Late Stroke Research Articles

Abstract WMP99: Proteomics Study Of Stroke In Young Adults

Introduction: A prior systematic Mendelian randomization screen of 653 circulating proteins in a predominantly older ischemic stroke (IS) population identified a causal role for several established and novel biomarkers for IS and IS subtypes. We contrasted the magnitude of genetically determined levels of 6 of these biomarkers between early- and late-onset IS. Methods: We constructed genetic risk scores (GRS) for these 6 protein biomarkers from previously published GWAS analyses carried out in European populations. Using regression analysis, we evaluated associations of these GRS with IS and IS subtypes in 10,549 early onset (ages 18-59) and 9,272 late onset (ages 60 and older) IS cases and associated controls. The Wald test was used to test for heterogeneity in the odds ratios between the two groups. Results: Of the 6 biomarkers, only genetically determined protein levels of histo-blood group ABO system transferase were more strongly associated with early compared to late onset stroke (p < 0.002). Higher genetically determined levels of F11 and LPA and lower genetically determined levels of MMP12 were associated with both early and late onset IS with no evidence for differential effect sizes, while genetically determined levels of CD40 and SCARA5 showed no association with either early or late onset stroke. In subtype-specific analyses, increasing levels of genetically determined F11 were correlated with increased risk of all strokes in both groups. Higher genetically determined LPA levels were associated with large artery atherosclerotic (LAA) strokes in both groups, while lower genetically determined MMP12 levels were associated with LAA strokes in both groups. Conclusions: Genetically determined histo-blood group ABO system transferase levels are more strongly associated with all strokes in early than in late onset stroke. Genetically determined blood protein levels of F11, LPA, and MMP12 were associated with both early and late onset stroke. Lack of association for CD40 and SCARA5 may be due to a smaller sample size than the initial discovery study.

Clinical Relevance of Computed Tomography Perfusion-Estimated Infarct Volume in Acute Ischemic Stroke Patients within the 6-h Therapeutic Time Window

Introduction: Although the estimated infarct volume on baseline computed tomography perfusion (CTP) can identify patients who are likely to benefit from endovascular thrombectomy (EVT) in late time window strokes, the role of CTP imaging in early time windows has not been established. We assessed the clinical impact of CTP-estimated infarct volume on long-term prognosis after EVT, particularly in patients with early time window stroke. Methods: We retrospectively reviewed patients who underwent pretreatment CTP and EVT for large vessel occlusion in the anterior circulation within 6 h after symptom onset between March 2014 and February 2019. The infarct volume at baseline CTP was estimated using commercially available software (RAPID, iSchemaView, Menlo Park, CA, USA) with a cerebral blood flow threshold <30% of the normal brain. Risk factors for poor outcome after EVT were evaluated, and a receiver operating characteristic (ROC) curve analysis was used to identify CTP-estimated infarct volumes that optimally predicted the development of symptomatic intracranial hemorrhage (sICH) and poor outcomes (modified Rankin Scale [mRS] 3–6) at 90 days. Results: Of 120 patients, successful recanalization was achieved in 89 (74.2%) patients, while 61 (50.8%) showed poor outcomes at 90 days. Among 89 patients with successful recanalization after EVT, age, diabetes, clinical stroke severity, CTP-estimated infarct volume, and sICH development were independently associated with 90-day clinical outcomes. ROC analysis identified infarct volumes of ≥88.5 mL and ≥74 mL as the optimal thresholds for predicting poor outcome and development of sICH, respectively. Patients with large infarct volumes showed poorer outcomes (odds ratio [OR], 7.704; 95% confidence interval [CI], 1.528–38.839) and higher rates of sICH development (OR, 10.857; 95% CI, 1.835–64.235). Among patients with large infarction volumes (≥88.5 mL), the 90-day mRS demonstrated a shift toward better outcomes in patients with successful recanalization. Conclusion: Larger initial infarct volumes are significantly associated with worse clinical outcomes in patients who underwent EVT because of early time window stroke. Furthermore, our study of 6-h data demonstrated that an initial infarction of more than a certain volume might be an independent risk factor for sICH development and poor outcomes even in patients with successful recanalization. However, we still observed benefits of EVT in patients with large ischemic cores. The CTP-estimated infarct volume might be an important prognostic factor after EVT rather than a biomarker predicting treatment effectiveness.

