1. Edwards Sapien Transcatheter Valve System: OUS Data
Jean Fajadet, MD, FESC
President-elect of EAPCI
(European Association of Percutaneous Cardiovascular Interventions)
Clinique Pasteur, Toulouse, France

2. I do not have any potential conflict of interest
Potential conflicts of interest
Speaker’s name: Jean FAJADET
I do not have any potential conflict of interest

3. The SOURCE Family of Registries
Timeline
2009
2010
2011
SOURCE COHORT 1
Nov 07
SOURCE COHORT 2
PREVAIL
SOURCE XT EU
SOURCE XT Global 3 3

4. Excluded: 2 Centres / 85 patients
Background:The SOURCE Registry describes the outcomes in a consecutive group of TAVI patients treated with the Edwards SAPIEN Valve in European centres.
COHORT 1:
34 Centres with 1123 patients
Excluded: 2 Centres / 85 patients
Unable to obtain Ethic Cte approval or administrative issues. – =
32 Centres with 1038 patients +
COHORT 2:
40 Centres with 1306 patients –
2 Centres
Elected not to participate. =
TOTAL:
38 Centres with 2344 patients
The SOURCE Registry has:
100% procedure data
30D Data: COH1 – 99.9% | COH2 – 98%
1Yr Data: COH1 – 98% | COH2 – Avail 2011
All consecutively enrolled
Data Extract – 17MAY2010, 30JUL2010 4

5. Methods: Consecutive Patients
The current data is from centres who could provide data on 100% of their consecutively treated patients during this time.
Centres that could not provide this were excluded.
Transfemoral, Transapical, and [(trans-axillary & trans-aortic)=5] cases are included in this consecutive series.
The SOURCE Registry used the 23mm and 26mm Edwards SAPIEN THV requiring 22/24F Transfemoral sheaths and 26F Transapical sheaths. 5

6. Methods
This is a clinical registry. All events and values are site reported and there are no core labs.
The SOURCE Registry Principal Investigators reviewed and adjudicated all clinical and adverse events reported into the Medidata Rave Database. 6

7. The SOURCE Registry – All Total Enrollment
Site Name
Pts
Karlsruhe/Städisches Klinikum + Herzklinik – G Schymik, H Schroefel
204
Frankfurt/Uniklinik – V Schächinger, M Doss 50
Leipzig/Herzzentrum – T Walther, G Schuler
162
Zurich/KlinikimPark + Hirslanden – W Amann, F Bernet
London/St Thomas’ + King’s – M Thomas, O Wendler
149
Lund/Universitetssjukhuset – G Olivecrona, P Johnsson 42
Milan/Monzino – P Bigliogli, M Fusari
113
Jena/Uniklinik – K Hekmat, M Ferrari 39
Hamburg/Uniklink – H Treede, O Franzen
109
Leiden/ – M Schalij, 37
Munich/DHZ – R Lange
106
A Coruna/ – waiting 36
Paris/Bichat – D Himbert, P Nataf 98
Paris/HEGP – D Blanchard, JN Fabiani 34
Mercogliano/Clinica Montevergine –
P Rubino, G Sorrogpago 91
Leuven/Gasthuisberg – C Dubois, P Herijgers 32
Massy/Jacques Cartier – T Lefèvre, M Romano 84
Lübeck/Uniklinik – ED Kraatz, H Sier 30
Essen/Uniklinik – H Eggebrecht, M Thielmann 82
Torino/ – I Sheiban, M Rinaldi
Münster – H Baumgartner, H Reinecke 80
Padova/ – G Isabella, G Gerosa 28
Madrid/S Carlos – C Macaya, E Rodriguez 79
Innsbruck/Uniklinik – L Mueller, T Bartel 26
Milan/S Raff – I Michev, F Maisano
Cambridge/Papworth – C Densem, P Calvert 22
Aarhus/Skejby – HR Andersen, KE Klaaborg 71
Utrecht/ – P Stella, J Kluin 19
Rouen/CHU – H Eltchaninoff, JP Bessou 66
Barcelona/ – A Igual, 17
Bern/Inselspital – P Wenaweser, T Carrel 60
Tampere/ – P Kosonen, M Kohonen 15
Bruxelles/St Luc – P Astarci, J Kefer 59
Vigo/ – A Inigues 14
Athens/Onassis – K Spargias, G Stavridis 55
London/Brompton – M Mullen, N Moat 13
San Sebastian/Gipuzkoa – J Goiti, M Larman 53
University of Hradec Kralove/ – J Stasek, J Vojacek 10
TOTAL
2344
Centers listed in descending order of total enrollment
N=130 patients – one patient identified in earlier presentations has been removed. Was a screening failure due to endocarditis and was not treated.
Patient cohorts are reflective of intent-to-treat groups and not which approach was actually used. One London patient was crossed over to a transapical implantation but he remains in his intended transfemoral group for analysis.
Data Extract – 17MAY2010, 30JUL2010 7

