1. Claret Cerebral Protection Device: Implications of the Sentinel Study
Axel Linke
University of Leipzig, Heart Center, Leipzig, Germany
Leipzig Heart Institute, Leipzig, Germany

2. Axel Linke, MD
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
Claret Medical Inc. Medtronic, Bard
Medtronic, SJM, Edwards Lifesciences, Symetis, Boston Scientific, Bard
Claret Medical Inc.
None

3. Background – Stroke After TAVR
The true incidence of stroke is most likely UNDER estimated in many studies!!

4. This is just the tip of the iceberg…
68-100% of TAVR patients affected1-10, most patients have multiple infarcts
“Silent” infarcts are associated with:11-13
2-4-fold risk of future stroke
>3-fold risk of mortality
>2-fold risk of dementia
Cognitive decline
1. Rodes-Cabau, et al., JACC 2011; 57(1):18-28
2. Ghanem, et al., JACC 2010; 55(14):
3. Arnold, et al., JACC:CVI 2010; 3(11):1126 –32
7. Bijuklic, et al., JACC: CVI 2015
8. Linke, et al., TCT 2014
9. Vahanian, TCT 2014
4. Kahlert, et al., Circulation. 2010;121:
5. Astarci, et al., EJCTS 2011; 40:475-9
6. Lansky, et al., EHJ 2015; May 19
10. Lansky, et al. London Valves 2015
11. Sacco et al., Stroke 2013
12. Vermeer et al., Stroke 2003
13. Vermeer et al., New Engl J Med 2009

5. The evidence to use of embolic protection in TAVR
reduces ischemic brain volume
CLEAN-TAVI

6. SENTINEL Trial SENTINEL
Pivotal study confirming the therapeutic importance of embolic debris capture and removal during TAVR
Objective: Assess the safety and efficacy of the Claret Medical Sentinel Cerebral Protection System in reducing the volume and number of new ischemic lesions in the brain and their potential impact on neurocognitive function
Primary Investigators:
Samir Kapadia, MD
Cleveland Clinic
Susheel Kodali, MD
Columbia University Medical Ctr
Axel Linke, MD
University of Leipzig, Heart Center
Population: Subjects with severe symptomatic calcified native aortic valve stenosis who meet the commercially-approved indications for TAVR with the Edwards Sapien THV/XT/S3 or Medtronic CoreValve/EvolutR
N=356 subjects randomized 1:1:1
at sites in the U.S and Germany.
SAFETY ARM
TAVR with Sentinel
TEST ARM
TAVR with Sentinel
CONTROL ARM
TAVR only
Histopathology
Safety Follow-up
Safety Follow-up
MRI Assessments
Neurological and Neurocognitive Tests
Primary Efficacy Endpoint: Reduction in median total new lesion volume as assessed by 3Tesla DW-MRI with baseline subtraction.
Primary Safety Endpoint: Occurrence of all MACCE at 30 days.

7. SENTINEL Trial Safety Cohort Imaging Cohort
Patients with Severe Symptomatic Aortic Stenosis Undergoing TAVR
Patients Randomized (1:1:1)
n=363
Safety Cohort
Imaging Cohort
SAFETY ARM
TAVR with Sentinel
(n=123)
TEST ARM
TAVR with Sentinel
(n=121)
CONTROL ARM
TAVR Only
(n=119)
Histopathology & Morphometry
Clinical Follow-Up
Serial MRIs (Baseline, Day 2-7 & Day 30)
Serial Neurocognitive Workup (Baseline, Day 30 & Day 90)

8. Primary Endpoints Safety (Non-inferiority) Efficacy (Superiority)
MACCE at 30 days compared to a historical performance goal
MACCE defined as All Cause Mortality, Stroke, AKI Class 3
As treated analysis utilizing patients from Safety Cohort
Efficacy (Superiority)
Reduction in median total new lesion volume in protected territories as assessed by DW-MRI at Day 2-7 post-procedure
Analysis performed using patients in imaging cohort
Analysis includes all patients that underwent MRI at both Baseline and 2-7 days (paired)
Success endpoint of 30% treatment effect