Low Incidence of Late Ipsilateral Ischaemic Stroke After Treatment for Symptomatic Carotid Stenosis in Sweden 2008–2017: Increased Risk in the Elderly and After Carotid Stenting

Carotid stenosis is a major risk factor for stroke and surgical treatment is key in preventing recurrent ischaemic events. Previous randomised trials have demonstrated the net benefit of surgery for significant symptomatic carotid stenosis but, with present day medical treatment, there is limited evidence on the risk of late ipsilateral ischaemic stroke (IS) and its main risk factors.

Revascularization strategies in patients with multivessel coronary artery disease: a Bayesian network meta-analysis.

Summary Treatment modalities for multivessel disease have rapidly evolved, yet the preferred strategy remains controversial. This meta-analysis compared outcomes after on-pump (ONCAB), off-pump coronary artery bypass grafting (OPCAB), percutaneous coronary intervention (PCI) or hybrid coronary revascularization. A comprehensive search for observational studies and randomized controlled trials published by August 2020 was performed. A Bayesian network meta-analysis was conducted for early (<30 days) and late (>12 months) outcomes. A total of 119 studies were included (n = 700 458 patients). The main analysis was confined to 31 randomized controlled trials (n = 24 932 patients). PCI was associated with lower early mortality [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.31–0.79] and stroke (OR 0.22, 95% CI 0.06–0.60) rates compared with ONCAB, whereas a reduced risk of early myocardial infarction was observed with OPCAB compared with ONCAB (OR 0.53, 95% CI 0.32–0.83). Late target vessel revascularization and major adverse cardiac and cerebrovascular events were both increased with PCI compared with ONCAB, OPCAB and hybrid coronary revascularization (by 127–203% and 59–64%, respectively), and late major adverse cardiac events were increased in PCI compared with ONCAB and OPCAB (by 64% and 59%). However, PCI was associated with a significantly lower risk of late stroke compared with ONCAB (OR 0.70, 95% CI 0.52–0.89). Sensitivity analyses (i) including observational studies and (ii) limiting to studies with recent cohorts confirmed the findings of the main analysis. Surgical approaches for revascularization remain superior to PCI in patients with multivessel disease. Hybrid coronary revascularization might be viable for some patients, although more evidence from randomized controlled trials is warranted.

Effect of Age at Pediatric Stroke on Long-term Cognitive Outcome.

Background and ObjectivesTo investigate the effect of age at pediatric arterial ischemic stroke on long-term cognitive outcome in order to identify patients particularly at risk for the development of long-term cognitive sequelae.MethodsThis cross-sectional study included patients in the chronic phase of stroke (>2 years after stroke) previously diagnosed with neonatal or childhood arterial ischemic stroke and a control group. Participants with active epilepsy, severe learning difficulties, or behavioral problems hindering the cognitive assessment were excluded. Several cognitive domains, including intelligence, executive functions (working memory, inhibition, and cognitive flexibility), processing speed, memory, letter fluency, and visual-motor skills were assessed with neuropsychological tests. Cognitive long-term outcome was compared across patients after neonatal stroke (stroke between 0 and 28 days of life), early childhood stroke (stroke between 29 days and <6 years), and late childhood stroke (stroke between ≥6 and <16 years).ResultsFifty-two patients after neonatal or childhood arterial ischemic stroke (median age 15.3 years, interquartile range [IQR] 10.6–18.7) and 49 healthy controls (median age 13.6 years, IQR 9.8–17.2) met the inclusion criteria. Cognitive outcome was significantly worse in the pediatric stroke group compared to the control group. A nonlinear effect of age at stroke (irrespective of lesion size and lesion location) was found for cognitive flexibility, processing speed, and verbal learning with early childhood stroke (29 days to <6 years), showing significantly worse cognitive outcome compared to neonatal or late childhood stroke (p < 0.05, false discovery rate–corrected).DiscussionAge at stroke is an important factor for poststroke recovery and modulates long-term cognitive outcome irrespective of lesion size and lesion location. Children after early childhood stroke are at particular risk for long-term alterations in cognitive functions.