8. SOURCE COHORT 1 Baseline Demographics and Risk FactorsTF
(n=463) TA
(n=575)
P-Value
Age (yrs)
81.7
80.7
0.022
Female
55.1%
55.8% NS
Pulmonary Disease
24.6%
29.9%
Renal Dysfunction
25.5%
32.5%
0.016
Logistic EuroSCORE
25.8
29.0
0.007
Peripheral Vascular Disease
10.6%
28.0%
<0.001
Carotid Artery Stenosis (>50%)
7.1%
17.2%
Incidence of CAD
47.5%
0.020
Porcelain Aorta
4.5%
11.3%
0.001
Prior CABG
17.5%
27.0%
0.003
Mitral valve disease
15.8%
32.0%
Data Snapshot
5/03/2010 8 8

9. SOURCE: COHORT 1 1 Year Survival (All Approaches)
TF KM 1Yr
Mortality = 18.9%
ALL KM 1 Yr
Mortality = 23.9%
TA KM 1Yr
Mortality = 27.9%
30 Day Survival: TA
89.2% TF
93.7%
ALL
91.2%
ALL TA TF
I Yr Survival
76.1%
72.1%
81.1% 9

10. Cohort 1: 1 YR (Events: Late) Freedom From: Stroke, PM, MI
All Data as KM Curves
Cohort 1: 1 YR (Events: Late)
Freedom From: Stroke, PM, MI 10

11. Early Vascular Access Complications
Relationship to 1 Year Mortality (NB 22/24F Device)
Approach
% Survival in Pts who did not have vascular access complications
% Survival in Pts who did have vascular access complications
P-Value TF
83.9%
72.2%
0.0121 TA
73.2%
47.4%
0.0188 11 11

12. Relationship between EuroSCORE and Survival
1 Year Mortality = 21.6%
1 Year Mortality = 26.5%
30 Day Survival:
<20
93.5%
20-40
88.1%
>40
85.7%
I Year Mortality = 40.8%
Strata Group Comparison
Log-Rank Bonferroni adjusted P-value
< 20 vs
0.6142
20-40 vs. > 40
0.0125
< 20 vs. > 40
0.0012
>40
20-40
<20
I Yr Survival
59.2%
73.5%
78.4% 12

13. Relationship between EuroSCORE and Survival
1 Year Mortality = 16.5%
1 Year Mortality = 19.1%
1 Year Mortality = 27.5%
30 Day Survival:
<20
94.7%
20-40
96.0%
>40
83.3%
Strata Group Comparison
Log-Rank Bonferroni adjusted P-value
< 20 vs
1.0000
20-40 vs. > 40
0.0364
< 20 vs. > 40
0.2077
>40
20-40
<20
I Yr Survival
72.5%
83.5%
80.9% 13

14. Myocardial Infarction
Causes of Death
30 Days to 1 Year
ALL
ALL
179
Cardiac
45 (25.1%)
Heart Failure
28 (62.2%)
Myocardial Infarction
6 (13.3%)
Endocarditis
3 (6.7%)
Other*
8 (17.8%)
Non Cardiac
88 (49.2%)
Pulmonary***
21 (23.9%)
Renal Failure
11 (12.5%)
Cancer
10 (11.4%)
Stroke
9 (10.2%)
Gastrointestinal
5 (5.6%)
Other**
32 (36.4%)
Unknown
46 (25.7%)
Sudden Death
18 (39.1%)
Other
10 (21.7%)
Other * = Arrhythmia, cardiac arrest
Other** = Sepsis, vascular access related, major bleeding, infection, suicide, and multiple organ failure
Pulmonary***= Respiratory Failure, Pulmonary Embolism and Pneumonia 14

