Savastano, Luis

Objective To systematically analyse prior reports of carotid endarterectomy (CEA) performed in cases of ≤50% carotid stenosis in order to understand patient tolerance and potential benefit. Methods A systematic review and descriptive analysis was performed in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An English-language search was performed of online databases using librarian-selected search terms. Abstracts were reviewed for relevance which included mention of carotid endarterectomy and stenosis. Prospective or retrospective observational cohort studies that reported series of patients who underwent endarterectomy for minimal (≤50%) luminal stenosis with reported outcomes were included. Results Six studies (which included our institutional series) with a total of 143 patients met the inclusion criteria. The weighted mean age at the time of CEA was 72.3 years; 113 (79.0%) were male. 55.8% of patients with available data had recurrent ipsilateral ischaemic events despite medical therapy. Two patients out of 129 with available perioperative data (1.6%) had perioperative MRI findings of acute ischaemic stroke, both within the hemisphere contralateral to the side of CEA. Of the 138 patients with available follow-up (mean, 36 months), none had recurrent ipsilateral ischaemic events. Conclusions Endarterectomy for symptomatic carotid disease causing ≤50% stenosis may be a potentially beneficial strategy to prevent stroke recurrence. Studies with robust methodology are needed to draw more definitive conclusions in terms of the safety and efficacy of endarterectomy for minimal stenosis with vulnerable features relative to intensive medical therapy.

Background and aim First pass effect (FPE) is defined as achieving a complete recanalization with a single thrombectomy device pass. Although clinically desired, FPE is reached in less than 30% of thrombectomy procedures. Multiple device passes are often necessary to achieve successful or complete recanalization. We performed a systematic review and meta-analysis to determine the recanalization rate after each pass of mechanical thrombectomy and its association with good neurological outcome. Methods A literature search was performed for studies reporting the number of device passes required for either successful (mTICI 2b or higher) or complete (mTICI 2c or higher) recanalization. Using random-effect meta-analysis, we evaluated the likelihood of recanalization and good neurological outcome (measured with the modified Rankin Score <2 at 90 days) after each device pass. Results Thirteen studies comprising 4197 patients were included. Among cases with failed first pass, 24% of them achieved final complete recanalization and 45% of them achieved final successful recanalization. Independently to the total number of previously failed attempts, the likelihood of achieving successful recanalization was 30% per pass, and the likelihood to achieve complete recanalization was about 20% per pass. The likelihood of good neurological outcome in patients with final successful recanalization decreased after each device pass: 55% after the first pass, 48% after the second pass, 42% after the third pass, 36% after the fourth pass, and 26% for 5 passes or more. Conclusion Each pass is associated with a stable likelihood of recanalization but a decreased likelihood of good neurological outcome.

Purpose This study sought to validate whether the signal intensity ratio (SIR) of carotid intraplaque hemorrhage (IPH) was associated with acute ischemic neurologic events. Methods A retrospective review was completed of consecutive patients that underwent neck magnetic resonance angiography using magnetization prepared-rapid gradient echo (MP-RAGE) and T1-CUBE sequences between 2017 and 2020. Patients with magnetic resonance evidence of IPH were included. SIRs were measured by comparing the maximum IPH signal with the mean intramuscular signal from the adjacent sternocleidomastoid. Patients were stratified into ischemic or non-ischemic groups based on the presence of acute ipsilateral ischemic events (stroke, retinal artery occlusion). Logistic regression analysis was performed to determine if increasing IPH SIR was associated with an increased risk of ipsilateral ischemic events. Results Of 85 included patients (85 arteries), 66 were male (77.6%). Mean age was 71.0 (SD ± 11.1). There were 70 arteries with IPH that were ipsilateral to an ischemic event, and 15 that belonged to patients without an ischemic event. No association was found between increasing IPH SIR seen on MP-RAGE (odds ratio (OR): 0.82; 95% confidence interval (CI): 0.58–1.4; P = 0.43) or T1-CUBE sequences (OR: 0.85; 95% CI: 0.53–1.5; P = 0.56). Conclusions There was no association between the SIR of IPH and acute ischemia on either MP-RAGE or T1-CUBE sequences. Further investigation is required prior to widespread acceptance of SIR as a predictive imaging marker of symptomatic carotid plaque.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Background and aim Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

