke/death/myocardial infarction (2.2% vs 1.8%; P = .53) as well as 30-day mortality (0.8% vs 0.6%; P = .55). The results remained statistically nonsignificant after adjustment for baseline differences between the groups; the adjusted odds ratio (OR) of in-hospital stroke/death in patients with CCO compared with those with patent contralateral carotid arteries was not significant (OR, 1.39; 95% confidence interval, 0.65-3.0; P = .40). In symptomatic patients presenting with prior stroke, CCO was associated with significantly higher odds of stroke or death (OR, 4.63; 95% confidence interval, 1.39-15.4; P = .01) compared with no CCO. On the other hand, in asymptomatic patients, no significant difference in outcomes was observed between the groups. CONCLUSIONS: In this analysis, TCAR seems to be safe in patients with CCO. Caution should be taken in symptomatic patients with CCO and a history of prior stroke as they might have worse outcomes compared with patients with patent contralateral carotid arteries. Studies with larger sample size and longer follow-up are needed to assess the perioperative and long-term outcomes of TCAR in patients with CCO in comparison to other procedures.

Risk factors and impact of postoperative hypotension after carotid artery stenting in the Vascular Quality Initiative.

OBJECTIVE: Hypotension is a frequent complication of carotid artery stenting (CAS). Although common, its occurrence is unpredictable, and association with adverse events has not been well defined. The aim of this study was to identify predictors of postoperative hypotension after CAS and the association with stroke/transient ischemic attack (TIA), major adverse cardiac events (MACEs), increased length of stay (LOS), and in-hospital mortality. METHODS: This is a retrospective analysis of all CAS procedures, including transfemoral CAS (TF-CAS) and transcarotid artery revascularization (TCAR), performed in the Vascular Quality Initiative between 2003 and 2018. The primary study end point was postoperative hypotension, defined as hypotension treated with continuous infusion of a vasoactive agent for ≥15 minutes. Secondary end points included any postoperative neurologic events (stroke/TIA), MACEs (myocardial infarction, congestive heart failure, and dysrhythmias), prolonged LOS (>1 day), and in-hospital mortality. Patients' demographics predictive of hypotension were determined by multivariable logistic regression, and a risk score was developed for correlation with outcomes. RESULTS: During the time period of study, 24,699 patients underwent CAS; 19,716 (80%) were TF-CAS, 3879 (16%) were TCAR, and 1104 (4%) were not defined. Fifty-six percent were for symptomatic disease, 75% were for a primary atherosclerotic lesion, and 72% were performed under local or regional anesthesia. Postoperative hypotension occurred in 15% of TF-CAS and 14% of TCAR patients (P = .50). Patients with hypotension (vs no hypotension) had higher rates of stroke/TIA (7.3% vs 2.6%; P < .001), MACEs (9.6% vs 2.1%; P < .001), prolonged LOS (65% vs 28%; P < .001), and in-hospital mortality (2.9% vs 0.7%; P < .001). By multivariable analysis, risk factors associated with hypotension included an atherosclerotic (vs restenotic) lesion (odds ratio, 2.2; 95% confidence interval, 2.0-2.4; P < .001), female sex (1.3 [1.2-1.4]; P < .001), positive stress test result (1.3 [1.2-1.4]; P < .001), age 70 to 79 years (1.1 [1.1-1.3]; P < .002), age >80 years (1.2 [1.1-1.4]; P < .001), history of myocardial infarction or angina (1.3 [1.2-1.4]; P < .001), and an urgent (vs elective) procedure (1.1 [1.0-1.2]; P < .01). A history of hypertension was protective (0.9 [0.8-0.9]; P < .02). A normalized risk score for hypotension was created from the multivariable model. Increasing risk scores correlated directly with rates of adverse events, including postoperative stroke/TIA, MACEs, increased LOS, and increased in-hospital mortality. CONCLUSIONS: Hypotension after CAS is associated with adverse neurologic and cardiac events as well as with prolonged LOS and in-hospital mortality. A scoring tool may be valuable in stratifying patients at risk. Interventions aimed at preventing postoperative hypotension may improve outcomes with CAS.