Timing to Carotid Endarterectomy Affects Early and Long Term Outcomes of Symptomatic Carotid Stenosis.

The aim of this study is to evaluate early and long-term outcomes according to the timing to carotid endarterectomy (CEA) of symptomatic carotid stenosis. Consecutive CEAs with selective shunting for symptomatic carotid stenosis ≥50% performed between 2009 and 2020. Patients had acute neurological impairment on presentation, defined as <5 points on the National Institutes of Health Stroke Scale (NIHSS). We grouped patients according to time between index event and CEA: the first group was operated between 0 and 2 days, the second group between 3 and 7 days, the third group between 8 and 14 days and the last group after 15 days. Thirty-day neurological status improvement was defined as a decrease (≥1) in the 30-day NIHSS score versus NIHSS score immediately before surgery. Five hundred CEAs were performed. The perioperative combined stroke and mortality rate was 3.6% (18/500), representing a perioperative mortality rate of 0.2 (n=1) and stroke rate of 3.4% (n=17). Overall freedom from stroke was 95% at 1 year, 89 % at 6 years, and 88% at 10 years. Annual stroke rate was 0.6% after the 30-day period. Thirty-day improvement in neurologic status occurred in 103 patients (20.6%), while in 380 (76%) neurologic status was unchanged, and 17 (3.4%) experienced worsening of their neurologic status. Patients treated within 7 days from the index event had significant benefit (OR=2.6) in the 30-day neurological improvement versus those treated after 7 days from the index event. Timing to CEA <2 days increased significantly the risk of late stroke (OR=9.7). The ideal timing for performing CEA is between 3 and 7 days from the index event if NIHSS <5 as it is associated with the best rates of improvement in neurological status and durability in the long term. Very early CEA (<48 hrs) was associated with increased late stroke occurrence.

Long-term prognostic value of vasodilator stress cardiac magnetic resonance in patients with atrial fibrillation.

AimsAlthough the prevalence of coronary artery disease (CAD) is high among patients with atrial fibrillation (AF), studies on stress perfusion cardiac magnetic resonance (CMR) imaging frequently exclude patients with AF, and its prognostic and diagnostic value in high‐risk patients with suspected or known CAD remains unclear.Methods and resultsIn this longitudinal cohort study, we included 164 consecutive patients with AF during vasodilator perfusion CMR. Diagnostic value was evaluated regarding invasive coronary angiography in a subset of patients. We targeted a follow‐up of >5 years and used CMR results as stratification, and the primary outcome was major adverse cardiac events [MACE, cardiovascular (CV) death and myocardial infarction (MI)]. Secondary outcomes included late coronary revascularization or stroke and the components of the primary outcome. Of the whole cohort (73.8% male, mean age 72.2 years ± 7.8 SD), 99.4% were successfully scanned (163/164 patients). Median CHA2DS2‐VASc score was 4 [interquartile range (IQR) 3–5], and median 10‐year risk for CV events based on SMART risk score was high (24%, IQR 16–32%). Thirty‐two patients (19.6%) presented with ischaemia and 52 patients (31.9%) with late gadolinium enhancement (LGE). A combination of LGE and inducible ischaemia was present in 20 patients (12.3%). Diagnostic accuracy was 86.2% [confidence interval (CI) 68.3–96.1%]. The median follow‐up was 6.6 years (IQR 3.6–7.8). Ischaemia in vasodilator perfusion CMR was significantly associated with the occurrence of MACE [P < 0.01; hazard ratio (HR) 2.65, CI 1.39–5.08], as well as LGE (P = 0.03; 1.74, CI 1.07–3.64) and the combination of both (P < 0.01; HR 2.67, CI 1.59–5.62). After adjustment by age, left ventricular ejection fraction, and the presence of diabetes, ischaemia in vasodilator perfusion CMR remained significantly associated with the occurrence of MACE (2.10, CI 1.08–4.10; P = 0.03). In secondary endpoint analysis, there was a significant association of ischaemia in CMR with CV death (P < 0.05; HR 1.93, CI 0.95–3.9) and MI (P < 0.01; HR 13, CI 1.35–125.4), while no significant association was found regarding the occurrence of revascularization (P = 0.45; HR 1.43, CI 0.57–3.58) or stroke (P = 0.99; HR 0.99, CI 0.21–2.59).ConclusionsVasodilator stress perfusion CMR demonstrated an excellent diagnostic and significant prognostic value at long‐term follow‐up in high‐risk patients with persistent AF and suspected or known CAD.