Preclinical testing platforms have been instrumental in the research and development of thrombectomy devices. However, there is no single model which fully captures the complexity of cerebrovascular anatomy, physiology, and the dynamic artery-clot-device interaction. This article provides a critical review of phantoms, in-vivo animal, and human cadaveric models used for thrombectomy testing and provides insights into the strengths and limitations of each platform. Articles published in the past 10 years that reported thrombectomy testing platforms were identified. Characteristics of each test platform, such as intracranial anatomy, artery tortuosity, vessel friction, flow conditions, device-vessel interaction, and visualization, were captured and benchmarked against human cerebral vessels involved in large-vessel occlusion stroke. Thrombectomy phantoms have been constructed from silicone, direct 3D-printed polymers, and glass. These phantoms represent oversimplified patient-specific cerebrovascular geometry but enable adequate visualization of devices and clots under appropriate flow conditions. They do not realistically mimic the artery-clot interaction. For the animal models, arteries from swine, canines, and rabbits have been reported. These models can reasonably replicate the artery-clot-device interaction and have the unique value of evaluating the safety of thrombectomy devices. However, the vasculature geometries are substantially less complex and flow conditions are different from human cerebral arteries. Cadaveric models are the most accurate vascular representations but with limited access and challenges in reproducibility of testing conditions. Multiple test platforms should be likely used for comprehensive evaluation of thrombectomy devices. Interpretation of the testing results should take into consideration platform-specific limitations.

Introduction: Suction catheters and stent retrievers are based on the classical paradigm of “en bloc” removal of emboli by generation of tensile forces by vacuum or device withdrawal. However, in this process emboli elongate and fracture leading to fragmentation. Fragments can migrate downstream or remain impacted in the arterial wall resulting in a residual occlusion. Hypothesis: Clot ingestion is biomechanically superior to “en bloc” removal and leads to higher recanalization rates with less complications. Methods: To test this hypothesis, we present a hybrid test bed consisting of pressurized human brains which was developed and validated for large vessel occlusion (LVO) and revascularization. We fabricated 3 types of representative embolus analogs (EAs) (elastic, fragment-prone and stiff) and recreated 105 LVO in twenty-four fresh human brains with the vasculature connected to an hydraulic system to mimic physiological flow and pressures. Recanalization was attempted in 61 LVO cases by Direct Aspiration (DA) using an 068 catheter and in 44 LVO cases combining Stent Retriever with Aspiration (SR+A). Rates of successful recanalization (SR, Grade 2b or higher) and complete recanalization (CR, Grade 2c or higher) were measured. Up to 4 attempts were done before declaring a failure (Grade 2a or lower). Results: DA resulted in 90% of SR, 79% of CR, 61% of first pass SR and 49% of first pass CR. SR+A resulted in 34% of SR, 34% of CR, 23% of first pass SR and 14% of first pass CR. Elastic EA were associated with 88% of SR, 85% of CR, 61% of first pass SR and 52% of first pass CR. Stiff EAs were associated with 64% of SR, 64% of CR, 36% of first pass SR and 36% of first pass CR. Fragment-prone EAs were associated with 64% of SR, 40% of CR, 38% of first pass SR and 21% of first pass CR. Conclusion: Clot ingestion is biomechanically superior to “en bloc” removal and leads to the highest rates of SR, CR and first pass recanalization. DA achieves higher recanalization rates than SR+A. Elastic clots are associated with the highest rates or recanalization, followed by stiff clots and finally by fragment-prone clots.

Introduction Angio-Seal is a commonly used device for femoral hemostasis in neuroendovascular procedures. This meta-analysis investigates of the safety and efficacy of Angio-Seal in patients undergoing endovascular neurointerventional procedures. Methods A systematic review and meta-analysis on all studies evaluating the Angio-Seal device in neurointerventional procedures from inception through 2020 were performed. We studied rates of groin hematoma, retroperitoneal hematoma, pseudoaneurysm, ipsilateral DVT, and ischemic complications. Meta-analysis was performed using the random-effects model. Results 13 studies were included in our analysis. 2250 patients with 104 complications were found {4.5% (95% CI, 2.7%–6.3%)}. Of these complications, groin hematoma was the most common with a rate of 2.4% (95% CI, 1.1%–3.6%). Retroperitoneal hematoma {0.3% (95% CI, 0%–0.5%)}, pseudo-aneurysm {0.5% (95% CI, 0.2%–0.8%), and ipsilateral DVT {0.3% (95% CI, 0.1%–0.7%) were also not in negligible rate. The rate of other complications were as follows: vessel occlusion/stenosis; 0.2% (95% CI, 0%–0.4%), vascular surgery; 0.2% (95% CI, 0%–0.5%), and infection; 0.2% (95% CI, 0%–0.5%). One patient died as result of hemorrhagic complications {0.1% (95% CI, 0%–0.3%)}. Use of anticoagulant/antiplatelet therapy was found to be positively correlated with high risk of any groin complication and groin hematoma (p ≤ .05). Female gender was associated with high risk of ipsilateral DVT (p ≤ .05). Interestingly, large sheath size was associated with low risk of groin hematoma (p ≤ .05). Conclusion The safety and efficacy rate of Angio-Seal was approximately 95%. The most common complication was groin hematoma. Serious complications including retroperitoneal hematoma and femoral artery occlusion were rare.