Role of Cerebral Embolic Protection Devices in Patients Undergoing Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis.

BACKGROUND: Cerebral embolic protection devices (CEPD) capture embolic material in an attempt to reduce ischemic brain injury during transcatheter aortic valve replacement. Prior reports have indicated mixed results regarding the benefits of these devices. With new data emerging, we performed an updated meta-analysis examining the effect of CEPD during transcatheter aortic valve replacement on various clinical, neurological, and safety parameters. METHODS AND RESULTS: A comprehensive review of electronic databases was performed comparing CEPD and no-CEPD in transcatheter aortic valve replacement. Primary clinical outcome was all-cause stroke. Secondary clinical outcomes were disabling stroke and all-cause mortality. Neurological outcomes included worsening of the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score from baseline at discharge, presence of new ischemic lesions, and total lesion volume on neuroimaging. Safety outcomes included major or minor vascular complications and stage 2 or 3 acute kidney injury. Seven randomized controlled trials with 4016 patients met the inclusion criteria. There was no statistically significant difference in the primary clinical outcome of all-cause stroke; secondary clinical outcomes of disabling stroke, all-cause mortality, neurological outcomes of National Institutes of Health Stroke Scale score worsening, Montreal Cognitive Assessment worsening, presence of new ischemic lesions, or total lesion volume on diffusion-weighted magnetic resonance imaging between CEPD versus control groups. There was no statistically significant difference in major or minor vascular complications or stage 2 or 3 acute kidney injury between the groups. CONCLUSIONS: The use of CEPD in transcatheter aortic valve replacement was not associated with a statistically significant reduction in the risk of clinical, neurological, and safety outcomes.

Midterm follow-up after computed tomography angiography planned left atrial appendage closure.

BACKGROUND: While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™ legacy and FLX devices, there has been no reported long-term data for this approach. OBJECTIVES: We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device. METHODS: A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively. RESULTS: From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively. CONCLUSIONS: CTA-based preprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years.

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.

First-in-human study of the CAPTIS embolic protection system during transcatheter aortic valve replacement.

BACKGROUND: Stroke and other clinically significant embolic complications are well documented in the early period following transcatheter aortic valve replacement (TAVR). The CAPTIS device is an embolic protection system, designed to provide neurovascular and systemic protection by deflecting debris away from the brain's circulation, capturing the debris and thus avoiding systemic embolisation. AIMS: We aimed to study the safety and feasibility study of the CAPTIS complete cerebral and full-body embolic protection system during TAVR. METHODS: A first-in-human study investigated the safety, feasibility and debris capturing ability of CAPTIS during TAVR. Patients were followed for 30 days. The primary endpoints were device safety and cerebrovascular events at 72 hours. RESULTS: Twenty patients underwent TAVR using balloon-expandable or self-expanding valve systems. CAPTIS was successfully delivered, positioned, deployed, and retrieved in all cases, and TAVR was successfully completed without device-related complications. No cerebrovascular events were observed. High numbers of debris particles were captured in all patients. CONCLUSIONS: The use of the CAPTIS full-body embolic protection system during TAVR was safe, and it captured a substantial number of debris particles. No patient suffered from a cerebrovascular event. A randomised clinical trial is warranted to prove its efficacy.

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.

Cerebral embolic protection during transcatheter heart interventions.

Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), with the incidence of clinically apparent stroke seemingly fixed at around 3% despite TAVR's significant evolution during the past decade. Embolic showers of debris (calcium, atheroma, valve material, foreign material) are captured in the majority of patients who have TAVR using a filter-based cerebral embolic protection device (CEPD). Additionally, in systematic brain imaging studies, the majority of patients receiving TAVR exhibit new cerebral lesions. Mechanistic studies have shown reductions in the volume of new cerebral lesions using CEPDs, yet the first randomised trial powered for periprocedural stroke within 72 hours of a transfemoral TAVR failed to meet its primary endpoint of showing superiority of the SENTINEL CEPD. The present review summarises the clinicopathological rationale for the development of CEPDs, the evidence behind these devices to date and the emerging recognition of cerebral embolisation in many non-TAVR transcatheter procedures. Given the uniqueness of each of the various CEPDs under development, specific trials tailored to their designs will need to be undertaken to broaden the CEPD field, in addition to evaluating the role of CEPD in non-TAVR transcatheter heart interventions. Importantly, the cost-effectiveness of these devices will require assessment to broaden the adoption of CEPDs globally.

