Neuroprotection During TAVR

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1 Neuroprotection During TAVR Samir Kapadia, MD Professor of Medicine Section head, Interventional Cardiology Director, Cardiac Catheterization Laboratories Cleveland Clinic Cleveland Clinic

2 Disclosure Co PI for Sentinel Trial Cleveland Clinic

3 Outline Risk of Stroke During TAVR Clinical Silent Brain Infarction Timing and mechanism of Stroke Options of Neuroprotection Case Data Ongoing trial Cleveland Clinic

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5 30 Days - All Stroke from PARTNER Trials Cohort B Cohort A NRCA TF TA Leon et al, NEJM Smith et al, NEJM Kodali et al, ACC 2013 Leon et al, ACC 2013 Dewey et al, STS 2012 Cleveland Clinic

6 Timing of Stroke Cleveland Clinic

7 Cleveland Clinic Continued Risk of Stroke TF TAVR (PARTNER)

8 CoreValve Trial : All Stroke Cleveland Clinic Adams, NEJM, 2014

9 Mortality After Stroke and TIA TF TAVR PARTNER Trial Stroke TIA Cleveland Clinic

10 Mortality after Stroke : TAVR Patients CoreValve High Risk Trial No. at Risk Major Stroke No Major Stroke Cleveland Clinic 10

11 Stroke redefined: AHA/ASA consensus Silent brain infarcts seen with DW-MRI increase the risk of clinical infarction by 2 to 4 times in population-based studies. Silent infarcts are well recognized to be associated with several adverse neurological and cognitive consequences: Impaired mobility Physical decline Depression Cognitive dysfunction Dementia Parkinson s disease Alzheimer disease 11 An Updated Definition of Stroke for the 21st Century : A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association, Stroke. published online May 7, 2013 Cleveland Clinic

12 DW-MRI imaging shows silent infarcts in TAVR New lesions found in vast majority of diffusion-weighted MR images (DW-MRI) of the brain following TAVI Cleveland Clinic aneault et al, JACC 2011;58:

13 Emboli Protection Devices TriGuard Cerebral Protection Device Edwards Embrella Embolic Deflector Claret Sentinel Cerebral Protection System Deflector Deflector Filter capture 9F (femoral) 6F (radial) 6F (radial) 240 micron pore size 100 micron pore size 140 micron pore size Aortic arch position Aortic arch position Brachiocephalic and LCC CE Marked CE Marked CE Marked and Commercialized

14 SENTINEL Study Design Pivotal trial confirming the therapeutic importance of embolic debris capture and removal duringtavr 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 US Co-PIs: Samir Kapadia, MD, Cleveland Clinic Susheel Kodali, MD, Columbia U Med German Co-PI: Axel Linke, MD, Leipzig U Population:Subjects with severe symptomatic calcified native aortic valve stenosis who meet the commercially-approved indications for TAVR with the Edwards SapienTHV/XT/S3 or Medtronic CoreValve/Evolut-R N=296 subjects randomized 1:1:1 at sites in the U.S and Germany. SAFETYARM TAVR with Sentinel TEST ARM TAVR with Sentinel CONTROLARM TAVR only Histopathology Safety Follow-up Safety Follow-up MRIAssessments Neurological and NeurocognitiveTests Primary (superiority) Efficacy Endpoint: Reduction in median total new lesion volume assessed by 3T DW-MR by baseline subtraction. Primary (non-inferiority) Safety Endpoint: Occurrence of all MACCE at 30 days. CAUTION: Investigational device. Limited to investigational use by United States law.

15 SENTINEL Endpoints Efficacy Reduction in median total new lesion volume in protected territories between the Imaging Arms (Test and Control Group) as assessed by DW-MRI at Day 4-7 post-procedure. Safety Occurrence of all Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 days compared to a historical performance goal.

16 Sentinel (Claret Medical)

17 Male, 85 year old Ht: cm Wt: kg ALL: NKDA PMHx: CAD/MI, CABG 2006 (L-LAD, V-Dg, PL, PDA) Colon cancer s/p hemicolelctomy Meds: Kcl, captopril, heparin SC, Aspirin, Atorva Echo 1/22 EF 20-25% AS: 89/52, 0.38, 0.12, SVI 22.8 CT - 1/26 CSA 480mm2 Perimeter: 79mm Diam:30x21mm CSA 482cm2 Perimeter: 81.5mm Diam: 31x22mm Access: TF XT Size: #26 Angles : L/Cra 20/23, R/Cau 20/20 Coronary distance : LM 14, RCA 15 Labs (02/02/15) BUN/Cr: 31/1.25 Hgb/Hct: 13/38 Plt: 103 INR: -- Angiogram (12/15/14) LM: 90-95% LAD: 90% LCx: 80% RCA: rpda Patent L-LAD, V-DG, V-PL, V-rPDA

18 6F Right Radial Arterial Access

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29 CLEAN-TAVI Study Design Overview

30 Significant reduction in lesion volume

31 CLEAN-TAVI: Effective protection Control group (no filters) Test group (filters) Representative slices from each of the orthogonal planes showing new lesions at 2d from each arm of CLEAN-TAVI randomized trial of cerebral embolic protection in TAVI testing Claret dual-filter Cerebral Protection System CLEAN-TAVI (manuscript in review) CAUTION: Investigational device. Limited to investigational use by United States law.

32 Conclusion Stroke after TAVR is an important problem. Stroke rate after TAVR may not be worse than stroke after SAVR but it is associated with mortality and morbidity. Risk of stroke is predominantly procedural. If TAVR stroke risk can be reduced further, it can be a differentiated feature from SAVR. Progress is rapid in the field of procedural neuroprotection.