1. ONE-YEAR OUTCOMES OLAF WENDLER, MD PHD FRCS
ON BEHALF OF THE SOURCE 3 INVESTIGATORS

2. Potential Conflicts of Interest
Speaker's name: Olaf Wendler
I have the following potential conflicts of interest to report:
Consultant to Edwards Lifesciences

3. Design and Execution Patients 1946 Enrollment July 2014 – Oct 2015
Centres 80
Countries 10
Access Routes
TF, TA, TAo, SC, TC
THV
SAPIEN 3™
23mm, 26mm, 29mm
Clinical Endpoint Adjudication
Independent CEC, VARC 2 Definitions
Follow-up
30 Days, Annually to 5 Years

4. Study Administration Principal Investigators Olaf Wendler, MD
King’s College Hospital, London, UK
Alec Vahanian, MD
Hôpital Bichat, Paris, France
Clinical Events Committee Chairman: Philip Urban, MD
Hôpital de La Tour, Meyrin, Switzerland
Echo Sub-study Core Laboratory José Luis Zamorano, MD
University Hospital Ramon y Cajal, Madrid, Spain
Steering Committee Helmut Baumgartner, MD
University Clinics, Muenster, Germany
Nicolas Dumonteil, MD
Clinique Pasteur, Toulouse, France
Franz-Josef Neumann, MD
University Heart Center, Bad Krozingen, Germany
Gerhard Schymik, MD
Municipal Hospital, Karlsruhe, Germany
Giuseppe Tarantini, MD
Policlinico Universitario, Padova, Italy
Hendrik Treede, MD
University Clinics, Halle, Germany

5. Top 30 Enrolling Centers
SITE
PATIENTS
Municipal Hospital, Karlsruhe, Germany
133
King’s Health Partners, London, UK
107
Kerckhoff Clinic, Bad Nauheim, Germany 99
German Heart Center, Munich, Germany 92
Heart Center, Bad Segeberg, Germany 66
University Clinics (UKE), Hamburg,
Germany 61
Institut Jacques Cartier, Massy, France 60
University Hospital, Angers, France 52
University Hospital, Kiel, Germany
Aarhus University Hospital, Skejby, Denmark 49
Asklepios Clinic, Hamburg, Germany 48
Charles Nicolle Hospital, Rouen, France
University Hospital La Timone, Marseille, France 40
Institut Mutualiste Montsouris, Paris, France
University Hospital, Strasbourg, France 38
SITE
PATIENTS
University Hospital La Cavalle Blanche – Brest, France 37
Centre Cardiologique du Nord Saint-Denis, France 36
University Clinics, Ulm, Germany 35
University Hospital, Clermont-Ferrand, France 34
University Hospital Laennec, Nantes, France
University Hospital, Bern, Switzerland 33
University Clinics, Muenster, Germany
Herzzentrum Brandenburg, Bernau, Germany
Helios Clinics, Siegburg, Germany 32
University Hospital, Lille, France 30
University Medical Center, Utrecht, The Netherlands
Hôpital Bichat, Paris, France 29
DHZ Bad Oeynhausen, Germany
Hospital Clinics, Augsburg, Germany 28
University Hospital Rangueil, Toulouse, France 27

6. Baseline Characteristics
Total
N=1946 TF
N=1694
Non-TF
N=251
p-value
Age (years ±SD)
81.6 ±6.7
81.7 ±6.7
80.8 ±6.4
0.025
Female (%) 48
49.2
39.7
0.006
BMI (mean ±SD)
27.0 ±5.0
27.0 ±5.1
26.82 ±4.6
0.75
Chronic Lung Disease (%)
11.9 11
17.9
0.003
Renal Insufficiency (%)
27.5
26.9
31.7
0.11
Log EuroSCORE (med)
14.42
13.96
17.83
<0.001
<10 (%)
29.0
30.6
18.5
>30 (%)
15.8
14.5
24.6
(Wendler et al. Circulation 2017)

