Enhancing Stroke Prevention in Transcatheter Aortic Valve Replacement: The Role of F2, a Novel Neuroprotection Device.

Background: Transcatheter aortic valve replacement (TAVR) is an established treatment for severe aortic stenosis, yet cerebrovascular complications such as stroke and transient ischemic attacks (TIA) remain significant concerns. Cerebral embolic protection (CEP) devices have emerged to mitigate these risks, but their efficacy remains debated. We aimed to evaluate the impact of CEP device use on cerebrovascular and mortality outcomes during TAVR using real-world data. Methods: This retrospective cohort analysis was conducted using TriNetX, a large federated health research network, capturing data from 68 healthcare organizations across the U.S. Patients undergoing TAVR with (Cohort 1) and without (Cohort 2) cerebral embolic protection devices were identified using ICD-10-PCS procedural codes. Outcomes evaluated included all-cause mortality, stroke, and TIA within one year post-procedure. Propensity score matching (1:1) was performed to balance cohorts on key variables, including age, sex, and race. Risk differences, odds ratios, and 95% confidence intervals (CIs) were calculated. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used for mortality and cerebrovascular outcomes. Results: Following matching, each cohort comprised 25 patients. Baseline demographics were similar: mean age 82 vs. 81 years, 44% female in both groups. Mortality risk was identical in both groups (40% vs. 40%; risk difference 0.0, 95% CI [-0.272, 0.272]; p=1.00). TIA risk was also comparable (40% vs. 40%; risk difference 0.0, 95% CI [-0.272, 0.272]; p=1.00). However, the group with cerebral embolic protection demonstrated a significantly lower incidence of stroke (0% vs. 40%; risk difference -0.400, 95% CI [-0.592, -0.208]; p=0.000), indicating a potential protective benefit. Conclusions: This analysis suggests that the use of a cerebral embolic protection device during TAVR is associated with a significant reduction in stroke risk without impacting all-cause mortality or TIA risk. These findings support the selective use of cerebral embolic protection devices during TAVR to potentially reduce stroke risk. However, the small matched cohort size limits the generalizability of these results, and larger studies are warranted to validate these findings, assess cost-effectiveness, and refine patient selection criteria for optimal clinical outcomes.

Introduction although transcatheter aortic valve replacement (TAVR) represents a milestone in the treatment of degenerative aortic stenosis, stroke remains an important complication compared to surgical aortic valve replacement (SAVR). Multiple magnetic resonance imaging (MRI) studies demonstrated a substantial rate of new cerebral ischemic lesions after TAVR. In order to avoid debris passage into the circulation and to prevent procedure-related embolic stroke, cerebral embolic protection (CEP) devices were developed. However, their safety and efficacy remain controversial. Very recently, new studies provided additional evidence on this topic. Aim to assess the entire body of evidence from randomized controlled studies about neurological outcomes after TAVR. Materials and Methods a systematic meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, Scopus, and Google Scholar for randomized controlled studies. The following keywords were used for the search: “transcatheter aortic valve implantation” or “stroke prevention” or “embolic protection” and “cerebral protection”. Study groups were defined as a the “CEP group” and the “control group”. Non-randomized studies reporting outcomes with cerebral embolic protection (CEP) during TAVR were excluded to reduce the selection and confounding bias of observational pilot studies. The primary outcome was post-procedural stroke. Secondary outcomes included total lesion volume on MRI and new ischemic lesions on MRI. Results nine trials including 4077 patients were eligible for analysis and included to the meta-analysis. Of those, 2203 patients were randomized to cerebral embolic protection and 1874 patients to control group. Despite the rate of post-procedural stroke was higher in the CEP arm (2.27%) compared to the control arm (2.87%, p<0.001), the use of cerebral embolic protection was not associated with a significantly lower risk of stroke (OR=0.82, 95% CI 0.59-1.15; p=0.255). Cumulative meta-analysis revealed a trend towards a lower impact on stroke prevention with more recent trials. Conclusions use of cerebral embolic protection devices during TAVR is a safe procedure. However, the current outline of results from all randomized controlled trials available does not support its routine use, as no significant reduction of stroke risk was evident. The use of these devices might be considered in selected high-risk patients, such as in the setting of heavy calcified cusps or atherosclerotic aortic lesions.

