Characterization of Cerebral Embolic Capture Using the SENTINEL Device During Transcatheter Aortic Valve Implantation in Low to Intermediate-Risk Patients: The SENTINEL-LIR Study

ndications for transcatheter aortic valve replacement (TAVR) have expanded to aortic stenosis patients with low- and intermediate-risk of surgery. 1 Post-TAVR stroke causes acute and long-term morbidity and mortality. The stroke rate 30 days after TAVR was reported as 3.4% in low-risk patients. Prior

I ndications for transcatheter aortic valve replacement (TAVR) have expanded to aortic stenosis patients with low-and intermediate-risk of surgery. 1 Post-TAVR stroke causes acute and long-term morbidity and mortality. The stroke rate 30 days after TAVR was reported as 3.4% in low-risk patients. 2 Prior studies including intermediate-and high-surgical risk cases suggested the use of the SENTINEL Cerebral Protection System (SENTINEL-CPS) during TAVR may reduce the incidence of ischemic stroke and in-hospital mortality. 3,4 However, the effectiveness of the SENTINEL-CPS during TAVR in lower-risk patients has not been studied yet. The SENTINEL-LIR study (Cerebral Protection of Acute Embolic Burden During Transcatheter Aortic Valve Implantation in Low to Intermediate Risk Patients) aimed to quantify the frequency of embolic debris captured by the SENTINEL-CPS in lower-risk TAVR cases.
We will make the data available upon reasonable request. The SENTINEL-LIR registry was a multicenter, prospective clinical study (URL: https://www.clinicaltrials.gov; Unique identifier: NCT04131127). All patients provided written informed consent. The study protocol was approved by the institutional ethics review committee at each site. Patients with severe, symptomatic aortic stenosis, undergoing transfemoral TAVR with planned use of the SENTINEL-CPS, and a Society of Thoracic Surgeons Predicted Risk of Mortality score of <4% were included. Exclusion criteria were (1) a history of stroke or transient ischemic attack within 6 months of TAVR, (2) carotid artery intervention within 6 weeks of TAVR, (3) prior aortic valve replacement, or (4) concomitant surgical procedure. The clinical team decided the types of transcatheter heart valves implanted (CoreValve Evolut Pro, Medtronic; or Sapien 3, Edwards).The incidence of debris, size, and tissue types captured by the SENTINEL-CPS were histologically analyzed. The details of sample processing and analysis methods have been described previously. 4 Fifty-five percent of patients received the Cor-eValve, while 45% had theSapien 3. Predilatation and postdilatation were performed in 43% and 18% of cases, respectively. The frequency of predilatation and postdilatation were not different between the 2 transcatheter heart valves (predilatation: CoreValve 37% versus Sapien 50%, P=0.36; postdilatation: 15% versus 23%, P=0.48). Both proximal and distal filters of the SENTI-NEL-CPS were successfully placed in all patients. The SENTINEL-CPS was delivered and retrieved via radial access in 96%, brachial access in 2%, and ulnar artery approach in 2%. No vascular complications caused by upper extremity access were observed. The rates of death or stroke (as defined by the Valve Academic Research Consortium 2) within 30 days post-TAVR were 2% (1/49, due to myocardial infarction) and 4% (2/49), respectively. This study did not include routine brain imaging evaluation.
Most captured debris had a size of <500 μm (78% were 150-500 μm). Nearly 5% of the captured particles were ≥1000 μm (Figure [B]), and these were detected in 67% of cases. Transcatheter heart valve type did not impact the debris tissue types, particle numbers, or sizes. Calcified particles were more common in patients treated with predilatation (71% versus 43%, P=0.046). However, predilatation or postdilatation did not alter particle numbers or sizes (Figure [C]).
Overall, the results of the present study are align with those of previous studies conducted in the high-surgical risk population, undergoing TAVR with the SENTINEL-CPS, regarding the capture rate of debris, observed tissue types, and size/distributions of debris. 4,5 The current study is the first to explore the SEN-TINEL-CPS in low-or intermediate-risk patients. This study has several limitations. First, due to the small sample size registry, any associations between the incidence of post-TAVR stroke in this lower-risk cohort and the characteristics of debris captured by the SENTI-NEL-CPS could not be evaluated (all cases received the SENTINEL-CPS treatment). Second, the type of transcatheter heart valve was selected at the operators' discretion, not assigned randomly. Thus, the superiority of transcatheter heart valves might not be evaluated precisely. These limitations will be best addressed in the future large-scale randomized studies.
In conclusion, the SENTINEL-LIR study demonstrates that embolic debris capture by the SENTINEL-CPS during TAVR in low-to intermediate-risk patients was similar to that in previous studies conducted among higher-risk patients. Larger size particles (≥1000 μm), which can cause significant vessel obstruction, were present in 67% of cases. These findings suggest lowerrisk patients undergoing TAVR have potentially a similar embolic risk as high-risk patients as evidenced by embolic debris capture.    P=0.17). The majority of debris particles ranged in size from 150 to 499 μm (78% of particles were ≥150 μm in size); 17% of particles were 500-999 μm in size. Particles 1000-1999 μm and ≥2000 μm in size comprised 5% of the captured particles (100-1999 μm: 4%; ≥2000 μm: 1%). These observations were similar among patients implanted with CoreValve and Sapien 3 valves. Boxes with bars in the left graph indicate interquartile ranges corresponding to each median. Whiskers indicate the minima and maxima. Boxes with error bars in the right graph indicate medians and 75% quartiles. C, Effects of predilatation and postdilatation on captured debris. Performing predilatation or postdilatation did not impact the number of particles or the total tissue area of debris observed in the current study ( interquartile ranges corresponding to each median. Whiskers indicate the minima and the maxima. Categorical variables were analyzed with the χ 2 test or Fisher exact method. Non-normally distributed data were compared with the Wilcoxon rank-sum test. A P value <0.05 was considered significant. All statistical analysis was performed utilizing JMP software (version 15.0, SAS, Cary, NC).