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes.

The balance between neurodegeneration, neuroinflammation, neuroprotection, and COVID-19-directed therapy may underly the heterogeneity of SARS-CoV-2′s neurological outcomes. A total of 105 patients hospitalized with a diagnosis of COVID-19 had serum collected over a 6 month period to assess neuroinflammatory (MIF, CCL23, MCP-1), neuro-injury (NFL, NCAM-1), neurodegenerative (KLK6, τ, phospho τ, amyloids, TDP43, YKL40), and neuroprotective (clusterin, fetuin, TREM-2) proteins. These were compared to markers of nonspecific inflammatory responses (IL-6, D-dimer, CRP) and of the overall viral burden (spike protein). Data regarding treatment (steroids, convalescent plasma, remdasavir), pre-existing conditions, and incidences of strokes were collected. Amyloid β42, TDP43, NF-L, and KLK6 serum levels declined 2–3 days post-admission, yet recovered to admission baseline levels by 7 days. YKL-40 and NCAM-1 levels remained elevated over time, with clusters of differential responses identified among TREM-2, TDP43, and YKL40. Fetuin was elevated after the onset of COVID-19 while TREM-2 initially declined before significantly increasing over time. MIF serum level was increased 3–7 days after admission. Ferritin correlated with TDP-43 and KLK6. No treatment with remdesivir coincided with elevations in Amyloid-β40. A lack of convalescent plasma resulted in increased NCAM-1 and total tau, and steroidal treatments did not significantly affect any markers. A total of 11 incidences of stroke were registered up to six months after initial admission for COVID-19. Elevated D-dimer, platelet counts, IL-6, and leukopenia were observed. Variable MIF serum levels differentiated patients with CVA from those who did not have a stroke during the acute phase of COVID-19. This study demonstrated concomitant and opposite changes in neurodegenerative and neuroprotective markers persisting well into recovery.

Safety and Efficacy of Rapamycin-Eluting Vertebral Stents in Patients With Symptomatic Extracranial Vertebral Artery Stenosis

Background and Purpose: Drug-eluting stents generally have superior performance to bare metal stents in the treatment of vertebral artery stenosis (VAS). This prospective, multicenter, and single-arm clinical trial was initiated to assess in-stent restenosis (ISR) and midterm outcome after rapamycin-eluting stent placement in patients with symptomatic extracranial VAS.Methods: The subjects underwent angiographic follow-up at 6 months and final clinical follow-up at 12 months. The primary efficacy endpoint was ISR at 6 months. Secondary endpoints included technical success, target lesion-related transient ischemic attack (TIA), stroke, or death, and all-cause TIA, stroke, or death during the 12-month follow-up period.Results: A total of 104 stents were implanted in the 101 patients and 83 patients (82.2%) completed angiographic follow-up at 6 months. The technical success rate was 86.1% (87/101); mean in-stent stenosis rate was 25.1 ± 17.1% and ISR rate was 5.9% (95% CI: 0.8–10.9%). All the patients with ISR were completely asymptomatic and no stent fractures were observed during angiographic follow-up. At the 12-month clinical follow-up, target lesion-related TIA, stroke, or death had occurred in two (2.0%) patients and all-cause TIA, stroke, or death had occurred in six (6.1%) patients.Conclusion: The placement of rapamycin-eluting stents in patients with symptomatic extracranial VAS yields favorable ISR results and showed a trend of favorable safety outcomes including low rates of perioperative complications and late stroke. However, further study is needed to establish the long-term clinical benefits of this stent in the treatment of VA disease.

