High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging.

BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS. METHODS AND RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2). CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.

Magnetic resonance imaging for diagnostic workup of embolic stroke of undetermined source: A systematic review.

BACKGROUND: Embolic stroke of undetermined source (ESUS) refers to ischemic stroke where the underlying cause of thromboembolism cannot be found despite the recommended diagnostic workup. Unidentified source of emboli hinders clinical decision-making and patient management with detrimental consequences on long-term prognosis. The rapid development and versatility of magnetic resonance imaging (MRI) make it an appealing addition to the diagnostic routine of patients with ESUS for the assessment of potential vascular and cardiac embolic sources. AIMS: To review the use of MRI in the identification of cardiac and vascular embolic sources in ESUS and to assess the reclassification value of MRI examinations added to the conventional workup of ESUS. SUMMARY OF REVIEW: We reviewed the use of cardiac and vascular MRI for the identification of a variety of embolic sources associated with ESUS, including atrial cardiomyopathy, left ventricular pathologies, and supracervical atherosclerosis in carotid and intracranial arteries and in distal thoracic aorta. The additional reclassification after MRI examinations added to the workup of patients with ESUS ranged from 6.1% to 82.3% and varied depending on the combination of imaging modalities. CONCLUSION: MRI techniques allow us to identify additional cardiac and vascular embolic sources and may further decrease the prevalence of patients with the diagnosis of ESUS.

Sex-Specific Risk Factors of Nonstenotic Carotid Plaque in Embolic Stroke of Unknown Source: A Case-Control Study.

BACKGROUND: Many ischemic strokes are diagnosed as embolic strokes of undetermined source (ESUS). Recent evidence suggests that nonstenotic carotid plaque (nsCP) may be a substantial contributor to the risk for ESUS. We aimed to investigate the risk factor profile associated with nsCP in ESUS and defined stroke etiologies. METHODS: In this retrospective case-control study, we investigated consecutive patients with acute ischemic stroke due to ESUS, small-vessel disease, or cardioembolism proven by magnetic resonance imaging. The association of vascular risk factors age, arterial hypertension, diabetes, dyslipoproteinemia, body mass index, alcohol consumption, tobacco use, kidney failure, and history of stroke with the presence of nsCP was investigated using binary logistic regression analysis and further stratified by stroke etiology and sex. RESULTS: In total, 609 patients (median age, 76 years; 46% women) who were treated from 2018 to 2020 were considered. In patients with ESUS, sex played a more important role for the prevalence of nsCP than in defined etiologies. Female patients with ESUS had lower odds of exhibiting nsCP compared with male patients with ESUS (adjusted odds ratio, 0.36 [95% CI, 0.15-0.86]). In male patients with ESUS, we observed that age (adjusted odds ratio per 10-year increase, 2.55 [95% CI, 1.26-5.17]) and hypertension (adjusted odds ratio, 2.49 [95% CI, 0.56-11.1]) were the main risk factors for nsCP, whereas in female patients with ESUS also tobacco use was particularly relevant (adjusted odds ratio, 3.71 [95% CI, 0.61-22.5]). These results were in line with a sensitivity analysis in nsCP located ipsilateral to the infarct. CONCLUSIONS: Sex differences play an important role in nsCP prevalence in patients with ESUS. These findings may have important implications for the management in targeted secondary prevention following ESUS.

Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study.

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

Incidence and predictors of stroke and silent cerebral embolism following very high-power short-duration atrial fibrillation ablation.