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.

Cerebral embolic protection during transcatheter aortic valve replacement: a systematic review and meta-analysis of propensity score matched and randomized controlled trials using the Sentinel cerebral embolic protection device.

BACKGROUND: The Sentinel cerebral embolic protection device (CEP) aims to reduce the risk of stroke during transcatheter aortic valve replacement (TAVR). We performed a systematic review and meta-analysis of propensity score matched (PSM) and randomized controlled trials (RCT) investigating the effect of the Sentinel CEP to prevent strokes during TAVR. METHODS: Eligible trials were searched through PubMed, ISI Web of science databases, Cochrane database, and proceedings of major congresses. Primary outcome was stroke. Secondary outcomes included all-cause mortality, major or life-threatening bleeding, major vascular complications and acute kidney injury at discharge. Fixed and random effect models were used to calculate the pooled risk ratio (RR) with 95% confidence intervals (CI) and absolute risk difference (ARD). RESULTS: A total of 4066 patients from 4 RCTs (3'506 patients) and 1 PSM study (560 patients) were included. Use of Sentinel CEP was successful in 92% of patients and was associated with a significantly lower risk of stroke (RR: 0.67, 95% CI: 0.48-0.95, p = 0.02. ARD: -1.3%, 95% CI: -2.3 - -0.2, p = 0.02, number needed to treat (NNT) = 77), and a reduced risk of disabling stroke (RR: 0.33, 95% CI: 0.17-0.65. ARD: -0.9%, 95% CI: -1.5 - -0.3, p = 0.004, NNT = 111). Use of Sentinel CEP was associated with a lower risk of major or life-threatening bleeding (RR: 0.37, 95% CI: 0.16-0.87, p = 0.02). Risk for nondisabling stroke (RR: 0.93, 95% CI: 0.62-1.40, p = 0.73), all-cause mortality (RR: 0.70, 95% CI: 0.35-1.40, p = 0.31), major vascular complications (RR: 0.74, 95% CI: 0.33-1.67, p = 0.47) and acute kidney injury (RR: 0.74, 95% CI: 0.37-1.50, p = 0.40) were similar. CONCLUSIONS: The use of CEP during TAVR was associated with lower risks of any stroke and disabling stroke with an NNT of 77 and 111, respectively.

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.

Dual-layered stents reduce cerebral embolism compared with first-generation stents during carotid stenting of high lipid core plaque lesions.

BACKGROUND: Periprocedural lipid core plaque (LCP) has been detected in carotid arteries assessed by catheter-based near-infrared spectroscopy (NIRS). High LCP is associated with cerebral embolism after carotid artery stenting (CAS) using a first-generation stent. We aimed to evaluate whether dual-layered stents reduce embolic infarcts in patients with high LCP and change of lipid signal as assessed by NIRS during CAS. METHODS: Participants comprised 210 consecutive patients undergoing CAS. The study was divided into two distinct periods, with first-generation closed-cell stents used in the earlier period and dual-layered stents used in the later period. NIRS was performed at baseline, after stent implantation, and after balloon post-dilatation to analyze maximal lipid core burden index at minimal luminal area (max-LCBIMLA). RESULTS: The ipsilateral cerebral embolism rate was significantly lower with dual-layered stents (9%) than with first-generation stents (33%, p<0.001), particularly with highly lipidic lesions (12% vs 60%, p<0.001). On multivariate logistic regression analysis, high LCP and first-generation stent usage were factors related to ipsilateral cerebral embolism (both p<0.001; OR 8.28 (95% CI 3.49 to 19.64) and OR 8.07 (95% CI 2.33 to 27.93), respectively). Max-LCBIMLA decreased significantly after stenting in both groups (both p<0.01) and max-LCBIMLA after balloon post-dilatation was significantly lower with dual-layered stents (22.4±65.6) than with first-generation stents (124.2±208.2; p=0.006). CONCLUSIONS: Dual-layered stents reduce embolic infarcts in patients with highly lipidic plaque lesions as assessed by NIRS who undergo CAS. Dual-layered stents significantly reduced NIRS-derived lipid signals after stenting.

Clinical Outcome of Transcatheter Aortic Valve Replacement With TriGUARD 3™ Cerebral Embolic Protection Device.

