1. Review of the Latest OUS Data from the Self-Expanding Valve Studies
Date: Sunday February 24, 2013
Time: 2:30 – 2:40 PM
Location: Washington, DC
Nicolo Piazza, MD, PhD, FRCPC, FESC
McGill University Health Center, Montreal, Canada
German Heart Center Munich, Munich Germany

2. Consulting: Medtronic CoreValve
Nicolo Piazza, MD, PhD
Consulting: Medtronic CoreValve

3. CE Mark Evolution
CoreValve ReValving System (May)
JenaValve (September)
Medtronic CoreValve Evolut (September)
Direct Flow Medical (January)
2007
2008
2009
2010
2011
2012
2013
Edwards SAPIEN (September)
Edwards SAPIEN XT (March)
Symetis (September)
St. Jude Portico (November)

4. Medtronic CoreValve Evolut Manufacturer
JenaValve Technology
Symetis
Acurate TA
Medtronic CoreValve Evolut
Manufacturer
Access
TF, SC, DAo TA TA
TF, SC, DAo
Deployment
Self-expandable
Self-expandable
Self-expandable
Self-expandable
Support structure
Nitinol
Nitinol
Nitinol
Nitinol
Porcine pericardium
Porcine aortic root
Porcine non-coronary leaflet
Porcine pericardium
Leaflets
Figure 34 – A summary of various transcatheter aortic valves and their characteristics.
Porcine pericardium
Skirt
Polyethylene terephalate
Porcine pericardium
Polyurethane
No. valve sizes 4 3 3 1
Annulus range
18-29 mm
21-27 mm
21-27 mm
18-20 mm
Delivery catheter
18F
32F
28F
18F R3
Partially
Partially
Yes
Partially

5. St. Jude Medical Portico Medtronic Engager Edwards Centera
Symetis Accurate TF
Manufacturer
Access TF TA
TF, SC TF
Deployment
Self-expandable
Self-expandable
Self-expandable
Self-expandable
Support structure
Nitinol
Nitinol
Nitinol
Nitinol
Bovine pericardium
Bovine pericardium
Bovine pericardium
Porcine pericardium
Leaflets
Porcine pericardium
Polyethylene terephalate (PET)
Porcine pericardium
Skirt
Polyester
No. valve sizes 2 2 2 3
Annulus range
19-23 mm
19-26 mm
XXX
21-27 mm
Delivery catheter
18F
26F
14F eSheath
18F R3
Yes No
Yes
Yes

6. Clinical overview of CE mark approved devices
Medtronic CoreValve
JenaValve
Symetis Acurate TA
St. Jude Portico

7. Medtronic Clinical Trials
Confirm Efficacy and Optimize Practice
Expand Access to New Populations and Markets
We recognize that clinical studies are critical to improving outcomes, and driving adoption of our therapies. That’s why we are actively investing in our portfolio of rigorously designed clinical trials. We are developing evidence in 3 areas—
Pivotal trials that demonstrate the safety and efficacy of our transcatheter valve devices for regulatory access and reimbursement.
Well designed trials to help expand transcatheter access to new patient populations and new geographic markets.
Confirmatory trials that validate findings in real world settings and help to optimize practice and patient outcomes.
Demonstrate Safety and Efficacy 7

8. Medtronic n =1015 (ADVANCE registry) Aortic regurgitation grade
0 – 27%
1 – 58%
2 – 15%
3 – 0%
4 – 0%
Age, yrs. (SD) – 81±6
Logistic ES, % (SD) – 19±12
Pre-mean gradient – 46 mmHg
30-day mortality – 4.5%
Post-mean gradient – 10 mmHg
Stroke – 3%
Pre-EOA (cm2) – 0.7
Pacemaker – 26%
Post-EOA (cm2) – 1.7

9. JenaValve
First-in-Human: July 2009 to April 2010, single-center (n=12 patients)
CE mark trial: November 2010 to July 2011, 7 center (n=73 patients)
CE mark approval: September 2011
Post-market evaluation: JUPITER registry (ongoing)

10. JenaValve n = 66 (CE mark) Aortic regurgitation grade 0 – 47% 1 – 39%
2 – 14%
3 – 0%
4 – 0%
Age, yrs. (SD) - 83±4
Logistic ES, % (SD) - 28±6
Procedural success – 90%
Pre-mean gradient - 41±16
30-day mortality – 7.6%
Post-mean gradient - 10±7 mmHg
Stroke – 3.0%
Pre-AVA – 0.7±0.2
Pacemaker – 12%
Post-AVA – 1.7±0.6

11. Symetis TA Acurate
First-in-Human trial – Germany, n=40 (2 year follow-up)
CE mark trial – Germany, n=50 (1 year follow-up)
CE mark approval – September 2011
Post-market evaluation – SAVI registry (ongoing) with n>400 patients
Fully percutaneous transapical system to become available in September 4th quarter 2013

12. Symetis TA Acurate n = 90 (First-in-Human, CE mark)
Aortic regurgitation grade
0 – 50%
1 – 49%
2 – 1%
3 – 0%
4 – 0%
Age, yrs. (SD) - 84±4
Logistic ES, % (SD) – 20±9
STS score, % (SD) – 8±6
Procedural success – 94%
30-day mortality – 7.8%
Pre-mean gradient – 50 mmHg
Stroke – 3.0%
Post-mean gradient – 14 mmHg
Pacemaker – 11%

13. Symetis TA Acurate n = 250 (post CE mark) **
Aortic regurgitation grade
0 – xx
1 – xx
2 – xx
3 – xx
4 – xx
Age, yrs. (SD) - xx
Logistic ES, % (SD) – xx
Procedural success – xx
Pre-mean gradient – xx
30-day mortality – 5.6%
Post-mean gradient – xx
Stroke – 1.6%
Pacemaker – 6.8%
**Personal communication

14. Symetis TF
First-in-Human trial – n=20 patients (completed, no mortality) **
CE mark trial – n = 32 patients (currently ongoing, CE mark expected September 2013) **
**Personal communication

15. St. Jude Portico
Canadian First-in-Human trial – June 2011 to June 2012, 2 centers, n=12 patients
European First-in-Human trial – June 2012 to September 2012, 1 center, n=10 patients
CE mark approval – November 2012 for 23 mm St. Jude Portico (30-50 patients for each 23 mm and 25 mm valve size)
Evaluation of 25 mm valve size recently started

16. St. Jude Portico n = 21 (First-in-Human, 23-mm)
Aortic regurgitation grade
0 – 19%
1 – 67% (trivial included)
2 – 14%
3 – 0%
4 – 0%
Age, yrs. (SD) - 84±4
Logistic ES, % (SD) – 19±10
STS score, % (SD) – 7.5±3
Pre-mean gradient – 44 mmHg
30-day mortality – 0%
Post-mean gradient – 11 mmHg
Stroke – 0%
Pre-AVA (cm2) – 0.7
Pacemaker – 0%
Post-AVA (cm2) – 1.5

17. Conclusion
30 day results roughly similar across the spectrum of self-expanding TAV systems
7332
Reported with data 85 90 21

18. CE Mark Evolution
CoreValve ReValving System (May)
JenaValve (September)
Medtronic CoreValve Evolut (September)
Direct Flow Medical (January)
2007
2008
2009
2010
2011
2012
2013
Edwards SAPIEN (September)
Edwards SAPIEN XT (March)
Symetis (September)
St. Jude Portico (November)

19. Winston Churchill (November 1942)
Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.