15. Multivariate Analysis – 1YR Mortality (TA)
Analysis of Maximum Likelihood Estimates
Parameter
P-Value
Hazard Ratio
95% Hazard Ratio Confidence Limits
Scaled Logistic EuroSCORE (%/10)
<.0001
1.200
1.098
1.311
Renal insufficiency / Failure
0.0047
1.592
1.154
2.197
Carotid artery stenosis (over 50%)
0.0014
0.454
0.280
0.737
Liver disease
0.0005
3.154
1.646
6.043
Other
0.0345
1.489
1.029
2.153
Logistic EuroSCORE is most significant predictor for 1 year mortality in transapical patients 15 15

16. Multivariate Analysis – 1YR Mortality (TF)
Analysis of Maximum Likelihood Estimates
Parameter
P-Value
Hazard Ratio
95% Hazard Ratio Confidence Limits
NYHA Class IV
0.0067
1.948
1.203
3.153
Renal insufficiency / Failure
<.0001
2.382
1.553
3.656
Hyperlipidemia / Hypercholesterolemia
0.0293
0.602
0.382
0.950
Systemic Hypertension
0.0317
0.622
0.403
0.959
Smoking
0.0009
2.268
1.399
3.677
Mitral valvuloplasty
0.0040
8.237
1.956
34.690
Coagulopathy
0.0073
5.178
1.558
17.208
Logisitic EuroSCORE is not a predictor for 1 year mortality in patients treated with the transfemoral approach 16

17. Excluded: 2 Centres / 85 patients
Background:The SOURCE Registry describes the outcomes in a consecutive group of TAVI patients treated with the Edwards SAPIEN Valve in European centres.
COHORT 1:
34 Centres with 1123 patients
Excluded: 2 Centres / 85 patients
Unable to obtain Ethic Cte approval or administrative issues. – =
32 Centres with 1038 patients +
COHORT 2:
40 Centres with 1306 patients –
2 Centres
Elected not to participate. =
TOTAL:
38 Centres with 2344 patients
The SOURCE Registry has:
100% procedure data
30D Data: COH1 – 99.9% | COH2 – 98%
1Yr Data: COH1 – 98% | COH2 – Avail 2011
All consecutively enrolled
Data Extract – 17MAY2010, 30JUL2010 17

18. Patient Number / Percentage
Changes in patient groups and “risk” with time (Numbers of patients per category)
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
P-Value
Mean Log EuroSCORE
27.6 ± 15.5
25.5 ± 21.9
0.0079
Patient Number / Percentage
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
P-Value
Log EuroSCORE >20
695 / 66.9%
734 / 56.2%
<.0001
Log EuroSCORE < 20
340 / 32.8%
568 / 43.5%
Need correct number and percentage for Cohort 2
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
P-Value
SAPIEN in prior aortic bioprosthesis
2 / 0.2%
26 / 1.9%
<.0001
This was not anticipated!!
(4 patients included in database outside Cohort 1 and Cohort 2 have been excluded)
Data Extract – 17MAY2010, 30JUL2010 18

19. Has the reduced EuroSCORE resulted in better 30 day survival?
Cohort 1
Cohort 2
30 day survival
91.2%
89.9%
Need survival table in chart
Data Extract – 17MAY2010, 30JUL2010 19

20. 30 Day Survival: “standard risk” Cohort 1 vs. Cohort 2 with ES>20
Patient Number / Percentage
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
P-Value
Log EuroSCORE >20
695 / 66.9%
734 / 56.2%
<.0001
Survival
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
All (N=2344)
P-Value
Log EuroSCORE >20
90.1%
88.2%
89.1%
0.2504
Data Extract – 17MAY2010, 30JUL2010 20