Low Incidence of Late Ipsilateral Ischaemic Stroke After Treatment for Symptomatic Carotid Stenosis in Sweden 2008–2017: Increased Risk in the Elderly and After Carotid Stenting

Carotid stenosis is a major risk factor for stroke and surgical treatment is key in preventing recurrent ischaemic events. Previous randomised trials have demonstrated the net benefit of surgery for significant symptomatic carotid stenosis but, with present day medical treatment, there is limited evidence on the risk of late ipsilateral ischaemic stroke (IS) and its main risk factors. Ipsilateral IS after the peri-operative period (≤ 30 days) was investigated in a nationwide, registry based cohort study of patients treated for symptomatic carotid stenosis in Sweden between 2008 - 2017. The Swedish National Registry for Vascular Surgery (Swedvasc) was used to establish the cohort, and the Swedish stroke registry (Riksstroke), combined with hospital records, was used to determine outcome. Stroke of any type and all cause mortality after the peri-operative period were studied as secondary outcomes. Cox regression was used to analyse associations between clinical factors and outcomes. In total, 7 589 patients (mean age 72 ± 8 years, 68% men) were followed for 4.2 ± 2.6 years. Ipsilateral IS occurred in 232 patients corresponding to a yearly incidence of 0.73%. Age above 80 years compared with 65 - 79 years was associated with an increased risk of ipsilateral IS (adjusted HR 1.94, 95% CI 1.43 - 2.65). Carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) was also associated with increased risk (adjusted HR 3.20, 95% CI 2.03 - 5.03). Stroke of any type occurred in 7.7% of patients, and 19.6% of patients died during the follow up period. The incidence of ipsilateral IS after treatment for symptomatic carotid stenosis in Sweden 2008-2017 was low, demonstrating the effectiveness and durability of surgery in a real world setting. Only age above 80 years and CAS compared with CEA were associated with increased risk of ipsilateral IS.

Study Criteria Applied to Real Life-A Multicenter Analysis of Stroke Patients Undergoing Endovascular Treatment in Clinical Practice.

BackgroundRandomized controlled clinical trials (RCT) have demonstrated the efficacy of endovascular treatment in anterior circulation large vessel occlusions. However, outcome of patients treated in daily practice differs from the results of the clinical trials. We hypothesize that this is attributable to the study criteria and that application of the criteria on patients undergoing endovascular therapy in daily routine would improve their outcome.Methods and ResultsData from a multicenter prospective registry of GSR‐ET (German Stroke Registry – Endovascular Treatment) was used. Inclusion criteria and selectivity of SWIFT‐PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment trial), MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial), ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times trial), DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake‐Up and Late Presenting Strokes Undergoing Neurointervention with Trevo trial) and DEFUSE‐3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial) trials were analyzed. Baseline characteristics, procedural and outcome data of patients from GSR‐ET before and after selection were compared with the results of the RCTs. Furthermore, outcome of patients who underwent endovascular treatment despite not fulfilling the RCT criteria was analyzed. A total of 2611 patients were included (median age, 75 years; 49.6% women; median National Institute of Health Stroke Scale, 16). A minority of patients met all inclusion criteria, ranging from 3% (DEFUSE‐3 criteria) to 35% (MR CLEAN criteria). Of the patients fulfilling the MR CLEAN criteria, 41% of patients had a good clinical outcome, compared with 34% of patients that did not fulfill MR CLEAN criteria.ConclusionsThe RCTs represent a selected population with higher rates of good clinical outcome compared with daily practice. The good outcomes of RCTs can be reproduced in clinical routine in patients who fulfill the RCT inclusion criteria. Furthermore, patients who did not meet the criteria of the RCT still had substantial rates of good clinical outcome.

Automated Brain Perfusion Imaging in Acute Ischemic Stroke: Interpretation Pearls and Pitfalls.

Recent advancements in computed tomography technology, including improved brain coverage and automated processing of the perfusion data, have reinforced the use of perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. The DAWN (Diffusion Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trials have established the benefit of endovascular thrombectomy in patients with acute ischemic stroke with anterior circulation large vessel occlusion up to 24 hours of last seen normal, using perfusion imaging-based patient selection. The compelling data has prompted stroke centers to increasingly introduce automated perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. We present a comprehensive overview of the acquisition and interpretation of automated perfusion imaging in patients with acute ischemic stroke with a special emphasis on the interpretation pearls, pitfalls, and stroke mimicking conditions.

