The company’s cerebral protection system has been studied during TAVI as part of post-market evaluation of embolic debris captured in its dual-filter system and hard clinical endpoints such as stroke and mortality.

ULM POST-APPROVAL STUDY
University of Ulm Registry

The aim of this registry was to evaluate the impact of cerebral embolic protection on stroke-free survival in patients undergoing transfemoral aortic valve implantation (TAVI). As background, imaging data on cerebral embolic protection devices have demonstrated a significant reduction in number and volume of cerebral lesions.

A total of 802 consecutive patients were enrolled. The Sentinel Cerebral Embolic Protection (CPS) device was used in 34.9% (n = 280) of consecutive patients. In 65.1% (n = 522) of patients TAVI was performed in the identical setting except without cerebral embolic protection. Neurological follow-up was done within 7 days post-procedure. The primary endpoint was a composite of all-cause mortality or all-stroke according to Valve Academic Research Consortium-2 criteria within 7 days. Propensity score matching was performed to account for possible confounders.

Clinical Results

Both filters of the device were successfully positioned in 280 of 305 (91.8%) consecutive patients. With use of cerebral embolic protection rate of disabling and nondisabling stroke was significantly reduced from 4.6% to 1.4% (p = 0.03; odds ratio: 0.29, 95% confidence interval: 0.10 to 0.93) in the propensity-matched population (n = 560). The primary endpoint occurred significantly less frequently, with 2.1% (n = 6 of 280) in the protected group compared with 6.8% (n = 19 of 280) in the control group (p = 0.01; odds ratio: 0.30; 95% confidence interval: 0.12 to 0.77). In multivariable analysis Society of Thoracic Surgeons score for mortality (p = 0.02) and TAVI without protection (p = 0.02) were independent predictors for the primary endpoint.

In conclusion, in patients undergoing TAVI use of a cerebral embolic protection device demonstrated a significant higher rate of stroke-free survival compared with unprotected TAVI.

Outcome: Propensity-Matched Population

No Cerebral Embolic Protection (n – 280) Cerebral Embolic Protection (n – 280) OR (95% Cl) p Value
Mortality or stroke 19 (6.8) 6 (2.1) 0.30 (0.12-0.77) 0.01
Disabling and Nondisabling stroke 13 (4.6) 4 (1.4) 0.29 (0.10-0.93) 0.03
Disabling 9 (3.2) 1 (0.4) 0.11 (0.01-0.86) 0.01
Nondisabling 4 (1.4) 3 (1.1) 0.75 (0.17-3.38) 0.70
Mortality 8 (2.9) 2 (0.7) 0.25 (0.05-1.20) 0.06
Acute kidney injury stage 2/3 4 (1.4) 3 (1.1) 0.64 (0.15-2.71) 0.54
Major vascular complications 10 (3.6) S (1.8) 0.64 (0.23-1.78) 0.19
Major bleeding 12 (4.3) 4 (1.4) 0.33 (0.11-1.05) 0.05
SENTINEL endpoint* 22 (7.9) 7 (2.1) 0.32 (0.14-0.77) 0.01
Values are n (%) unless otherwise indicated. * All-cause mortality, all stroke, acute kidney injury stage 3.
CI – confidence interval; OR – odds ratio; SENTINEL endpoint – all-cause mortality all stroke, acute kidney injury stage 3.

References

  1.   Seeger J, et al. CEP During Reduces TAVI Significantly Death and Stroke Compared With Unprotected Procedures
MISTRAL POST-APPROVAL STUDY
MISTRAL-I

Recent studies have raised concerns about adverse cerebrovascular events during the TAVI procedure and shortly thereafter. The incidence of early, acute cardiovascular events ranges from 2-6% in different studies. Early cardiovascular events have been associated with embolic debris released during the procedure; however, the etiopathology of the embolized material was uncharacterized.

Claret Medical sponsored a study of 40 patients undergoing TAVI with the use of the company’s dual filter–based embolic protection device in order to determine the composition of embolic material released during TAVI.

Clinical Results

Macroscopic material liberated during the TAVI procedure was captured in the device filter baskets in 75% of cases. The debris was histopathologically analyzed by an independent core lab (CVPath Institute, Gaithersburg, Maryland). The captured material varied in size from 0.15 to 4.0 mm. Overall, thrombotic material was found in 52% of patients, and tissue fragments compatible with aortic valve leaflet or aortic wall origin were found in 52% of patients.

SENTINEL-H POST-APPROVAL STUDY
SENTINEL-H

After receiving CE Mark approval in 2014, Claret Medical initiated the SENTINEL-H post-market observational study to assess real-world performance of the Sentinel Cerebral Protection System (CPS). With Professor C. Naber from Essen, Germany as the Principal Investigator, SENTINEL-H was a prospective, all-comer study that enrolled 217 patients across six centers in Europe. Results of the study were presented in May 2016 at the EuroPCR scientific symposium in Paris, France.

The study was designed to evaluate the effectiveness of the Sentinel CPS in capturing debris during TAVI procedures that utilized a variety of TAVI valves in a real-world clinical setting. The primary endpoint of the study was the rate of capture and the histopathologic analysis of the embolic debris, including total and per-filter embolic debris dimensions, area and debris type characterization; this work was completed and reported by an independent core-lab (CVPath Gaithersburg, USA)

Clinical Results

The results showed that the Sentinel CPS system can be successfully deployed in patients undergoing TAVI in a real-life clinical environment.

Cerebral debris was captured in 99% of the patients (Fig 1). The types of debris captured in the filters included arterial wall, valve tissue, calcification, foreign material and organizing thrombus. Acute thrombus was almost always found in association with other tissue and/or other embolized material, showing that thrombus is not created by the filters. This is debris that would have otherwise entered the cerebral circulation.

There were a mix of older and new generation TAVI valves implanted in this study, described as: self-expandable (SE), balloon-expandable (BE) and mechanically-expandable (ME). (Fig 2) While debris was captured with all valve types, self-expanding valves appear to result in higher rates of embolized valve tissue than balloon-expandable valves (71% vs 43%). Self-expanding TAVI valves may also result in higher rates of arterial wall and calcification debris versus balloon-expandable valves.

Regardless of the TAVI valve type that is implanted, debris was captured and retrieved in virtually every case suggesting that cerebral protection has clinical value even with new generation TAVI valves.

The Sentinel CPS has received the CE Mark and is commercially available in Europe.