21. 30 Day Survival: “lower risk” Cohort 1 vs. Cohort 2 with ES<20
Patient Number / Percentage
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
P-Value
Log EuroSCORE <20
340 / 32.8%
568 / 43.5%
<.0001
Survival
Category
Cohort 1 (N=1038)
Cohort 2 (N=1306)
All (N=2344)
P-Value
Log EuroSCORE <20
94.1%
92.7%
93.3%
0.4272
Data Extract – 17MAY2010, 30JUL2010 21

22. Demographics and Risk Factors – Overall Group <20 & >20 Why TAVI for <20?
All Treatments < 20 (N=908)
All Treatments >= 20 (N=1429)
All Treatments p- value
NYHA Class IV
83 ( 9.14%)
244 (17.07%)
<.0001
Female
523 (57.60%)
815 (57.03%)
0.6345
Age >= 80 Years
526 (57.93%)
1016 (71.10%)
Smoking
207 (22.80%)
263 (18.40%)
0.0110
Coronary Artery Disease
396 (43.61%)
838 (58.64%)
Congestive Heart Failure
218 (24.01%)
499 (34.92%)
Myocardial Infarction
99 (10.90%)
262 (18.33%)
Carotid artery stenosis (over 50%)
63 ( 6.94%)
218 (15.26%)
Porcelain Aorta
91 (10.02%)
95 ( 6.65%)
0.0037
Mitral valve disease
260 (28.63%)
448 (31.35%)
0.1803
Cancer
182 (20.04%)
186 (13.02%)
Pulmonary disease
206 (22.69%)
389 (27.22%)
0.0149
Pulmonary disease: FEV1 less than 1.0
32 ( 3.52%)
29 ( 2.03%)
0.0327
Renal insufficiency / Failure
195 (21.48%)
476 (33.31%)
Post thoracic radiation therapy
14 ( 1.54%)
6 ( 0.42%)
0.0396
Peripheral vascular disease (non carotid)
123 (13.55%)
346 (24.21%)
PTCA / stent
203 (22.36%)
420 (29.39%)
0.0002
CABG
108 (11.89%)
392 (27.43%)
Carotid endarterectomy / Carotid stent
20 ( 2.20%)
70 ( 4.90%)
0.0009
Prior surgical aortic bioprosthesis in place? (VIV)
6 ( 0.66%)
20 ( 1.40%)
0.0166
“Frailty” not measured
in the SOURCE database
Data Extract – 17MAY2010, 30JUL2010 22

23. Comparison of <20 “lower risk” patient demographics and risk factors in Cohort 1 and 2: Has the pattern of risk changed?
“True risk” in Cohort 2 may have gone “up”.
Comorbidity / Risk Factor
Cohort 1
(N=340)
Cohort 2
(N=568)
P-Value by Cohort
Female
192 ( 56.47%)
331 ( 58.27%)
0.6273
Coronary Artery Disease
141 ( 41.47%)
255 ( 44.89%)
0.3333
Congestive Heart Failure
60 ( 17.65%)
158 ( 27.82%)
0.0005
Carotid artery stenosis (over 50%)
24 ( 7.06%)
39 ( 6.87%)
0.8937
Porcelain Aorta
38 ( 11.18%)
53 ( 9.33%)
0.4242
Mitral valve disease
68 ( 20.00%)
192 ( 33.80%)
<.0001
Pulmonary disease
82 ( 24.12%)
124 ( 21.83%)
0.4613
Renal insufficiency / Failure
62 ( 18.24%)
133 ( 23.42%)
0.0669
Peripheral vascular disease (non carotid)
49 ( 14.41%)
74 ( 13.03%)
0.5497
CABG
43 ( 12.65%)
65 ( 11.44%)
0.5976
Data Extract – 17MAY2010, 30JUL2010 23

24. 1 Year Kaplan Meier Survival: when is Euroscore reflected in survival benefit? Cohort 1 – ES <20 vs. >20
Cohort 1
ES<20
ES>20
1 year survival
79.7%
74.2%
Need survival table
P=0.0529
Data Extract – 17MAY2010, 30JUL2010 24

25. “Valve in valve”: an indication for TAVI?
In The SOURCE Registry transcatheter valve therapy appears to be an emerging indication for the treatment of a failing surgical aortic bioprosthesis.
Can we categorise these patients?
Is there “gold standard” surgical data for redo surgery?

