0. Transcatheter Aortic Valve Replacement Update
Eberhard Grube MD
HELIOS Klinikum Siegburg, Germany
Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
Stanford University, Palo Alto, California, USA

1. 70’s - Today
Standard therapy for critical AS is/was Surgical Aortic Valve Replacement
30day Mortality 3%
Options for sAVR:
Mechanical
Tissue
Stentless

2. Outcome of AVR in High Risk Patients with severe AS
Study
# pts
High risk features
In-Hosp mortality
Late mortality
Brogan (1993) 18
LVEF gradient
33% na
Powell (2000) 55
LVEF ≤ 30%
18%
Jegaden (1986) 71
LVEF ≤ 40%
10%
5yr – 28%
Connolly (2000) 52
LVEF ≤ 35% + gradient
21%
3yr – 29%
Pereira (2002) 68 8%
1yr – 18%
Sundt (2000)
133
≥ 80 yo
11%
1yr – 20%
Mortasawi (2000)
105 9%
1yr – 10%
Kohl (2001) 83
13%
1yr – 14%
Bloomstein (2001)
180
≥ 70 yo
17%
Bernard (1992) 23
> 75 yo

3. High Risk AVR Patients with Poor Outcomes
Radiation chest wall/heart disease
Octogenarians with multiple co-morbidities
Cirrhosis with portal hypertension
Porcelain aorta
COPD
Degenerative neurocognitive dysfunction
Previous Cardiac Surgery
ESRD (esp. on dialysis)

4. Surgery
Percutaneous

5. Transcatheter AVR Current Generation Devices Edwards CoreValve
~4,000 patients
CoreValve
~4,000 patients

6. 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 FDA*
(US/OUS, TF/TA 456 pts)
PARVIS
In Planning with FDA
PIVOTAL RCT
* still enrolling patients

7. F.I.M. Balloon Aortic Valvuloplasty First animal implantation (sheep)
THV development
A long road:
20 Years
from concept
to real world
International TF and TA
Feasibility Studies
CE mark
commercialization
2007
20 years
F.I.M. Balloon Aortic Valvuloplasty
1985
Concept of« stented valve », to rule out post-BAV valvular restenosis
1987
1994
Post-mortem studies of intra-valvular stenting
Sketches of stented valve
« Percutaneous Valve Technology » (prototypes)
1999
First animal implantation (sheep)
2000
Large series of animal implantation
F.I.M. PHV implantation
2002
Feasibility Studies (antegrade)
Edwards Lifesciences
Technological improvements
2004
June, 2009 – ~4,000
implanted worldwide

8. TAVI – CoreValve Number of Countries & Centers8

9. TAVI – CoreValve Number of Cases9

10. All SAPIEN® Studies, Transfemoral Continued improvement in implantation success
REVIVE
REVIVAL
PARTNER EU TF
n=61
SOURCE TF
Mean Euroscore (%)
28.8 ± 13.4
34.1 ± 18.0
25.7 ± 11.5
25.7
Procedure time (min)
158 ±-138.5
138.0 ± 63.6
140.9 ± 62
NAV
Fluoroscopy time (min)
30.56 ±7.6
28.1 ± 17
Device success composite incl AR <2+
70.0%
88.9%
91.0
92.5
Freedom from death at 30D
85.9%
92.7%
92%
93.7
Freedom from stroke at 30D
96.7%
90.8%
97%
97.6
Freedom from  MI at 30D
90.9
83.6%
98.4%
99.8
Perforation or damage to vessels, myocardium, valvular structures
15.0%
9.1%
19.7%
17.9
Freedom from reoperation at 30D
99.0%
98.1%
Freedom from Structural valve deterioration 30D
100%
Data Extract
Jan 2009
18 Mar 09
May, 2009 10

11. Edwards Transcatheter AVR Survival at 1, 6 and 12 months
Transfemoral Experience

12. REVIVE & REVIVAL Vascular Complications
Perforations (n=12)
Covered Stent - 3
3 Deaths
Surgical Bypass - 9
Flow Limiting Iliac Dissection (n=4)
In Hospital Mortality in Patients with a Vascular Complication – 36%
In Hospital Mortality in Patients without a Vascular Complication – 10.3%
2 Deaths
Surgical Repair - 4
Vascular Complications (n=25)
Avulsed Iliac Artery (n=3)
Surgical Bypass - 3
Aortic Dissection (n=3)
Surgery - 1
2 Deaths
Medical - 2
Lower Extremity Ischemia (n=4)
Surgery - 2
2 Deaths
Medical - 2 12 12

13. REVIVE improved screening to reduce vascular complications
Vascular Access Complication Rate, by patient
January 2006 – June 2006
30%
Vascular Access Complication Rate, by patient
August 2006 – December 2007
5.8%
Vascular Screening with
Columbia University
Medical Center
Core Lab
INSTITUTED
(in coordination with DSMB)
P = .006 13 13

14. TA Survival PARTNER EU & TRAVERCE
1.0
Overall Survival TRAVERCE vs. PARTNER EU (TA)
6M surv: 0.70
0.8
0.6
Probability (event free)
6M surv: 0.55
0.4
PARTNER EU (TA)
0.2
TRAVERCE
0.0 1 2 3 4 5 6
Time (months)

15. TRAVERCE Transapical Intraprocedural Complications
(18.5%)
Descending Ao dissection 1
Apical bleeding/ventricular injury 8
Arrhythmias requiring intervention 4
Hemodynamic instability requiring intervention 3
Severe CHF
Partial coronary occlusion
Coronary occlusion 2 15