AIMS: Cerebral thrombo-embolism is a dreaded complication of pulmonary vein isolation (PVI) for atrial fibrillation; its surrogate, silent cerebral embolism (SCE) can be detected by diffusion-weighted brain magnetic resonance imaging (bMRI). Initial investigations have raised a concern that very high-power, short-duration (vHPSD; 90 W/4 s) temperature-controlled PVI with the QDOT Micro catheter may be associated with a higher incidence of SCE compared with low-power long-duration ablation. We aimed to assess the incidence of procedural complications of vHPSD PVI with an emphasis on cerebral safety. METHODS AND RESULTS: We enrolled 328 consecutive patients undergoing their PVI procedure using vHPSD. A subgroup of 61 consecutive patients underwent diffusion-weighted bMRI within 24 h of the procedure, and incidence and predictors of SCE were studied. The mean procedure time and left atrial dwell time for the overall cohort were 69.6 ± 24.1 and 46.5 ± 21.5 min, respectively. First-pass isolation was achieved in 82%. No stroke or transient ischaemic attack occurred. Silent cerebral embolism was identified in 5 of 61 patients (8.2%). Silent cerebral embolism following procedures was significantly associated with lower baseline generator impedance (105.8 vs. 112.6 Ω, P < 0.0001) and with intermittent loss of catheter-tissue contact during ablation (14.1% vs. 6.1%, P < 0.0001). CONCLUSION: Very high-power, short-duration PVI is a safe technique with an excellent acute success rate. Silent cerebral embolism incidence in our cohort was below the previously reported range, with no clinically overt cerebral complications. Lower baseline generator impedance and loss of contact during ablation may contribute to a higher risk of SCEs.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Predictors of Cerebral Embolic Debris During Transcatheter Aortic Valve Replacement: The SafePass 2 First-in-Human Study.

Transcatheter aortic valve replacement (TAVR) generates significant debris, and strategies to mitigate cerebral embolization are needed. The novel Emboliner embolic protection catheter (Emboline, Inc., Santa Cruz, California) is designed to capture all particles generated during TAVR. This first-in-human study sought to assess the safety and feasibility of the device and to characterize the distribution and histopathology of the debris generated during TAVR. The SafePass 2 study was a prospective, nonrandomized, multicenter, single-arm investigation of the Emboliner device. Primary end points included 30-day major adverse cardiac and cerebrovascular events (MACCE) and technical performance. Computed tomography angiography was analyzed by an independent core laboratory, and filters were sent for histopathology of captured debris. Predictors of particle number were identified using >150 µm and >500 µm size thresholds. Of 31 subjects enrolled, technical success was 100%, and 30-day MACCE was 6.5% (2 cerebrovascular accidents, with 1 attributed to subtherapeutic dosing of rivaroxaban along with atrial fibrillation and the other to possible previous small ischemic strokes on magnetic resonance imaging; neither MACCE event had a causal relation to the Emboliner). All filters contained debris, with a median of 191.0 particles >150 µm and 14.0 particles >500 µm. Histopathology revealed mostly acute thrombus and valve or arterial tissue with lesser amounts of calcified tissue. A history of atrial fibrillation predicted a greater number of particles >500 µm (p = 0.0259) and its presence on admission was associated with 4.1 times more particles >150 µm (p = 0.0130) and 8.1 times more particles >500 µm (p = 0.0086). Self-expanding valves were associated with twice the number of particles >150 µm (p = 0.0281). TASK score was positively correlated with number of particles >500 µm (p = 0.0337). The Emboliner device was safe and feasible. Emboli after TAVR appear more numerous than previously documented. Atrial fibrillation, higher TASK score, and self-expanding valve use conferred higher embolic burden. Notably, none of the tested computed tomography angiography features were able to identify with higher embolic risk. Larger-scale studies are needed to identify high-risk patients for selective embolic protection device use.

Outcomes of Cerebral Embolic Protection for Bicuspid Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background There was limited high-quality evidence that illuminated the efficiency of cerebral embolic protection (CEP) use during transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) stenosis. Methods and Results In this retrospective cohort study, patients with BAV stenosis undergoing TAVR with or without CEP were identified by querying the National Inpatient Sample database. The primary end point was any stroke during the hospitalization. The composite safety end point included any in-hospital death and stroke. We applied propensity score-matched analysis to minimize standardized mean differences of baseline variables and compare in-hospital outcomes. From July 2017 to December 2020, 4610 weighted hospitalizations with BAV stenosis undergoing TAVR were identified, of which 795 were treated with CEP. There was a significant increase in the CEP use rate for BAV stenosis (P-trend <0.001). A total of 795 discharges with CEP use were propensity score matched to 1590 comparable discharges but without CEP. CEP use was associated with a lower incidence of in-hospital stroke (1.3% versus 3.8%; P<0.001), which in multivariable regression was also independently associated with the primary outcome (adjusted odds ratio=0.38 [95% CI, 0.18-0.71]; P=0.005) and the safety end point (adjusted odds ratio=0.41 [95% CI, 0.22-0.68] P=0.001). Meanwhile, no significant difference was found in the cost of hospitalization ($46 629 versus $45 147; P=0.18) or the risk of vascular complications (1.9% versus 2.5%; P=0.41). Conclusions This observational study supported CEP use for BAV stenosis, which was independently associated with less in-hospital stroke without burdening the patients with a high hospitalization cost.

