1. Medtronic - Core Valve Eberhard Grube, MD, FACC, FSCAI
CRT 2010
Washington DC, January 21, 2010
Medtronic - Core Valve
Device Evolution, Technique and
Clinical Trial Update
Eberhard Grube, MD, FACC, FSCAI
St.Elisabeth Hospital, Heart Center Rhein-Ruhr, Essen, Germany
Instituto Cardiologico Dante Pazzanese, São Paulo, Brazil

2. Eberhard Grube, MD DISCLOSURES Consulting Fees Honoraria
Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson Company, Medtronic CardioVascular, Inc.
Honoraria
Biosensors International , Boston Scientific Corporation, Medtronic CardioVascular, Inc
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Biosensors International , Medtronic CardioVascular, Inc.
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference off-label use of stents and valve prosthesis.

3. CoreValve Prosthesis

4. CoreValve : 3 Generations
2004
25 fr
21 fr
2005
18 fr
2006
B.Sauren

5. 18 French Procedural Progress
Evolution to a
« true percutaneous cath lab procedure »
within the first 40 Patients of 18 Fr study
Pre-closing with ProStar™
Local Anesthesia
Beating heart in normal sinus rhythm
Valve delivery without rapid pacing
No cardiac assistance
Oct. 2006
Nov. 2006
General anesthesia
Surgical cutdown/repair
Ventricular assistance
Dec. 2006

6. CoreValve 2005
- 24 F 1st Gen CoreValve
- Surgical Prep
- CPB pump
- General anesthesia
CoreValve 2010
- 18 F 3rd Gen CoreValve
- PCI-like procedure

7. Transcatheter AVR Clinical Data Sources
Edwards
CoreValve
Transseptal Experience (RECAST, I-REVIVE; 36 pts)
25 Fr Transfemoral Experience (14 pts)
FIRST-in-MAN
REVIVE (OUS, TF, 106 pts) TRAVERCE (OUS, TA, 172 pts) REVIVAL (US, TF/TA, 95 pts)
21 and 18 Fr Transfemoral OUS Experience (177 pts)
FEASIBILITY
PARTNER EU (OUS, TF/TA 125 pts)
SOURCE (OUS, TF/TA, 598 pts)*
18 Fr Transfemoral OUS Experience (1,243 pts)*
CE-APPROVAL
PARTNER RCT
(US/OUS, TF/TA 456 pts)
CoreValve US Pivotal Trial
In Planning with FDA
PIVOTAL RCT

8. Overall Clinical Experience
Study N
Follow-ups
Status
18 Fr Safety and Efficacy Trial
126
4 years
On-going
Australia-New Zealand Registry
140
2 years
Italian Registry
514 to date
6 months
German Series, Siegburg
>536 to date
30 days
Expanded Evaluation Registry
1483
Up to 2 years
Completed
French Registry
78 to date
6 months
Advance Study
1,000
Up to 10 years
Upcoming
US IDE Study
TBD 10

9. Baseline Clinical Characteristics
18 Fr S&E
(N=126)
Siegburg
(N=86)
ANZ
(N=62)
Age (years)
81.9 ± 6.4
82.3 ± 5.9
83.7 ± 5.4
Female
72 (57.1%)
56 (65%)
30 (48.4%)
NYHA Class I and II
NYHA Class III and IV
32 (25.4%)
94 (74.6%)
15 (17%)
71 (83%)
11 (19.3%)
46 (80.7%)
Logistic EuroSCORE (%)
23.4 ± 13.8
21.7 ± 12.6
18.7 ± 12.9
(N=58)
Peak Pressure Gradient (mmHg)
72.8 ± 23.0
70.9 ± 22.8
Mean Pressure Gradient (mmHg)
47.8 ± 14.3
43.7 ± 15.4
48.6 ± 16.3
Aortic valve area (cm2)
0.73 ± 0.16
0.60 ± 0.16
0.7 ± 0.2 11

10. Procedural success has markedly improved over time
Successful implant defined as no conversion to surgery or device-related mortality during the procedure and proper valve function immediately post-implant. The 18Fr S&E uses technical success (procedural success in re-adjudicated data was 72.6%). 12

11. 30-Day All-Cause Mortality
N = 126
N = 86
30-day all-cause mortality has improved over time 13

12. Pre- and Post-operative Gradients
Peak Gradient (mmHg)
Mean Gradient (mmHg) 14

13. Paired 30-Day NYHA Classification
Change in NYHA Class
Paired 30-Day NYHA Classification 15

14. CoreValve long term Outcomes are quite positive
Number at Risk
Number Failed
Survival (%)
Source: 18 Fr S & E Study: Long-Term Survival
In over 7,500 implants, not a single device migration or fracture was ever reported
The higher leaflets are intended to promote leaflets long term durability and performance
Two-year follow up of 18 Fr S&E shows 63% survival
Longest implant to date from 2004; patient still alive and well.
CoreValve has the only 2-year long term follow up cohort.
And the results are pretty good from a patient’s survival standpoint 16

15. Siegburg CoreValve TAVI Experience
Study
25 F
21 F
18 F
S&E
2008
2009 P
atient n 10 24
102
187
253 T
ime period
2004 -
2005
03/
2006 to
01/
12/
Five years, Three generations, 576 patients