16. TA Survival Overall (n=159)
Leipzig TA Experience Survival
TA Survival Overall (n=159)
1,0
90 ±3%
76 ±4%
74 ±4%
0,8
EuroSCORE 30%
STS Score 15%
Off-pump 94.0%
Conversion %
Stroke None
0,6
0,4
30 Days
6 Months
1 Year
2 Years
0,2
132 78
Pts at risk 64 20
0,0
200
400
600
800
1,000
Days

17. CoreValve Procedural Results 21F S&E 18F S&E 18F EE
NOTE 1: PROCEDURE SUCCESS IS DEFINED AS PATIENT LEAVING PROCEDURE ROOM ALIVE AND WELL WITH FUNCTIONING VALVE
NOTE 2: PROCEDURE TIME IS DEFINED AS FROM “DOOR-IN TO DOOR-OUT”
21F S&E
18F S&E
18F EE 17

18. European Registry (Post-CE Mark)* Australian New Zealand Trial*
Global 18-Fr Experience
18 Fr. CVS
S&E Study – CE Marking
European Registry (Post-CE Mark)*
Australian New Zealand Trial*
Single Center
Experience
Munich
(Lange)
Siegburg
(Grube)
Patients (n)
112 14
1,424 37
137
102
30D Mortality – All Cause
15.2%
7.1%✚
10.4%
8.1%
12.4%
10.8%
Technical Success
86.5%
n.a.
97.3%
98.3%
98.5%
98.2%
* Site reported ✚ Un-adjudicated

19. ≤ 30-Day Adverse Events* 30-Day All Mortality 15.4% 14.5% 6.7%
21F S&E Study
(N = 52)
18F S&E Study
(N = 124)
18F EE Registry
(N = 1243)
30-Day All Mortality
15.4%
14.5%
6.7%
Cardiac Deaths
7.7%
11.2%
3.9%†
Myocardial Infarction
3.8%
3.4%
0.7%
Major Arrhythmias
25.0%
18.5%
4.9%
Pacemaker
17.3%
25.8%
12.2%
Renal Failure
5.8%
4.8%
1.2%
Stroke
6.5%
1.4%
TIA
0.0%
5.6%
0.3%
Structural Valve Dysfunction
Valve Migration
* Multiple events in same patients = data not cumulative
† Includes 4 deaths where cause is not known 19 19

20. Siegburg CoreValve Experience
Total number of patients*: Gen 1 (2005) Gen 2 ( ) Gen 3 (since 2006) in in /week Day Mortality: Gen % Gen % Gen % in %
*Status of Nov 2008

21. Morphological Criteria:
TAVI Candidate Today: Who is Eligible?
Morphological Criteria:
(Mandatory)
Native Aortic Valve Disease
Severe AS: AVAI ≤0.6 cm2/m2
27mm ≥AV annulus ≥20mm
Sino-tubular Junction ≤43mm
Clinical Criteria:
Logistic EuroSCORE ≥20% (21F)
≥15% (18F)
Age ≥80 y (21F)
≥75 y (18F) ?
Age ≥65 y plus 1+ of the following:
Liver cirrhosis (Child A or B)
Pulmonary insufficiency: FEV1<1L
Previous cardiac surgery
PHT (PAP>60mmHg)
Recurrent P.E’s
RV failure
Hostile thorax (radiation, burns,etc)
Severe connective tissue disease
Cachexia

22. Age Distribution of CoreValve Patients 2006-2008
HELIOS Heart Center Siegburg
N=280
Younger Population will be approached with increasing evidence on safety and feasibility…

23. Morphological Quantification
Morphologic Criteria must be met
Morphological Quantification

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

25. Future Challenges Design Features (e.g.Profile) Indication
Controversies:
Which Technique?
Which Access Site?
Which performing Discipline?

26. ‘Percutaneous Devices for Aortic Valve Replacement’
Potential problems of current devices
Paravalvular leackage
Inaccuracies in Positioning
Embolization (Edwards prosthesis)
‘One shot’ procedure

27. CoreValve Aortic Regurgitation post-interventionalB
24.3
28.9
54.4
51.2
19.1
18.2
0.7
1.5
1.7

28. The Sadra LotusTM Valve - Device Features and Rationale
Locking
mechanism
AdaptiveTM Seal

29. Lotus Valve
At this point the device can be fully retracted, back to step 1, and repositioned
And this is the delivery pattern . Retrograde positioning, withdrawal of outer catheter with device expansion, shortening, and release if position is satisfying. This feature of repositioning is certainly very promising and beneficial. So the first clinical results are eagerly awaited to see whether this device might be superior to the current ones or not.

30. Investigational device currently in European clinical trial
The Direct Flow Medical (DFM)
Aortic Valve Prosthesis
Tri-leaflet Valve constructed of Bovine Pericardium
Ventricular and Aortic Rings
-Inflate independently so device can be repositioned
-deflatable so that device can be fully retrieved
Multilumen
Slightly Tapered, Conformable
Polyester Fabric Cuff
Position Fill Lumens (PFLs)
-Used to position/reposition valve
-Complete Inflation Media Exchange
Investigational device currently in European clinical trial
Not available for sale 30

31. Direct Flow Aortic Valve
Valve loaded in Delivery Catheter (22F)
Introducing Tip advanced
Delivery sheath pulled back; Valve inflated

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

33. Transcatheter AVR My Rosey Prophecy
Surgery – The PAST
In the next 5-10 years, most patients with
severe AS requiring AVR will be treated
using transcatheter lesser-invasive
modalities!
TAVR – The Future

34. Vielen Dank