Safety and durability of concomitant carotid endarterectomy with carotid-subclavian bypass grafting.

BACKGROUND: Concomitant carotid endarterectomy (CEA; for severe internal carotid artery stenosis) with carotid-subclavian bypass grafting (CSBG; for proximal common carotid artery or subclavian artery occlusion) is rarely used. Only a few studies have been reported. This report analyzed early and late clinical outcomes of the largest study to date of the combined procedures in our institution. METHODS: Electronic medical records of patients who had concomitant CEA with CSBG during three decades were analyzed. Indications for surgery were arm ischemia, neurologic events, and clinical subclavian steal. Early (30 days) perioperative complications (stroke, death, and others) and late complications (stroke, death) were recorded. Kaplan-Meier analysis was used to estimate late graft/CEA primary patency, freedom from stroke, and stroke-free survival rates. Graft patency was determined clinically and confirmed using duplex ultrasound. Outcomes were compared with previously published data on isolated CSBG by the same group. RESULTS: There were 37 combined procedures analyzed. Mean age was 64 years (range, 45-81 years). Indications for surgery were arm ischemia in 12 (32%), hemispheric transient ischemic attack or stroke in 15 (41%), vertebrobasilar insufficiency in 4 (11%), symptomatic subclavian steal in 10 (27%), and asymptomatic common carotid artery occlusion with severe internal carotid artery stenosis in 6 (16%). The 30-day perioperative (stroke and death) rate was 5.4% (one stroke and one death). Immediate symptom relief was noted in 100%, with 2.7% (transient ischemic attack) symptom recurrence. The crude patency rate of both CEA and CSBG was 92%. At 1 year, 2 years, 3 years, 4 years, and 5 years, respectively, primary patency rates were 100%, 96%, 96%, 96%, and 85%; freedom from stroke rates were 97%, 97%, 97%, 97%, and 97%; and stroke-free survival rates were 94%, 94%, 87%, 82%, and 78%. When these outcomes were compared with the isolated CSBG group alone (28 patients), there was no difference in perioperative stroke (2.7% for concomitant CEA/CSBG vs 0% for isolated CSBG), perioperative death (2.7% vs 2.8%), or late patency rates (92% vs 96%). CONCLUSIONS: Concomitant CEA/CSBG is safe and durable. There was no significant difference in perioperative stroke/death or late patency rates compared with isolated CSBG.

Plaque Longitudinal Heterogeneity in Morphology, Property, and Mechanobiology.

BACKGROUND AND PURPOSE: The hemodynamic environment of an atherosclerotic plaque varies along the longitudinal direction. Investigating the changes in plaque morphology and its biomechanical environment along the longitudinal direction and their correlations will enhance our understanding of plaque progression and arterial remodeling. METHODS: Six male patients with carotid stenosis >70% were recruited. Multisequence high-resolution MRI was performed at the carotid bifurcation. Carotid endarterectomy was performed following MRI, and the plaque tissue was collected for histological and mechanical testing. Patient-specific biomechanical modeling and simulations were conducted to calculate the mechanical stresses (wall shear stress [WSS] and von Mises stress [VMS]). Changes in plaque cross-sectional morphology, WSS, and VMS as well as their correlations were evaluated. RESULTS: Positive correlations were found between % stenosis and % inflammation (MA) (p = 0.019), % lipid area and % MA (p = 0.026), and % calcification area and VMS (p = 0.007). Negative correlations were found between VMS and % stenosis (p = 0.028) and VMS and average WSS (p = 0.034). Moreover, the peak stresses and neovessels were found to be in the shoulder regions. High-stress concentrations were found in the interface regions of the calcification and surrounding tissue, thereby increasing plaque vulnerability. CONCLUSIONS: Correlations between the morphology and stresses suggest that arterial remodeling is a dynamic interaction between mechanical environment and plaque progression resulting in plaque heterogeneity. Our finding indicates that plaque heterogeneity is associated with plaque progression and can be combined with mechanical stresses for identifying high-risk plaques.