7. Cardiovascular Characteristics
Total
N=1946 TF
N=1694
Non-TF
N=251
p-value
LVEF <30% (%)
6.0
6.3
4.2
0.28
Congestive Heart Failure (%)
36.3
34.8
46.8
<0.001
Prior CABG (%)
11.4
9.4
24.6
Prior PCI (%)
33.8
32.7
41.7
0.005
Porcelain Aorta (%)
4.8
3.5
13.5
Prior Stroke (%)
8.4
7.8
12.7
0.014
Carotid Artery Disease (%)
15.4
13.9
25.4
Peripheral Vascular Disease (%)
15.2
11.9
37.3

8. Procedural Information
Total
N=1946
TF Approach (%)
87.1
Percutaneous/Closure Device (%)
93.0
Conscious Sedation (%)
53.0
No Pre-BAV (%)
50.5
Correct Placement at Intended Site (%)
98.8
Post-Dilation (%)
10.7
Procedure Time (min)
72.8
Fluoroscopy Time (min)
13.9
Contrast Volume (ml)
120.9

9. Survival – Approach (AT Population)
100
88.2% 90
87.4% 80
81.5% 70 60 TF
All
Non-TF 50 3 6 9 12
Months from Procedure
Survival (%)
Number at Risk:
All TF
Non-TF
1946
1903
1866
1853
1824
1804
1779
1754
1736
1722
1691
1649
1436
1694
1661
1628
1617
1594
1579
1561
1541
1528
1517
1489
1455
1262
252
242
238
236
230
225
218
213
208
205
202
194
174

10. Survival – Baseline EuroSCORE (AT Population)
100
89.7% 90
87.4% 80
80.4% 70 60
All
<10
>30 50 3 6 9 12
Months from Procedure
Survival (%)
Number at Risk:
All
1946
1903
1866
1853
1824
1804
1779
1754
1736
1722
1691
1649
1436
Log ES<10
518
509
500
497
490
486
479
472
469
465
459
446
380
Log ES>30
282
266
260
259
253
246
240
236
235
231
227
223
205

11. 1-Year Clinical Outcomes (CEC adjudicated)
Total
N=1946 TF
N=1694
Non-TF
N=251
Mortality (%)
12.6
11.8
18.5
Cardiovascular Mortality (%)
8.0
7.5
11.3
All Stroke (%)
3.1
2.7
5.6
Disabling Stroke (%)
1.4
1.1
3.6
New Onset AF (%)
7.9
7.1
13.3
New Permanent Pacemaker (%)
13.2
13.6
10.4
Endocarditis (%)
1.3
1.2
Clinical Valve Thrombosis (%)
0.4
0.3
0.8
Rehospitalisation* (%)
8.1
8.7
*Rehospitalisations for valve related symptoms or worsening congestive heart failure.

12. NYHA Classification
Total§
TF§
Non-TF§
100
Class IV Class III Class II Class I 90 80 70 60 50 40 30 20 10
% of Population
Baseline 30-Days One-Year Baseline 30-Days One-Year Baseline
§p-value <0.001: Baseline vs. 30-Days and 1-Year
30-Days
One-Year

13. Haemodynamics 50 2
44.1±16
1.6±0.5
1.7±1.4
Mean Ao Gradient (mmHg) 40
1,6 30
1,2
EOA (cm2) 20
0,8
0.7±0.2 10
12.3±5.1
0,4
11.8±5.1
Mean Ao Gradient
EOA
Mean AVG
Baseline
30-Days
One-Year
*AT Population; All Values are CEC adjudicated

14. Paravalvular Regurgitation
Total§
TF§
Non-TF¶
Severe
Paired Analyses p-values between discharge and one-year are § p-value<0.001 and ¶p-value=0.19