Surgical and percutaneous left atrial appendage intervention: silent cerebral embolism considerations.

OBJECTIVES: Left atrial appendage intervention is an alternative to oral anticoagulation for thromboprophylaxis in atrial fibrillation. The aim of our study was to compare the incidence of silent cerebral embolisms after surgical and percutaneous intervention and to identify the risk factors for procedure-related silent cerebral embolisms after intervention. METHODS: This prospective observational study included consecutive atrial fibrillation patients from 2 independent cohorts (left atrial appendage excision (LAAE) cohort and left atrial appendage occlusion cohort) between September 2018 and December 2020. All patients underwent cerebral magnetic resonance imaging before and after the procedure. Silent cerebral embolism was defined as new focal hyperintense lesions detected only on postprocedural sequence. RESULTS: Thirty-two patients from the LAAE cohort and 42 patients from the occlusion cohort were enrolled. A significantly lower incidence of silent cerebral embolism was observed in the LAAE cohort as compared with occlusion (6.3% vs 54.8%, P < 0.001). In the left atrial appendage occlusion cohort, patients who developed silent cerebral embolism after the procedure had significantly higher CHA2DS2-VASc scores [odds ratio (OR) 2.172; 95% confidence interval (CI) 1.149-4.104; P = 0.017], longer occlusion placement time (OR 1.067; 95% CI 1.018-1.118; P = 0.006) and lower peak activated clotting time level after transseptal puncture (OR 0.976; 95% CI 0.954-0.998; P = 0.035). CONCLUSIONS: The incidence of procedure-related silent cerebral embolism was strikingly lower in patients with LAAE than in patients with occlusion. More cardiovascular comorbidities, longer occlusion placement time and lower activated clotting time level were significantly associated with the development of procedure-related silent cerebral embolism.

Reclassification and risk stratification of embolic stroke of undetermined source by ASCOD phenotyping.

BACKGROUND: Common vascular diseases underlying stroke, including atherosclerosis, small-vessel disease (SVD), and cardioembolic pathology, can be present in patients with embolic stroke of undetermined source (ESUS), although these are not direct causes of stroke. AIMS: To describe the frequency and degree of the three major diseases using atherosclerosis, SVD, cardiac pathology, other causes, and dissection (ASCOD) phenotyping and to assess their prognostic implications in ESUS. METHODS: In this prospective observational study, 221 patients with ESUS within 1 week of onset were consecutively enrolled and followed up for 1 year. Vascular diseases associated with stroke were assessed using the ASCOD classification. The primary outcome was a composite of nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: Among 221 patients (mean age, 69.6 years; male, 59.7%), 135 (61.1%), 102 (46.2%), and 107 (48.4%) had any grade of atherosclerosis (A2 or A3), SVD (S3), and cardiac pathology (C2 or C3), respectively. ESUS patients graded as A2 or A3 (i.e. ipsilateral atherosclerotic plaque, contralateral ⩾ 50% stenosis, or aortic arch plaque) were at a significantly higher risk of composite vascular events than those graded as A0 (i.e. no atherosclerotic disease) (adjusted hazard ratio (95% confidence interval), 2.40 (1.01-5.72). No differences were observed in the event risk between patients with S3 (i.e. magnetic resonance imaging evidence of SVD) and S0 (i.e. no SVD) and between those with C2 or C3 (i.e. presence of any cardiac pathology) and C0 (i.e. no cardiac abnormalities). CONCLUSIONS: Atherosclerotic diseases corresponding to ASCOD grade A2 or A3 were predictive of recurrent vascular events in ESUS patients. Reclassification of ESUS using ASCOD phenotyping provides important clues for risk prediction and may guide optimal management strategies.