Judgment Reserved: The Evolving Development of Cerebral Embolic Protection Devices in Transcutaneous Aortic Valve Replacement

Introduction: Patients undergoing Transcatheter Aortic Valve Replacement/Implantation (TAVR/TAVI) are at risk of periprocedural cerebrovascular events. Cerebral Embolic Protection (CEP) devices have been developed to reduce the incidence of stroke and improve short-term outcomes in this population. This meta-analysis aimed to evaluate the safety and efficacy of CEP devices in patients undergoing TAVR/TAVI. Methods: A comprehensive literature search was conducted using PubMed, Cochrane Library, and ClinicalTrials.gov to identify relevant randomized controlled trials using keywords like “Transcatheter aortic valve replacement” or “Transcatheter aortic valve implantation” and “Cerebral Embolic Protection device”. After screening and eligibility assessment, 6 articles were included from an initial pool of 157 records. Meta-analysis was performed using RevMan 5.4 software. Quality assessment was performed using the Cochrane Risk of Bias tool. Results: Final analysis included 11,600 patients to investigate the relative effect of CEP devices versus no protection on different efficacy and safety outcomes in patients undergoing TAVR/TAVI. The pooled analysis demonstrated a non-significant reduction in the risk of stroke within 30 days in the CEP group compared to the control group (RR=0.81; 95% CI 0.61 to 1.07; p=0.14, I2 =14%). The use of CEP was not associated with a significant difference in all-cause mortality (RR=0.89; 95% CI 0.50 to 1.58; p=0.68, I2=18%), disabling stroke (RR=0.53; 95% CI 0.26 to 1.07; p=0.08, I2=44%) and non-disabling stroke (RR=0.92; 95% CI 0.61 to 1.39; p=0.69, I2=0%) within 30 days. Safety outcomes showed no significant differences between CEP and control groups in terms of major vascular complications (RR=0.98; 95% CI 054 to 1.77; p=0.95, I2 =50%), major or life-threatening bleeding (RR=0.67; 95% CI 0.26 to 1.78; p=0.43, I2 =64%), and acute kidney injury (RR=1.16; 95% CI 0.92 to 1.47; p=0.20, I2=0%). Discussion: CEP devices may reduce the risk of disabling stroke in patients undergoing TAVR/TAVI; however, the reduction did not reach statistical significance. Additionally, there was no significant benefit observed in all-cause mortality or other efficacy and safety outcomes. These findings highlight the need for larger, high-quality trials to better clarify the clinical value of CEP devices in this setting.

Transcatheter aortic valve replacement (TAVR) has become a first-line treatment for severe aortic stenosis with intermediate to high-risk population with its use increasingly expanding into younger and low-risk cohorts as well. Cerebrovascular events are one of the most serious consequential complications of TAVR, which increase morbidity and mortality. The most probable origin of such neurological events is embolic in nature and the majority occur in the acute phase after TAVR when embolic events are most frequent. Cerebral embolic protection devices have been designed to capture or deflect these emboli, reducing the risk of peri-procedural ischaemic events. They also carry the potential to diminish the burden of new silent ischemic lesions during TAVR. Our review explores different types of these device systems, their rationale, and the established clinical data.