26. “Valve In Valve” Patient Demographics
Risk Factor
Total Prior Surgical Bioprosthesis (N=28)
Age
Female
12 (46.15%)
EuroSCORE
34.06
Peripheral vascular disease (non carotid)
6 (23.08%)
Coronary Artery Disease
11 (42.31%)
Congestive Heart Failure
8 (30.77%)
Myocardial Infarction
Mitral valve disease
PTCA / stent
CABG
7 (26.92%)
VERY HIGH RISK GROUP OF PATIENTS
Data Extract – 17MAY2010, 30JUL2010 26

27. The SOURCE Registry: “Valve in Valve” What valves have been treated
The SOURCE Registry: “Valve in Valve” What valves have been treated? Where next?
Previous bioprostheses include Carpentier Edwards, Hancock, Mitraflow and Mosaic (21-25mm valves).
This patient population was not anticipated at the outset of the SOURCE registry.
Careful data collection planned for this group in the SOURCE XT registry.
Because the patient populations undergoing surgical redo AVR and transcatheter treatment appear so different it will be difficult to compare outcomes. A randomised trial may well be needed to compare these therapies.

28. Conclusions
Outcomes at 1 year for COHORT 1 of The SOURCE Registry show an improvement compared to historical controls.
Survival for the TF approach is now >80%.
There has been a marked improvement in the TA outcomes with survival now similar to historical TF results.
Lower risk TA (<20% euroscore) patients have the same 1 year outcome as TF. 28

29. Conclusions
If the lower profile SAPIEN XT delivery systems result in lower vascular complications this should result in further improvement in 1 year survival. This will be tested in The SOURCE XT Registry. 29

30. Conclusions
There has been a change in the patient population of TAVI patients between Cohort 1 and Cohort 2 of the SOURCE Registry.
This is reflected by an increased number of patients with a Log EuroSCORE of <20 in Cohort 2.
This change has NOT resulted in a reduced 30 day mortality but some features of Cohort 2 (heart failure and mitral regurgitation) suggest “higher risk”.
Relationship between Log Euroscore and mortality possibly represented at 1year.
Urgent need for the development of TAVI risk score to include other factors ie. frailty 30

31. Conclusions “Valve in valve” appears an emerging indication for TAVI.
The “valve in valve” patients in SOURCE are very high risk.
Comparison of redo surgery and “valve in valve” procedure will be difficult in the absence of randomised data.

33. Surgical redo AVR Patient Demographics Contemporary Surgical literature is lacking
Age 56
Ejection Fraction
57%
Age
63.5
Ejection fraction
58%
Perioperative Risk of Redo Aortic Valve Replacement
Ann Thorac Cardiovasc Surg 2009
Christiansen et al
Operative risk of reoperative aortic valve replacement
J Thorac Cardiovasc Surg 2005
Potter et al
Age 56
Ejection Fraction
53%
Reoperative surgery for degenerated aortic bioprostheses: predictors for emergency
Surgery and reoperative mortality: Vogt et al
Eur J Cardiothoarac Surg 2000
Appears “low risk” patient population

34. Risk factors for operative mortality of repeat heart surgery.
Mean age 54.7yrs
Factors associated with operative mortality
- age
- associated coronary bypass grafting
- valve thrombosis or endocarditis
- replacement of mechanical heart valve
Repeat heart valve surgery: Risk factors for operative mortality.
J Thorac Cardiovasc Surg 2001
Jones et al

35. Risk factors for operative mortality of repeat heart surgery.
Predictive risk factors of re-operative AVR mortality
Risk Factor
Operative Mortality
Gender
Male
Female
4.6%
13.3%
Age at reop
<60
60-70
>70 0%
8.5%
12.6%
Ejection Fraction
> 50%
< 50%
6.5%
15.4%
NYHA class
I/II
III IV
2.0%
4.2%
16.0%
Re-operation for bioprosthetic aortic structural failure – risk assessment.
Jamieson et al. Eur J Cardiothorac Surgery 2003