Non-stenosing carotid artery plaques in embolic stroke of undetermined source: a retrospective analysis.

BACKGROUND: We aim to identify the association between high-risk carotid plaques and their laterality to stroke in ESUS patient population. We also discuss recurrent stroke events and their laterality to the index stroke. METHODS: This was a retrospective study. We reviewed data for patients with ESUS between June 20, 2016, and June 20, 2021. Using computed tomography angiography, we analyzed plaque features that are associated with ESUS, and then, we identified the recurrent stroke events and characterized lateralization to the index stroke. RESULTS: Out of 1779 patients with cryptogenic ischemic stroke, we included 152 patients who met the criteria for ESUS. High-risk plaque features were found more often ipsilateral to the stroke side when compared contralaterally: plaque ulceration (19.08% vs 5.26%, p < .0001), plaque thickness > 3 mm (19.08% vs 7.24%, p = 0.001), and plaque length > 1 cm (13.16% vs 5.92%, p = 0.0218). There was also a significant difference in plaque component in which both components (soft and calcified) and only soft plaques were more prevalent ipsilaterally (42.76% vs 23.68% and 17.76% vs 9.21%, respectively, p < .0001). Of the 152 patients, 17 patients were found to have a recurrent stroke event, and 47% (n = 8) had an ipsilateral stroke to the index event. Moreover, stroke was bilateral in 41% of the patients (n = 7), and contralateral in 12% (n = 2). CONCLUSION: High-risk plaque features studied here were more prevalent ipsilaterally to the stroke side in ESUS than contralaterally. Multicenter studies are needed to form precise prediction models and scoring systems to help guide treatment, i.e., choice of medical therapy and/or revascularization.

Atrial cardiopathy in young adults with embolic stroke of undetermined source: a myocardial deformation imaging analysis.

BACKGROUND: Atrial cardiopathy (AC) has emerged as a potential pathological thrombogenic atrial substract of embolic stroke of undetermined source (ESUS), even in the absence of atrial fibrillation. Left atrium (LA) myocardial deformation analysis may be of value as a subclinical marker of AC and a predictor of ESUS. AIMS: To compare LA mechanical function between ESUS cases and age and sex-matched controls. METHODS: A single-center analytical study with case-control design was performed. Case group was composed by young patients admitted in the Neurology department from January 2017 to June 2021. Control group was composed by age and sex matched controls recruited from the community. All participants performed echocardiogram and a smaller sample underwent cardiac magnetic resonance. RESULTS: We recruited 31 ESUS patients aged between 18 and 65 years and 31 age and sex matched controls. ESUS patients had a significantly higher prevalence of cardiovascular risk factors and patent foramen ovale (PFO). The prevalence of AC was not different between groups. Echocardiogram parameters, including strain analysis, were similar between groups, except for LA appendage (LAA) ostium variation which was significantly lower in ESUS patients (absolute: 6.5vs8.7mm, p<0.001; relative: 44.5%vs53.4%, p=0.002). After exclusion of patients with PFO, all the results were statistically similar. Regarding cardiac magnetic resonance analysis, there were no statistically significant differences between groups. CONCLUSION: This study shows that in our population atria cardiopathy and atrial function was not associated with ESUS.LAA structural and functional abnormalities may play a major role. The role of LAA in ESUS warrants further studies.

A multicenter prospective randomized study comparing the incidence of periprocedural cerebral embolisms caused by catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation (Embo-Abl study): Study design.

BACKGROUND: Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%-1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%-40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation. METHODS: The aim of the Embo-Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion-weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open-label, controlled, randomized fashion. The primary endpoint of the Embo-Abl study will be the occurrence of MRI-detected SCE 1-3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan. RESULTS: The results of this study are currently under investigation. CONCLUSION: The Embo-Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

Atherosclerosis as a Potential Cause of Deep Embolic Stroke of Undetermined Source: A 3T High-Resolution Magnetic Resonance Imaging Study.