Low Incidence of Ischemic Stroke Associated With Thrombus Aspiration in STEMI Patients Undergoing Primary PCI.

Thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) was recommended to minimize distal embolization and to reduce thrombus burden prior to PPCI. Subsequent randomized trials showed no mortality benefit from TA and suggested an increased risk of stroke up to 180 days following TA, although it was not obvious that the procedure alone caused the strokes. This study retrospectively analyzed the periprocedural stroke rate in a series of STEMI patients treated with TA and PPCI at a single, large, tertiary hospital, where a rigorous uniform protocol of aspiration was used in all patients. Of 3734 patients, 1404 patients (38%; group 1) underwent TA as part of the PPCI procedure and 2330 patients (62%; group 2) did not undergo TA. There were no significant clinical differences between the 2 groups. In total, there were 20 strokes (0.54%), with 3 (0.2%) occurring in group 1, and 17 (0.7%) occurring in group 2 (P=.04). The majority of strokes occurred within 5 days of the procedure, and 3 (0.08%) were hemorrhagic. There were 22 intraprocedural deaths (0.6%), related to cardiogenic shock. There were no intraprocedural strokes. Very low stroke rates immediately post STEMI were seen in patients undergoing TA and PPCI in this real-world study. TA can be performed safely in STEMI patients undergoing PPCI with a short-term stroke risk equivalent to risk without TA. Further studies may be needed to explain the increased incidence of late stroke noted after TA and elucidate causative mechanisms.

Not All Lesioned Tissue Is Equal: Identifying Pericavitational Areas in Chronic Stroke With Tissue Integrity Gradation via T2w T1w Ratio.

Stroke-related tissue damage within lesioned brain areas is topologically non-uniform and has underlying tissue composition changes that may have important implications for rehabilitation. However, we know of no uniformly accepted, objective non-invasive methodology to identify pericavitational areas within the chronic stroke lesion. To fill this gap, we propose a novel magnetic resonance imaging (MRI) methodology to objectively quantify the lesion core and surrounding pericavitational perimeter, which we call tissue integrity gradation via T2w T1w ratio (TIGR). TIGR uses standard T1-weighted (T1w) and T2-weighted (T2w) anatomical images routinely collected in the clinical setting. TIGR maps are analyzed with relation to subject-specific gray matter and cerebrospinal fluid thresholds and binned to create a false colormap of tissue damage within the stroke lesion, and these are further categorized into low-, medium-, and high-damage areas. We validate TIGR by showing that the cerebral blood flow within the lesion reduces with greater tissue damage (p = 0.005). We further show that a significant task activity can be detected in pericavitational areas and that medium-damage areas contain a significantly lower magnitude of hemodynamic response function than the adjacent damaged areas (p < 0.0001). We also demonstrate the feasibility of using TIGR maps to extract multivariate brain–behavior relationships (p < 0.05) and show general agreement in location compared to binary lesion, T1w-only, and T2w-only maps but that the extent of brain behavior maps may depend on signal sensitivity as denoted by the sparseness coefficient (p < 0.0001). Finally, we show the feasibility of quantifying TIGR in early and late subacute stroke phases, where higher-damage areas were smaller in size (p = 0.002) and that lesioned voxels transition from lower to higher damage with increasing time post-stroke (p = 0.004). We conclude that TIGR is able to (1) identify tissue damage gradient within the stroke lesion across different post-stroke timepoints and (2) more objectively delineate lesion core from pericavitational areas wherein such areas demonstrate reasonable and expected physiological and functional impairments. Importantly, because T1w and T2w scans are routinely collected in the clinic, TIGR maps can be readily incorporated in clinical settings without additional imaging costs or patient burden to facilitate decision processes related to rehabilitation planning.

Robotics-assisted epicardial left atrial appendage clip exclusion.