OBJECTIVE: Periprocedural stroke during transcatheter aortic valve replacement (TAVR) is a highly feared adverse event. The TriGUARD 3 cerebral embolic protection device (CEPD) may have the potential benefit of reduction of embolic events, but it still remains unclear whether it reduces the incidence of periprocedural stroke or transient ischemic attack (TIA). We aimed to investigate whether the latest TriGUARD 3 CEPD reduces the incidence of clinically overt stroke within 72 h or at discharge after TAVR. METHODS: In this prospective single-center study 117 patients (mean age 80.3 years, 53.8 % male) were included from July 2020 to December 2021. RESULTS: The primary efficacy endpoint of this study, periprocedural clinically overt stroke or TIA, within 72 h or at discharge after TAVR with the TriGUARD 3 CEPD occurred in 1/117 pts (0.8 %). Secondary endpoints (device related issues such as life-threatening or disabling bleeding, acute kidney injury, major vascular complications) were reported in 4/117 pts (3.4 %). CONCLUSIONS: This study suggests that the use of the latest TriGUARD 3™ CEPD in transfemoral TAVR seems to be associated with a low rate of clinically overt stroke and a low rate of device related adverse events, reflecting "real world" TAVR practice. However these results should be hypothesis generating and confirmed in a large RCT.

A Bibliometric Analysis of Cardioembolic Stroke From 2012 to 2022.

Cardioembolic stroke, a subtype of ischemic stroke with the worst prognosis, is quietly threatening public health. We aimed to visualize the development trend and hotspots of research on cardioembolic stroke. A total of 2886 papers about cardioembolic stroke published from 2012 to 2022 were retrieved in the Web of Science Core Collection (WoSCC) database. Further, we performed a bibliometric analysis of these publications, such as generating cooperation maps, co-citation analysis of journals and references, and cluster analysis of keywords. According to the results, cardioembolic stroke research faces many clinical challenges. We obtained the knowledge maps of countries/institutions, authors, journals with high publications and citations, and representative references in this field. Studies about optimal prevention strategies for cardioembolic stroke, identification of cardioembolism in cryptogenic stroke, and prophylactic anticoagulation for patients with embolic stroke of undetermined source (ESUS) or at high risk of left ventricle (LV) thrombus are in the spotlight.

Embolic Stroke of Undetermined Source: Current Perspectives on Diagnosis, Investigations, and Management.

In 2014, Hart et al. introduced the concept of "embolic stroke of undetermined source" (ESUS) to the clinical-research stroke community. The hypothesis underlying the development of the ESUS construct was that this potentially heterogenous group of stroke mechanisms were largely thromboembolic, and would thus benefit from anticoagulation over antiplatelet for secondary prevention. Since then, 2 large clinical trials have shown that, to date, there is not a clear uniform antithrombotic strategy for secondary prevention after ESUS as it was originally broadly defined. However, this work has yielded valuable information about the patient phenotypes that experience ESUS strokes, as well as hypothesis-generating substudies that have given rise to the next generation of secondary prevention trials aimed at more personalized approaches for different suspected mechanisms of embolic stroke. In parallel with the evolution of ESUS, several studies aimed at screening for atrial fibrillation in the secondary stroke prevention population have generated additional questions about the mechanistic relevance of atrial fibrillation detected after stroke, and how this should inform poststroke workup, and secondary prevention strategies. Herein, we provide a synthesis of the current understanding surrounding the patient phenotypes that experience ESUS strokes, and previous, ongoing, and anticipated clinical trials that will guide earlier and later secondary prevention strategies and poststroke cardiac investigations.

[Modified classification, screening, prevention and treatment of cardioembolic stroke].

Ischemic stroke is usually regarded as a neurological disease, but cardiogenic cerebral embolism is actually one of the most common identifiable causes of ischemic stroke. According to the origin of embolus (left heart/right heart system) and related structural abnormalities, this article expanded and refined the classification definition of cardiogenic cerebral embolism, and proposed an improved classification method of ischemic stroke (PUMCH-ISC). In addition, this article gave a practical clinical screening program for cardiovascular physicians according to different causes of stroke, and sorted out the prevention and treatment strategies and progress of common causes of cardiogenic cerebral embolism, aiming to help cardiovascular physicians and neurologists improve the screening, diagnosis and accurate prevention and treatment of cardiogenic cerebral embolism.