Background The potential causes or sources of embolic stroke of undetermined source (ESUS) vary. This study aimed to investigate the main cause of deep ESUS by evaluating nonstenotic intracranial atherosclerotic plaque. Methods and Results We retrospectively screened consecutive patients with unilateral anterior circulation ESUS. After excluding the patients with possible embolism from an extracranial artery such as aortic arch plaque, carotid plaque, and so on, the enrolled patients with ESUS were categorized into 2 groups: deep ESUS and cortical with/without deep ESUS. All patients underwent intracranial high-resolution magnetic resonance imaging to assess the characteristics of nonstenotic intracranial atherosclerotic plaque. Biomarkers of atrial cardiopathy (ie, P-wave terminal force in lead V1 on ECG, NT-proBNP [N-terminal pro-brain natriuretic peptide] and left atrial diameter) were collected. A total of 155 patients with ipsilateral nonstenotic intracranial atherosclerotic plaque were found, with 76 (49.0%) in deep ESUS and 79 (51.0%) in cortical with/without deep ESUS. We found more prevalent plaque in the M1 segment of the middle cerebral artery and the ostia of the perforator, with a smaller remodeling index plaque burden, and less frequent occurrence of complicated plaque in deep ESUS versus cortical with/without deep ESUS. Higher BNP (brain natriuretic peptide) levels and a higher prevalence of atrial cardiopathy in cortical with/without deep ESUS versus deep ESUS. Moreover, the discrimination of vulnerable plaque for predicting ESUS was significantly enhanced after adjusting for or further excluding patients with deep ESUS. Conclusions The current study provides the first high-resolution magnetic resonance imaging evidence that cortical with/without deep ESUS and deep ESUS should be 2 distinct entities and that atherosclerosis, not embolism, might be the main cause of deep ESUS.

Cerebral embolic protection and severity of stroke following transcatheter aortic valve replacement.

BACKGROUND: The cerebral embolic protection (CEP) device captures embolic debris during transcatheter aortic valve replacement (TAVR). However, the impact of CEP on stroke severity following TAVR remains unclear. Therefore, we aimed to examine whether CEP was associated with reduced severity of stroke following TAVR. METHODS: This was a retrospective cohort study of 2839 consecutive patients (mean age: 79.2 ± 9.5 years, females: 41.5%) who underwent transfemoral TAVR at our institution between 2013 and 2020. We categorized patients into Sentinel CEP users and nonusers. Neuroimaging data were reviewed and the final diagnosis of a cerebrovascular event was adjudicated by a neurologist blinded to the CEP use or nonuse. We compared the incidence and severity (assessed by the National Institutes of Health Stroke Scale [NIHSS]) of stroke through 72 h post-TAVR or discharge between the two groups using stabilized inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: Of the eligible patients, 1802 (63.5%) received CEP during TAVR and 1037 (36.5%) did not. After adjustment for patient characteristics by stabilized IPTW, the rate of overall stroke was numerically lower in CEP users than in CEP nonusers, but the difference did not reach statistical significance (0.49% vs. 1.18%, p = 0.064). However, CEP users had significantly lower rates of moderate-or-severe stroke (NIHSS ≥ 6: 0.11% vs. 0.69%, p = 0.013) and severe stroke (NIHSS ≥ 15: 0% vs. 0.29%, p = 0.046). Stroke following CEP use (n = 8), compared with stroke following CEP nonuse (n = 15), tended to carry a lower NIHSS (median [IQR], 4.0 [2.0-7.0] vs. 7.0 [4.5-19.0], p = 0.087). Four (26.7%) out of 15 patients with stroke following CEP nonuse died within 30 days, with no death after stroke following CEP use. CONCLUSIONS: CEP use may be associated with attenuated severity of stroke despite no significant difference in overall stroke incidence compared with CEP nonuse. This finding is considered hypothesis-generating and needs to be confirmed in large prospective studies.

Utility of P-wave abnormalities for distinguishing embolic stroke from non-embolic stroke.