9. Procedural Characteristics
Control Arm (N=119)
Device Arm (N=121)
Safety Arm (N=123)
P-value1
Sentinel Device Access
0.4918
Radial
N/A
91.2%
95.0%
Brachial
7.0%
4.2%
Both Filters Deployed
92.0%
96.6%
0.1570
At Least One Filter Deployed
99.1%
100.0%
0.4848
Procedure Time2
74.2 ± 40.98
93.2 ± 51.53
81.7 ± 36.59
0.0075
Fluoroscopy Time
16.7 ± 11.50
20.9 ± 13.01
18.0 ± 10.78
0.0493
TAVR Device Used
0.7176
Sapien XT
16.9%
17.5%
19.0%
Sapien 3
53.4%
55.8%
47.9%
CoreValve
5.9%
2.5%
3.3%
CoreValve Evolut R
23.7%
24.2%
29.8%
1 P-values are testing for statistical differences across randomized arms. Continuous data are compared using ANOVA; categorical data are compared using Fisher's exact test.
2Defined as time from first vascular access puncture to achievement of hemostasis at the TAVR access site.

10. Procedural Characteristics
Control Arm (N=119)
Device Arm (N=121)
Safety Arm (N=123)
P-value1
Sentinel Device Access
0.4918
Radial
N/A
91.2%
95.0%
Brachial
7.0%
4.2%
Both Filters Deployed
92.0%
96.6%
0.1570
At Least One Filter Deployed
99.1%
100.0%
0.4848
Procedure Time2
74.2 ± 40.98
93.2 ± 51.53
81.7 ± 36.59
0.0075
Fluoroscopy Time
16.7 ± 11.50
20.9 ± 13.01
18.0 ± 10.78
0.0493
Pre-dilation
42.0%
45.5%
43.1%
0.8709
Post-dilation
13.5%
7.4%
13.8%
0.2121
1 P-values are testing for statistical differences across randomized arms. Continuous data are compared using ANOVA; categorical data are compared using Fisher's exact test.
2Defined as time from first vascular access puncture to achievement of hemostasis at the TAVR access site.

12. Primary Efficacy Endpoint MRI New Lesion Volume (Protected Territories)
42.2% reduction
p=0.33
Study Arm
Count Q1
Median Q3
Whiskers
Device 91
36.9
102.8
423.2
0, 1176
Control 98
34.3
178.0
482.5
0, 949

13. New Lesion Volume –
Protected Territories Adjusted for Baseline lesion volume, Valve Type, Interaction of Valve Type and Treatment Arm

14. Histopathology

15. 30 Day Clinical Outcomes Control Arm Safety + Device Arm p-value
Any MACCE†
9.9% (11/111)
7.3% (17/234)
0.40
Death (all-cause)
1.8% (2/111)
1.3% (3/234)
0.65
Stroke
9.1% (10/110)
5.6% (13/231)
0.25
Disabling
0.9% (1/109)
0.9% (2/231)
1.00
Non-disabling
8.2% (9/110)
4.8% (11/231)
0.22
AKI (Stage 3) 0%
0.4% (1/231)
TIA
Sentinel Access Site Complications
N/A
0.53
†MACCE defined as Death (any cause), Stroke (any), Acute Kidney Injury (Stage 3)

16. Stroke rates as a function of time

17. Summary
Sentinel was successfully deployed in most patients, was ‘safe’ without adverse clinical events, retrieved debris in essentially ‘all’ patients, and numerically reduced both clinical neurologic events and neuroimaging evidence of brain embolization.

18. Personal Implications
Given that stroke rate are still high in TAVR, all TAVR patients are exposed to that risk and that the Sentinel device is safe and effectively captures debris, it should be used in
ALL
TAVR cases.

19. Thank you!