16. In-hospital Events (%) Siegburg CoreValve TAVI Experience

17. CoreValve Clinical Results HELIOS Heart Center Siegburg
% Survival
18F until 08/2009
18F until 03/2008
Days
Survival Curves up to 1 Year

18. CoreValve – The Unsuitable Patient
Severe Calcifications of the Access

19. Complexity / Invasiveness
Which is the preferred access?
Surgical
Transapical
Subclavian
Transfemoral
Interventional
Complexity / Invasiveness

20. Procedural predictors
Predictors for Procedural Success of TAVI
Procedural predictors
Buellesfeld et al. EHJ 2010 in-press

21. CoreValve Delivery Profile and Flexibility are critical
Truly percutaneous delivery: minimizes risk of bleeding and vascular complications
Easier delivery: for less experienced physicians
Treating more patients: delivery is less hindered by peripheral artery disease
Better options for additional approaches: such as subclavian and transaortic approaches
18 Fr
24 Fr
CoreValve is the only system that can offer 18 French across all sizes
Sapien in comparison is trying hard to get to an 18Fr with a new system with their Sapien XT, but inherently they are limited by the fact that they have to fit a balloon into it
Eventually this forces Edwards into awkward maneuvers such as assembling the Sapien XT system within the patient’s body (forcing the balloon inside the Valve).
Besides the potential for ensuing complications during the procedure, this also raise the issue of potential impact to the valve and its durability.
The race towards lower profile shouldn’t come at the expense of performance and patient safety. This is a race where self expanding valves will have the technological upper hand over balloon expandable (because they do not have to fit a balloon inside the valve)
Drawn to scale

22. Low Profile !

23. Lower profile and flexibility means that CoreValve has a low rate of Vascular Complications
Vascular Complications Patrick W. Serruys - PCR'08 Transcatheter aortic valve implantation: State of the art
REVIVAL II
REVIVE
22%
Vancouver TF
12%
18Fr S&E
11% 4%
CoreValve
Edwards

24. Aortic Regurgitation should be avoided
CoreValve Design:
The long sealing tunnel allows the valve to effectively function within a range of depth placements
The conformability of nitinol allows proper apposition of the valve to the native annulus
The supra annular position of the leaflets is a design feature that is meant to allow CoreValve to function better even when the annulus itself is in an out-of-round position
The conformation of the leaflets allow them to have good coaptation and provide durable performance

25. CoreValve is functioning well in Out-of-Round Situations
CoreValve has been shown to retain a round mid-section (where the leaflets are), even when the annulus was out of round
“Dual source MSCT demonstrated incomplete and non-uniform expansion of the CRS frame, but the functionally important mid-segment was well expanded and almost symmetrical. Anatomical under sizing and incomplete apposition of struts was seen in the majority of patients.” (09/09) Schultz CJ, Weustink A, Piazza N, Otten A, Mollet N, Krestin G, van Geuns RJ, de Feyter P, Serruys PW, de Jaegere P. Geometry and degree of apposition of the CoreValve ReValving system with multislice computed tomography after implantation in patients with aortic stenosis. J Am Coll Cardiol 2009;54(10):

26. Aortic Regurgitation(PVL)
Source: 18Fr S&E 33

27. New Permanent Pacemaker within 30 Days
There Is a Higher Incidence of Pacemaker Implant Associated with CoreValve
New Permanent Pacemaker within 30 Days
% patients
Be sure to highlight that Permanent Pacemaker Implant does not mean permanent pacing need
Weighted average = 23%
(n=1990 patients) 34

28. Participating Centers
It is important to remember that Pacemaker Implantation may not mean Pacing Need
New Permanent Pacemaker within 30 Days 18F Safety and Efficacy Study (n=126)
* 2 centers with < 5 implants excluded from the presentation; both centers had 0% 30-day permanent pacemakers
% patients
Highlight that Permanent Pacemaker Implant, which is a clinician’s decision should be differentiated from Pacing indication which is a clinical condition
Participating Centers
Physicians’ decision to prophylactically implant play a big role in the variability among centers 35

29. Rotterdam Experience (n=91)
Depth of Implantation May Play a Role in the Onset of Rhythm Disturbances
Rotterdam Experience (n=91)
New-onset LBBB acquired during or after valve implantation
10.3 mm
No new-onset LBBB or new-onset LBBB acquired during procedure but before valve implantation
7.3 mm
6.0 mm
Pacing is probably due to the impingement of the CoreValve on the conduction system, which passes below the valve.
An excessive depth of implantation is more likely to result in Heart Block
An oversized valve is also probably more likely to result in heart block (increased pressure on surrounding tissue, eventually squeezing the conduction system) 36

30. TAVI PCI sAVR CABG My Prediction: Repetition of an Old Story
2000’s, 2010’s
With the same result…
PCI
CABG
1980’s, 1990’s

31. Thank you for your attention !

32. Questions ?

33. Clinical Experience to Date
Over 7,500 implants to date
Over 243 sites in 29 countries 40 40

34. Thank you for your attention !