Transcatheter aortic valve replacement (TAVR) is a newer alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis. Clinical trials have investigated TAVR's safety and effectiveness. Cerebral embolization is a common complication leading to stroke after TAVR and SAVR; different cerebral protection methods have been studied to prevent this.This paper evaluates the rate of post-procedural stroke rates between TAVR and SAVR and investigates the effect of cerebral protective methods on the stroke risk post-TAVR.Publications on TAVR and SAVR were found using specific criteria on PubMed. The Placement of Aortic Transcatheter Valves 1 (PARTNER 1) and PARTNER 2, the Nordic Aortic Valve Intervention (NOTION), and Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trials compared the incidence of complications between TAVR and SAVR. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCED), CoreValve (Medtronic, Minneapolis, MN), Neurologic Complications of Unprotected Transcatheter Aortic Valve Implantation (Neuro-TAVI), Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LotusTM Valve System (Boston Scientific, Marlborough, MA) - Randomized Clinical Evaluation (REPRISE II), and The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STC/ACC TVT) registry studies further explored the risk of stroke in TAVR. The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVO)-3 MRI, a prospective randomized evaluation of the TriGuardTM HDH (Keystone Heart, Tampa, FL) Embolic Deflection Device During Transcatheter Aortic Valve Replacement (DEFLECT III), Claret Embolic Protection and Transcatheter Aortic Valve Implantation (CLEAN-TAVI), and Cerebral Protection in Transcatheter Aortic Valve Replacement (SENTINEL) trials investigated cerebral protection methods post-TAVR for stroke prevention.In the PARTNER 1 trial, the stroke rate was greater in the TAVR group than in the SAVR group at one year (8.3% vs. 4.3%, P=0.04); the PARTNER 2 trial showed a lower risk of stroke at two years (6.2% and 6.4%, respectively). The NOTION and SURTAVI trials showed no significant difference in stroke rate between TAVR and SAVR at one year (13.1% vs 16.3%, respectively; p = 0.43). An increase in stroke rate after TAVR was found in the ADVANCED trial (5.6% at 31 days - two years) and CoreValve trial (4.3% in the late phase). The Neuro-TAVI trial showed ischemia after TAVR in 20% of patients at discharge. In the STC/ACC TVT Registry, the rate of post-procedure disabling stroke was 1.7% at 30 days. Finally, the BRAVO-3 MRI study showed no advantages between bivalirudin or unfractionated heparin in preventing cerebral lesion formation (65.5% vs 58.1%, respectively; p = 0.55). The DEFLECT III, CLEAN-TAVI, and SENTINEL trials assessed the safety and efficacy of transcatheter cerebral embolic protection devices (CEPDs); their results ranged from 50% improvement (CLEAN-TAVI) to none (DEFLECT III, SENTINEL), therefore, showing non-inferiority of cerebral embolic protection devices for TAVR patients.The clinical trials studied in this paper showed a similar incidence of stroke in both groups, with the majority of TAVR patients developing cerebral lesions. With the addition of cerebral embolic protective devices, this incidence has decreased.

Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited. We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights. Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 [95% CI, 0.68-1.13]; absolute risk difference, -0.15% [95% CI, -0.49 to 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]; absolute risk difference, -0.28% [95% CI, -0.52 to -0.03]). Results were generally consistent across the secondary end points, as well as subgroup analyses. In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.

First-in-Man Study Evaluating the Emblok Embolic Protection System During Transcatheter Aortic Valve Replacement

Cerebral embolic protection devices (EPDs) were developed to mitigate the risk of stroke during transcatheter aortic valve replacement (TAVR), but their benefit remains unproven. In the PROTECTED-TAVR trial (Stroke Protection With Sentinel During Transcatheter), EPD use did not reduce periprocedural stroke (primary study outcome) but led to a 62% reduction in the secondary end point of disabling stroke. Given these results, the impact of EPDs during TAVR remains unclear. We used STS/ACC TVT registry data to examine the association between EPD use and a proxy for disabling stroke among transfemoral TAVR patients between January 2018 and June 2023. The primary outcome was in-hospital disabling stroke-defined as stroke associated with either in-hospital death or discharge to a nonhome location. We evaluated the association between EPD use and disabling stroke using instrumental variable analysis with a site-level preference for EPD use as the instrument-a quasi-experimental approach that can support causal inference. In addition, we performed a propensity score-based comparison using overlap weighting as a secondary analysis. The study population consisted of 414 649 patients of whom 53 389 (12.9%) received an EPD. The unadjusted rate of in-hospital disabling stroke was 0.7% among the EPD group and 0.9% in the no-EPD group. EPD use was associated with a reduction in disabling stroke in both instrumental variable analysis (relative risk, 0.87 [95% CI, 0.73-1.00]) and propensity-weighted analysis (odds ratio, 0.79 [95% CI, 0.70-0.90]) but was not associated with a reduction in nondisabling stroke. In subgroup analyses, the benefit of EPD was greater among those with versus without prior stroke (Pinteraction<0.05 for both instrumental variable and propensity-weighted analyses). In the largest study to date, among patients undergoing TAVR, EPD use was associated with a small, borderline significant reduction in stroke associated with death or discharge to a nonhome location (a proxy for disabling stroke) that is likely to be causal in nature. Taken together with previous mechanistic and clinical studies, these findings provide credible evidence that EPDs benefit patients undergoing TAVR.