BACKGROUND: Our aim was to analyze the incidence of P-wave abnormalities in embolic and non-embolic strokes, and evaluate its clinical usefulness for predicting stroke etiology. METHODS: We included 376 consecutive patients hospitalized for acute ischemic stroke from January 2015 to September 2021. Among the patients in sinus rhythm at admission, 31 had ischemic stroke due to atrial fibrillation (AF)-related embolism, 59 had embolic stroke of unknown source (ESUS), and 143 had non-embolic stroke. P-wave abnormalities were defined as 1. P-wave axis abnormality (PWAA); 2. P-wave terminal force in V1 (PTFV1) ≤ -4000 µV*ms; 3. advanced inter-atrial block (A-IAB). RESULTS: The prevalence of each type of abnormality was consistently lower in patients with non-embolic stroke than in those with AF-related embolism (AF-related vs. ESUS vs. non-embolic; PWAA, 45% vs. 20% vs. 14%; PTFV1, 36% vs. 37% vs. 15%; and A-IAB, 55% vs. 31% vs. 13%, respectively). The identification of at least one type of P-wave abnormality improved the sensitivity compared to using a single abnormality parameter (sensitivity 72%, specificity 62%), while at least two types of abnormality had low sensitivity, but high specificity (sensitivity 29%, specificity 95%). Multivariate regression analysis revealed that identification of at least one type of P-wave abnormality was independently associated with embolic stroke (odds ratio 3.11, 95%CI 1.46-6.63). CONCLUSIONS: The incidence of each type of P-wave abnormality was significantly lower in patients with non-embolic stroke. A combination of PWAA, PTFV1, and A-IAB parameters could be useful for distinguishing embolic from non-embolic stroke.

Characteristics of non-stenotic carotid plaque in embolic stroke of undetermined source compared with cardiogenic embolism: a retrospective cross-sectional observational study.

BACKGROUND: Non-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS. METHODS: This is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People's Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS. RESULTS: We had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45-12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55-16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727-0.896; p < 0.001). CONCLUSION: Our results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.

Age Alters Prevalence of Left Atrial Enlargement and Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source.

BACKGROUND: Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population. METHODS: A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions. RESULTS: Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54-74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1-4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P<0.01), diabetes (41.0% versus 25.6%, P=0.01), dyslipidemia (56.4% versus 40.0%, P=0.01), and coronary artery disease (22.8% versus 11.3%, P=0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0-3] versus 1.5 mm [IQR 0-2.6], P<0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0-2.9] versus 1.5 mm [IQR 0-2.5], P<0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54, P=0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P=0.02). CONCLUSIONS: Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.

Stroke events after transcatheter aortic valve implantation: Temporal relationships and affected brain regions.

BACKGROUND: Despite continuous improvements in transcatheter aortic valve implantation (TAVI), periprocedural strokes remain a devastating complication. Randomized controlled trials failed to demonstrate a reduction in clinically apparent strokes or mortality after TAVI due to cerebral embolic protection (CEP). To identify potential targets of CEP strategies during TAVI, we evaluated affected brain regions, and temporal patterns of stroke onset in a routine clinical sample. METHODS AND RESULTS: A total of 3,164 consecutive patients treated with TAVI from 2008 to 2019 at a single center were screened for cerebrovascular events. Affected cerebral regions were determined according to clinical symptoms and brain imaging. Rates of disabling stroke and non-disabling stroke at 30 days were 2.2% and 1.4%, respectively. The frequency of all strokes decreased from 5.0% to 3.0% over time (P = .012). Patients with impaired left-ventricular function (OR 2.19), increased CHA2DS2-VASc (OR 1.39) and moderate/severe spontaneous echo contrast (OR 3.60) had a higher stroke risk. Acute symptom onset occurred during TAVI (19.4%), within 24 hours (40.3%) or later (25.0%); 98.3% of strokes were of ischemic origin. In intraprocedural strokes, 53.2% of lesions were found in locations considered protected by current CEP devices, and 37.5% of patients with intraprocedural strokes were exclusively affected in these areas. Baseline or procedural parameters were not associated with embolic distribution patterns. CONCLUSIONS: Most strokes occurred early after TAVI - but not necessarily during the procedure - and affected multiple brain regions only partially protected by current CEP devices. Efficient prevention of cerebrovascular events may require strategies beyond the TAVI procedure to minimize stroke risk and additional randomized controlled trials will be required to clarify the role of CEP in efficient stroke prevention during TAVI.