1. TAVR: How We continue to Refine the Technology and Improve the Results
CRT 2015
Washington DC, February 22nd, 2015
TAVR: How We continue to Refine the Technology and Improve the Results
Eberhard Grube MD, FACC, FSCAI
University Hospital, Dept of Medicine II, Bonn, Germany
Stanford University, Palo Alto, California, USA

2. Eberhard Grube, MD Physician Name Company/Relationship
Eberhard Grube, MD Medtronic, CoreValve: C, SB, AB, OF
Direct Flow: C, SB, AB
Mitralign: AB, SB, E
Boston Scientific: C, SB, AB
Biosensors: E, SB, C, AB
Kona: AB, E
Abbott Vascular: AB
InSeal Medical: AB, E, Valtech: E, SB,
Claret: SB
Keystone: AB
Shockwave: E, AB
Key
G – Grant and or Research Support E – Equity Interests S – Salary, AB – Advisory Board
C – Consulting fees, Honoraria R – Royalty Income I – Intellectual Property Rights
SB – Speaker’s Bureau O – Ownership OF – Other Financial Benefits‘ 2

3. Technology & Core Competencies
Unmet Clinical Needs
Reduce Complications
Deployment Accuracy & Ease of Use
Durability
PVL
Pacemaker Rates
Stroke
Frame
Anatomic Characterization
Delivery Systems
FEA Modeling
Valve Biomaterials
Valve Biomaterials
Predictive Design & Modeling
Procedural Tools
Ex-Vivo Testing
Animal Testing
Capabilities
Technology & Core Competencies

4. Future TAVI
Tools/Enablers to further simplify the procedure & advance outcomes
Frame & Valve
delivery
Tissue engineering
Advanced steering
Advanced sealing
Torqueability
Adaptive sizing
Depth control
Frame advancements
Low Profile Materials

5. Imaging Innovation Potential Solutions Imaging Advancement
Imaging Needs
CT SIZING Support: Assist in valve size decision to minimize PVL potential
Pre-case
FUSION of Echo & Fluoro: Provide more information to implanter during critical placements
Case planning & patient selection
Peri-procedure
Guidance and confirmation
TEE Profile Reduction: Requiring less general anesthesia
Post-procedure
Follow-up and complication prediction
PVL Quantification: Repeatable PVL severity ranking using multiple imaging modalities

6. What is the current status of TAVI? How are today’s outcomes?

7. TAVI Results: PARTNER A and B
Transcatheter aortic valve replacement (TAVR) is a viable treatment strategy for AS patients at high or extreme surgical risk
TAVR has demonstrated significant survival improvements compared to medical management in inoperable patients in the PARTNER B trial1
High risk patients receiving TAVR had similar survival rates to SAVR in the PARTNER A trial2
PARTNER B
PARTNER A
1Kapadia , et al., presented at TCT Kodali S, et al., presented at ACC 2012

8. TAVI Results: US CoreValve Pivotal ER and HR
TAVR demonstrated significant survival improvements compared to medical management in extreme risk patients in the CoreValve US Pivotal Extreme Risk Study
High risk patients receiving TAVR had superior rates to SAVR in the CoreValve US Pivotal High Risk Study
CoreValve Extreme Risk Study
CoreValve High Risk Study

9. Major Procedural Complications are Rare
CoreValve ADVANCE | Procedural Results

10. TAVI – 2015 Access Alternatives
carotid
subclavian/
axillary
direct
aortic
transapical
Iliac-aortic
conduits
transfemoral
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11. TAVI in Failed Surgical Bioprosthetic Valve

12. Remaining TAVI Challenges
Procedure/Technique
Technology
Balloon strategies
Anti-coagulation mgmt
Embolic Protection
Stroke
Sizing
Post-implant intervention (dilation, snare)
Depth of Implant
Frame design
Advanced Sealing
Positioning, Recapture
AR and PVL
Alternative Access
Lower profile
Access specific delivery
Coatings
Vascular Complications
Depth of Implant
Balloon strategies
Frame design
Stable deployment with recapture
Conduction Disturbances