We describe the first-in-human experience with a novel cerebral embolic protection device used during transcatheter aortic valve implantation (TAVI). One current challenge of TAVI is the reduction of procedural stroke. Procedural mobilisation of debris is a known source of cerebral embolisation. Mechanical protection by transient filtration of cerebral blood flow might reduce the embolic burden during TAVI. We aimed to evaluate the feasibility and safety of the Claret CE Pro™ cerebral protection device in patients undergoing TAVI. Patients scheduled for TAVI were prospectively enrolled at three centres. The Claret CE Pro™ (Claret Medical, Inc. Santa Rosa, CA, USA) cerebral protection device was placed via the right radial/brachial artery prior to TAVI and was removed after the procedure. The primary endpoint was technical success rate. Secondary endpoints encompassed procedural and 30-day stroke rates, as well as device-related complications. Deployment of the Claret CE Pro™ cerebral protection device was intended for use in 40 patients, 35 devices were implanted into the aortic arch. Technical success rate with delivery of the proximal and distal filter was 60% for the first generation device and 87% for the second-generation device. Delivery times for the first-generation device were 12.4±12.1 minutes and 4.4 ± 2.5 minutes for the second-generation device (p<0.05). The quantity of contrast used related to the Claret CE Pro System was 19.6 ± 3.8 ml. Captured debris was documented in at least 19 of 35 implanted devices (54.3%). No procedural transient ischaemic attacks, minor strokes or major strokes occurred. Thirty-day follow-up showed one minor stroke occurring 30 days after the procedure, and two major strokes both occurring well after the patient had completed TAVI. The use of the Claret CE Pro™ system is feasible and safe. Capture of debris in more than half of the patients provides evidence for the potential to reduce the procedural cerebral embolic burden utilising this dedicated filter system during TAVI.

Background: Stroke is a devastating complication of transcatheter aortic valve replacement (TAVR). Cerebral embolic protection devices (CEPD) have been introduced to reduce TAVR-related stroke by capturing or deflecting debris during the procedure. While these devices can capture embolic material, their clinical benefit in preventing stroke remains uncertain. We aimed to determine whether the use of CEPD during TAVR reduces the incidence of periprocedural stroke. Methods: We performed a systematic review and meta-analysis of studies comparing TAVR with versus without CEPD. We searched PubMed, Embase, and ClinicalTrials.gov for RCTs (randomized controlled trials) comparing CEPDs to no protection in TAVR patients from 2011 to May 2025. Nine RCTs involving a total of 11,608 patients (CEPD group n=5,953; control n=5,655) were included. Stroke outcomes were defined according to Valve Academic Research Consortium-2 (VARC-2) criteria and categorized as- all stroke, disabling stroke, or non-disabling stroke. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. Heterogeneity also was measured. Results: Stroke rates were low and did not differ significantly between the CEPD (n=343) and control (n=319) groups. The incidence of all strokes was 1.96% with CEPD vs 1.88% without CEPD (RR 0.97, 95% CI 0.75–1.15; p=0.50). Disabling stroke occurred in 0.79% of CEPD patients vs 0.95% of controls (RR 0.79, 95% CI 0.57-1.10; p=0.16). Non-disabling stroke occurred in 1.26% of patients in both groups (RR 1.06, 95% CI 0.8 -1.40; p=0.64). There was no significant heterogeneity across trials is (0) for all endpoints. Notably, the largest trial in the analysis (BHF PROTECT-TAVI, n=7,635) showed no difference in stroke rates with CEPD, aligning with the overall results. Subgroup analyses revealed a trend toward fewer disabling strokes with CEPD use, but this trend was not statistically significant. Conclusion: We found no significant stroke risk reduction with the use of CEPDs during TAVR. While a trend toward fewer disabling strokes was observed, it was not statistically significant. Routine use of CEPDs is not supported, and selective use in high-risk patients warrants further large RCTs.