ObjectivesWe demonstrate the feasibility and safety of robotics-assisted left atrial appendage clip exclusion in clinical practice.MethodsAnalysis of a single center robotics-assisted left atrial appendage clip exclusion experience using an epicardial linear clip device in patients with atrial fibrillation with high-risk of thromboembolic stroke and intolerance to oral anticoagulants.ResultsDuring the period from December 2017 to September 2020, we performed 42 robotics-assisted left atrial appendage clip exclusions in response to increased risk of bleeding in patients with atrial fibrillation and intolerance to oral anticoagulants. The average congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease score was 5.2 ± 1.6 and hypertension, abnormal liver or kidney function, stroke, bleeding, labile international normalized ratio, elderly, drugs (aspirin, other antiplatelets, or anticoagulants) score was 4.5 ± 0.9. No patients died intraoperatively or within 30 days, or due to conversion to thoracotomy, intraoperative complications, or failure to apply the clip satisfactorily. The procedure was successfully completed despite pericardial adhesions in 2 patients with prior coronary bypass grafts and 3 with postpericarditis scars. Intraoperative transesophageal echocardiography was performed in 38 out of 42 patients; satisfactory exclusion with left atrial appendage stump <5 mm was confirmed in all. Average length of stay was 3.4 ± 3 days with 12 out of 42 patients discharged within 24 hours. Oral anticoagulants were discontinued in 41 out of 42 patients and no cases of 30-day stroke, myocardial ischemia, or new arrhythmias were observed. One case of hemothorax required thoracoscopy a day later. There was no reported thromboembolic stroke or transient ischemic attack at 12 months. One case of late lacunar stroke was due to in situ small intracranial vessel thrombosis without left atrial appendage thrombus on imaging.ConclusionsRobotics-assisted left atrial appendage clip exclusion is a safe and feasible minimally invasive method for left atrial appendage management in patients with atrial fibrillation with intolerance to oral anticoagulants and increased risk of thromboembolic stroke.

Serial ASPECTS in the DAWN Trial: Infarct Evolution and Clinical Impact.

The impact of baseline ischemia on Alberta Stroke Program Early CT Score (ASPECTS) and evolution over 24 hours may be distinct in late thrombectomy. We analyzed predictors of serial ASPECTS and clinical outcomes in the DAWN trial (Diffusion-Weighted Imaging or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). The DAWN Imaging Core Laboratory independently scored ASPECTS at baseline and 24 hours. Descriptive statistics characterized ASPECTS on computed tomography/magnetic resonance imaging at baseline and 24 hours, delineating ASPECTS change over 24 hours. 206 subjects (mean age 70.0±13.7 years; 54.9% (n=113) female; baseline National Institutes of Health Stroke Scale median (interquartile range) 17 (13, 21) were included. Baseline ASPECTS was median (interquartile range) 8.0 (7–8), with 92/205 (44.9%) between 0 and 7 and 113/205 (55.1%) 8 and 10. 24-hour ASPECTS was median 6.0 (4–8), with ASPECTS change or infarct evolution having median −1, ranging from −8 to +2. Multivariable logistic regression showed older age (odds ratio [OR] for 10-year interval, 1.26 [95% CI, 1.02–1.55], P=0.030) and dyslipidemia (OR, 1.84 [95% CI, 1.06–3.19], P=0.031) were independently associated with higher baseline ASPECTS. Higher 24-hour ASPECTS was predicted by endovascular treatment (OR, 2.76 [95% CI, 1.58–4.81], P=0.0004), baseline glucose <150 mg/dL (OR, 2.86 [95% CI, 1.50–5.46], P=0.001), lower baseline National Institutes of Health Stroke Scale (OR, 0.93 [95% CI, 0.89–0.98], P=0.010), and older age (OR for 10-year interval, 1.25 [95% CI, 1.01–1.55], P=0.041). Internal carotid artery lesion location (OR, 0.47 [95% CI, 0.24–0.89], P=0.021) was inversely related to 24-hour ASPECTS. Good clinical outcome (day 90 modified Rankin Scale score 0–2) was predicted by 24-hour ASPECTS (OR, 1.46 [95% CI, 1.08–1.96], P=0.014). Extensive infarct evolution (ASPECTS decrease ≥6) occurred in 14/201 (7.0%). Elevated baseline serum glucose ≥150 mg/dL was a predictor of ASPECTS decrease of ≥4 points (OR, 2.78 [95% CI, 1.21–6.35] P=0.016) as was internal carotid artery occlusion (OR, 2.49 [95% CI, 1.05–5.88]; P=0.038). ASPECTS change was influenced by treatment arm (P=0.001 by Wilcoxon), including 0 ASPECTS change in 42/105 (40.0%) of the endovascular arm and only 20/96 (20.8%) of the medical arm. DAWN subjects enrolled with small infarct cores had a broad range of baseline ASPECTS. Twenty-four-hour ASPECTS, strikingly influenced by endovascular therapy, predicted good clinical outcomes. https://www.clinicaltrials.gov; Unique identifier: NCT02142283.