13. Competitive Landscape
CoreValve
Sapien XT
Direct Flow
Lotus
Portico
Symetis
Sapien 3
Centera
Study, Sample Size
US Pivotal Extreme Risk
N=489
PARTNER IIB
N=284
DISCOVER CE N=100 (evaluable cohort N=75)
Reprise II
N=120
Portico CE N=103
Acurate CE N=89 TF
CE Pivotal
N=150
FIM
N=19
30 Day Survival
91.6%
96.5%
98.7%
95.8%
96.4%
96.6%
94.7%
Maj. Vasc Comp
8.2%
9.6%
2.7%
2.5%
5.8%
3.4% 6% 0%
PPM Rate
21.6%
6.4%
16%
28.6%
9.7% 9%
13.3%
15.8%
PVL
41.5% mild, 11.4% mod/severe
75.9% trace/mild,
24.2% mod/severe
28.4% mild, 1.4% mod
20.7% trace/mild, 1.0% moderate
69.3% mild, 4% mod.
4.9% mod
24.1% mild, 3.4% mod
31.6% mild
Stroke
2.3% major
3.2% disabling
2.7% major
1.7% disab.
2.9% major
2.2% major
5.3% stroke/TIA
Coronary Occlusions NR
0.8%
Annulus Rupture
0.1% MI
1.2%
1.8%
1.3%
3.3%
1.9%
Performance acceptable but not optimal yet
Performance acceptable but not optimal, competitive disadvantage

14. What devices are here today and what devices are coming?

15. Clinical Evidence Comparison Reported Implants of CE-Mark Approved Valves (Mainly in Europe)
Medtronic CoreValve
Edwards Sapien / XT
Symetis
ACURATE TA
JenaValve
Portico
Engager
Direct Flow
Lotus
Edwards
Sapien 3
FIM 17 50 12 21 10 31 11 15
CE Pivotal
126
353 40 73
103
125
100
250
150
Medtronic ADVANCE
1,015 NA
FRANCE 2 Registry
1,298
2,635
GARY
3,622
4,758
237
161 92
UK Registry
1,932
2,051 3 35 1
Italian Registry
1,334
Belgian Registry
408
473
Spanish Registry
108
Milan Registry 89
132
Ibero-American
1,220
Swiss Registry
336
317 23
Swedish Registry
311
255
SOURCE Registry
2,307
SOURCE XT Registry
2,706
Other Post-Market Registries
300
180
153
Total Patients
12,116
15,987
594
452
160
227
285
266
165
TOTAL: 30,252 IMPLANTS

16. CoreValve and EDW continue as the TAVR Workhorses … and both have released their Next Generation Devices
Edwards Lifesciences
Sapien 3
Medtronic CoreValve
Evolut R

17. Several new TF and TA valves received CE Mark in 12-18 months

18. Edwards CENTERA Transcatheter Heart Valve
Self-expanding Nitinol frame
Treated bovine pericardium
Contoured frame designed for optimal seating and sealing in the annulus
Low frame height designed to minimize conduction disturbances
Repositionable
23 mm, 26 mm, 29 mm sizes

19. Valve Medical TAVI An Ultra-low Profile System
True 12Fr (catheter O.D.) profile (3.8 mm diameter) for all valve sizes (1st generation)

20. Device Components
Assembled Device
Frame Module
Valve Module
Nitinol self-expanding frame module inserted in optimal annular location
Valve module is reconstituted in ascending Ao
Valve module is docked to frame

21. What technology then is still needed?

22. Vascular Complications
Reduce Complications
PVL
Pacemaker Rates
Stroke
Embolic Protection
Frame advancements
Advanced sealing
Vascular Complications
Optimal Positioning through Repositionability
Adaptive sizing
Frame advancements
Reduce Profile

23. Improve Deployment Accuracy, Ease of Use
New Repositionable Systems
Continued Advancements
Depth control
Torqueability
Advanced steering
Low Profile Materials

24. Continued Trial Follow-up Engineering and Bench Testing
Ensure Durability
Continued Trial Follow-up
Engineering and Bench Testing
FEA Modeling
Tissue engineering
Animal Testing

25. Imaging Innovation Still Needed
Post-procedure
Peri-procedure
Pre-case
Follow-up and complication prediction
Case planning & patient selection
Guidance and confirmation
CT SIZING Support: Assist in valve size decision to minimize PVL potential
FUSION of Echo & Fluoro: Provide more information to implanter during critical placements
TEE Profile Reduction: Requiring less general anesthesia
PVL Quantification: Repeatable PVL severity ranking using multiple imaging modalities

26. Final thoughts…
TAVR in 2015 has been integrated as an important component of the optimal management of complex AS patients.
Although clinical outcomes are favorable, there are still many areas to refine, including procedural complications (esp. strokes, vascular events, and PVL), durability and deployment accuracy
Future device development and clinical research are still needed to resolve these issues 30

27. Thank you very much for Your Attention!