Trends in Cerebral Embolic Protection Device Use and Association With Stroke Following Transcatheter Aortic Valve Implantation

Stroke represents the most feared complication of transcatheter aortic valve implantation (TAVI). Although device innovation, operator experience, and better patient selection have been associated with a progressive reduction of stroke rates, its occurrence has a relevant impact on morbidity and mortality after TAVI. Embolization of material during manipulation of catheters, wires, and devices within the aortic arch is the main mechanism of periprocedural thromboembolic cerebrovascular events (CVE). In order to prevent this phenomenon, several cerebral embolic protection devices (EPDs) have been studied in patients undergoing TAVI. These devices are intended to deflect or filter emboli and protect cerebral circulation. A multitude of studies showed the safety and feasibility of their use. The rationale for their use is further supported by the observation that debris can be found in up to 99% of patients, at the end of the procedure. However, although cerebral protection has been associated with a reduction of silent cerebral ischemic lesions identified by diffusion-weighted magnetic resonance imaging (DW-MRI), their impact on stroke risk and neurocognitive status after TAVI is still not clear. Intrinsic limitations of studies so far performed as well as the lack of standardization for definition of neurological endpoints challenge the interpretation of currently available evidence, and further studies are needed to define the role of EPDs in TAVI populations.

Introduction Stroke is a feared complication in patients undergoing transcatheter aortic valve implantation (TAVI), affecting up to 2.3% of patients in contemporary series. Cerebral embolic protection devices (CEPD) are designed to prevent embolization of debris during the procedure. Current evidence from randomized clinical trials (RCTs) and adjusted observational studies is controversial. Purpose Study the influence of CEPD on stroke, mortality, silent ischemic lesions and neurocognitive function. Methods A systematic search was conducted of the Cochrane Library, EMBASE, MEDLINE, Web of Science and conference abstracts in any language from database conception until March 2nd 2021 including RCTs or observational studies with propensity score (PS) adjustment comparing TAVI with or without the use of CEPD. Estimates for clinical outcomes (30-day stroke, death and composite) were combined using a random-effects meta-analysis using the Inverse of Variance method to determine the pooled odds ratio (OR) of CEPD compared with non-CEPD. For neurocognitive function assessment, results were pooled to obtain the relative risk (RR) using the Mantel-Haenzel method. Finally, continuous outcomes from the MRI cerebral evaluation were combined in a random-effects model with standardized mean difference (SMD) between EPD and non-EPD. Results Twelve studies were eligible (n=165,315), six RCTs and six observational studies with PS adjustment. Median age of the patients was 80.8 (IQR=80–81.84) in patients with CEPD and 80.92 (IQR=79.75–82.15) in non-CEPD. Previous stroke or transient ischemic attack was 588/25,056 in CEPD and 673/25,583 in non-CEPD. STS-PROM score was 5.6% (IQR=4.64–6.2) for CEPD and 6.41% (IQR=4.72–6.9) for non-CEPD. Pooled analysis detected no-significant differences between CEPD and non-CEPD (OR=0.74; 95% CI 0.52–1.06; P=0.101; I2=82.6%) for 30-day Stroke but a significant difference favoring CEPD (OR=0.75; 95% CI 0.68–0.82; P&amp;lt;0.000; I2=0%) for 30-day mortality (Figure 1). Regarding cerebral DW-MRI assessment and neurocognitive function evaluation, we observed no significant differences between groups (Figure 2) Conclusion In the present metanalysis of six RCTs and six PS adjusted observational studies, the use of a CEPD during TAVI was associated with a lower risk in 30-day mortality. We found no statistical difference between TAVI with or without CEPD for 30-day stroke, total lesion volume per patient, number of ischemic lesions per patient and neurocognitive function assessments. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Spanish Society for Cardiovascular and Endovascular Surgery Figure 1. A) Inverse variance random- effects OR and 95% CI for 30- day stroke stratified by study design. B) Inverse variance random- effects OR and 95% CI for 30- day mortality stratified by study design.Figure 2. Overall effect estimates (SMD and RR with 95% CI, p- values and heterogeneity) for secondary outcomes.

Cerebral embolic protection device utilization and outcomes in transcatheter aortic valve replacement: A nationally representative propensity matched analysis