15. Causes of Mortality (n=245/1946, 12.6%)
Cardiovascular (n=152, 62%)
30 Days
% (n)
Vascular Injury
18.8 (6)
Heart Failure
9.4 (3)
Cardiogenic Shock
Cardiac Tamponade
6.3 (2)
Fatal Bleeding
31 Days-1 Year
25.0 (30)
Sudden Cardiac Death
11.7 (14)
Endocarditis
10.0 (12)
Stroke
7.5 (9)
Multi-System Organ Failure
3.3 (4)
Non-Cardiovascular (n= 93, 38%)
30 Days
% (n)
Sepsis
33.3 (4)
Pulmonary
Malignancy
16.7 (2)
Multi-system Organ Failure
8.3 (1)
31 Days-1 Year
29.6 (24)
23.5 (19)
12.3 (10)
Cachexia
11.1 (9)
Multi-System Organ Failure
6.2 (5)
*VARC 2 definition

16. Univariate Predictors 1-Year Mortality
Variable
HR*
p-value
Tricuspid Regurgitation Mod-Severe
2.19
<0.001
NYHA IV
2.37
0.109
Renal Insufficiency
2.04
Atrial Fibrillation
1.77
Log EuroSCORE
1.02
Mean Aortic Valve Gradient
0.98
Body Mass Index
0.97
0.021
Procedure Time (Skin-Skin)
1.00
0.150
Transfemoral Access
0.61
0.003
Acute Kidney Injury (≤7d)
3.13
Major Vascular Complications (≤30d)
2.59
ICU Length of Stay
1.07
Days from Implant to Discharge
1.04
Baseline
Peri-Procedural
*HR: Hazard Ratio; All variables with p-value < 0.2 were included in the multivariable analyses

17. Multivariable Predictors 1-Year Mortality
HR [CI]*
p-value
Baseline
Baseline NYHA IV
2.53 [1.25, 5.12]
0.010
Renal Insufficiency
1.30 [1.06, 1.59]
Body Mass Index
0.98 [0.96, 1.00]
0.027
Peri-Procedural
Procedure Time (Skin-Skin)
1.01 [1.00, 1.01]
<0.001
Acute Kidney Injury (≤7d)
1.93 [1.32, 2.83]
ICU Length of Stay (d)
1.05 [1.04, 1.06]
*HR: Hazard Ratio; All variables with p-value < 0.2 were included in the multivariable analyses;

18. SOURCE Registries (n=6953) 1-Year Mortality40
SOURCE ( )
SOURCE XT ( )
SOURCE 3 ( )
All-Cause Mortality (%) 30
23.8% 20
19.4% 10
12.6% 3 6
Time in Months 9 12
Number at Risk:
SOURCE SOURCE XT SOURCE 3
2319
2688
1946
1941
2406
1853
1848
2294
1779
1794
2227
1721
1724
2135
1455

19. SAPIEN 3 Global Experience 1-Year Mortality40
PII S3HR
SOURCE 3 30
All-Cause Mortality (%) 20
14.8% 10
12.6% 3 6
Time in Months 9 12
Number at Risk:
PII S3HR 671
SOURCE
635
1853
601
1779
578
1721
557
1455

20. Conclusions
The low peri-procedural complication rate at 30 days reported in SOURCE 3 has resulted in excellent survival at 1-year.
After 1-year more than 90% of patients are in NYHA I/II.
No severe
PVL has been observed and the rate of
moderate PVL is low (2.6%).
NYHA IV and renal insufficiency are the strongest baseline characteristics to predict 1-year mortality in the multivariable analysis.
These European results from the largest reported registry with SAPIEN 3 are consistent with 1-year outcomes observed in North American trials.

21. Implications The clinical outcomes of SOURCE 3 highlight the
improvements of TAVI treatment in general and the
SAPIEN 3 THV in particular.
The similarities of 30-day and 1-year outcomes of the global experience may indicate that the present balloon- expandable technology has become less dependent of operator variability.
SOURCE 3 provides further evidence on TAVI, however, longer follow-up is vital before TAVI is rolled out to low risk patients.

22. Fast Track Publication
Accepted for
Fast Track Publication