Management of patients with asymptomatic carotid stenosis may need to be individualized: a multidisciplinary call for action. Republication of J Stroke 2021;23:202-212.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Risk of Stroke After Transcatheter Aortic Valve Implantation: Epidemiology, Mechanism, and Management.

Transcatheter aortic valve implantation (TAVI) has become an established and increasingly used approach for management of severe symptomatic aortic stenosis, showing similar or even superior outcomes compared with standard surgical aortic valve replacement (SAVR). Stroke after TAVI is a relatively rare, but serious complication, associated with potential prolonged disability and increased mortality. The overall incidence of 30-day stroke in TAVI patients is 3%-4%, but varies between different trials. Initial data suggested a higher risk of stroke after TAVI when compared with SAVR. The association between subclinical leaflet thrombosis and cerebral embolism, presented as stroke, transient ischemic accident, or silent cerebral ischemia is not entirely elucidated yet. Moreover, TAVI for severe bicuspid aortic stenosis is a relatively new issue, bicuspid anatomy being initially excluded from the pivotal clinical trials investigating TAVI procedure. Efficient stroke prevention strategies are under investigation. In the present manuscript, we used the available published data from the most relevant clinical trials, registries, and meta-analysis of patients from different risk categories who underwent TAVI or SAVR. Predictors of acute stroke are mainly procedure related. Technological development, improvements in bioprosthesis valve delivery catheters, and implantation technique may explain the decrease of stroke over the years since the beginning of TAVI procedures. The overall evidences confirm similar or lower rate of stroke in TAVI versus SAVR. Risk predictors for acute stroke after TAVI are generally related to procedural factors, whereas late stroke is mainly associated with patient characteristics, with a variable impact on cognitive function. The optimal choice for the antithrombotic treatment in TAVI for stroke prevention is yet to be determined. Current data do not support routine use of cerebral embolic protection devices during TAVI.

Coronary artery bypass grafting versus percutaneous coronary intervention in end-stage kidney disease: A systematic review and meta-analysis of clinical studies.

The most significant complication of end-stage kidney disease (ESKD) is cardiovascular disease, mainly coronary artery disease (CAD). Although the effective treatment of CAD is an important prognostic factor, whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for treating CAD in this group of patients is still controversial. We searched Pubmed/Medline, Web of Science, Embase, the Cochrane Central Register of Controlled Trials articles that compared the outcomes of CABG versus PCI in patients with ESKD requiring dialysis. A total of 10 observational studies with 39,666 patients were included. Our analysis showed that when compared to PCI, CABG had lower risk of need for repeat revascularization (relative risk [RR]=2.25, 95% confidence interval [CI] 2.1-2.42, p < 0.00001) and cardiovascular death (RR=1.19, 95% CI 1.14-1.23, p < 0.00001) and higher risk for short-term mortality (RR=0.43, 95% CI 0.38-0.48, p < 0.00001). There was no statistically significant difference between the PCI and CABG groups in the risk for late mortality (RR=1.05, 95% CI 0.97-1.14, p=0.25), myocardial infarction (RR=1.05, 95% CI 0.46-2.36, p=0.91) or stroke (RR=1.02, 95% CI 0.64-1.61, p=0.95). This meta-analysis showed that in ESKD patients requiring dialysis, CABG was superior to PCI in regard to cardiovascular death and need for repeat revascularization and inferior to PCI in regard to short term mortality. However, this meta-analysis has limitations and needs confirmation with large randomized controlled trials.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient’s life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.