1. Structural Heart Live Cases
Supported by:
Edwards Lifesciences
Bard Inc
Terumo Medical Corp

2. Disclosures
Samin K. Sharma, MD, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, ABIOMED, CSI, Trireme Inc Annapoorna S. Kini, MD, FACC Nothing to disclose George Dangas, MD, FACC Nothing to disclose regarding today’s presentation Allan Stewart, MD Nothing to disclose for today’s case Anelechi Anyanwu, MD

3. October 11th 2016 Structural Heart Live #14: DR, 81 yr. M
Presentation: Worsening dyspnea on exertion NYHA class III
PMH: Severe AS, HTN, HPL, CAD with multiple prior PCI’s, H/o bacterial meningitis in childhood with resultant cognitive impairment, Ex-smoker, Rheumatoid arthritis, Gout
Medications: Aspirin, Atorvastatin, Furosemide, Amlodipine, Allopurinol, Methotrexate
TTE (6/8/16): Severe valvular AS; PG/MG= 88/58mmHg, Doppler valve area = 0.66 cm2, Ao peak velocity = 4.7m/s, LVEF 63%
EKG: Sinus bradycardia with narrow QRS, T inversion in V5-6
Cath (06/29/16): Non-obstructive CAD with patent stents, mild PAH.

4. October 11th 2016 Structural Heart Live Case #14
Contd….
CT Angiography: The bilateral lower extremity peripheral arterial accesses have minimal diameters 10.5mm
STS risk mortality: %
EuroScore II risk: %
Logistic Euroscore mortality: 11.3%
Course: Patient is determined to be intermediate risk for surgical AVR due to history of age and cognitive impairment.
Plan Today: Patient is planned for Edwards Sapien-3 TAVR (23 mm) via percutaneous femoral access and conscious sedation.
SLIDE TO BE EDITED BY JK

5. Transthoracic Echo
Severe valvular aortic stenosis; peak gradient = 85 mmHg, mean gradient = 58 mmHg, Doppler valve area = 0.66 sq cm, Ao peak CW velocity = 4.7 m/sec, LVEF 63%

6. CTA: Aortic Annulus Annulus Max: 25.2 mm Min: 21.3 mm Mean: 23.0 mm
Perimeter = 73.5 mm
Area = 4.10 cm2
Annular angle = 38°
Annulus diameter: 25.2x 21.3mm
Annulus area: 410mm2
Annulus angle: 38°°

7. CTA: SOV and STJ Sinus of Valsalva Mean Diameter = 31.1 mm
Sino-tubular junction height (above annulus)
= 20.9 mm
Ascending aorta = 33 mm
30.0 mm
32.1mm
31.1 mm
RCA: 18.7 mm LM: 18.9 mm

8. CTA: Access – 3D

9. Access: Iliac and common femoral arteries
Rt CIA: 11.4mm Lt CIA: 10.5mm
Rt CFA: 9.7mm Lt CFA: 9.8mm
Calcific Left CFA

10. Valve Sizing: Sapien 3
Our Patient
410 mm2
23.2 mm

11. SAPIEN Platforms in PARTNER
Device Evolution

12. Summary of Case - 81 year old male - NYHA Class III
- TTE: AS – mean gradient 58 mmHg
STS mortality: 1.5%
EuroScore II mortality: 1.96%
Logistic Euroscore mortality: 11.3%
Course: Patient is determined to be intermediate risk for surgical AVR due to age & cognitive impairment
For 23 mm Edwards Sapien 3 valve via percutaneous femoral approach under conscious sedation.

13. Issues Related To The Case
Increasing Benefit of TAVR in Intermediate Risk Group

15. Total and Annual Number of TAVR Candidates in the Individual Countries
Total of TAVR Candidates in Different Countries Under Current Treatment Indications
Annual Number of TAVR Candidates in Different Countries Under Current Treatment Indications
Approx 3.4% of population beyond 75yrs
have severe AS = 300,000 in USA
Osnabrugge et al., J Am Coll Cardiol 2013;62:1002

17. K-M Curves of H-R Pts Treated with TAVR or SAVR
with a STS Predictor Score of 7% or Less at 2 Yrs
All-Cause Mortality
Cardiovascular Mortality
Reardon et al., JAMA Cardiol August 2016 Epub

18. Clinical Outcomes at 2 Yrs for H-R Patients Treated
with TAVR or SAVR with STS PROM Score of <7%
TAVR (n=202)
SAVR (n=181)
p=0.01
p=0.001
p=<0.001
p=0.01
p=<0.001
p=0.31 %
p=0.01
Reardon et al., JAMA Cardiol August 2016 Epub

20. FRANCE-2 Registry: Late Outcomes of TAVR
in High-Risk Patients for 3-Year Follow-Up (n=4201)
(n=1731)
(n=727)
<20% (n=2341)
20%-30% (n=936)
>30% (n=917)
TF (n=3064)
TA (n=735)
SC (n=242)
0-1 (n=3072)
2-4 (n=529)
Gilard et al. J Am Coll Cardiol 2016;68:1637

21. FRANCE-2 Registry: Multivariate Predictors
Of 3-Year All-Cause Mortality
Gilard et al. J Am Coll Cardiol 2016;68:1637

22. FRANCE-2 Registry: Cardiovascular Events Occurring at Different Time Periods After TAVR
0-1 Month (n=3999)
1-12 Months (n=3522)
1-2 Year (n=2966)
2-3 Year (n=2522) %
Gilard et al. J Am Coll Cardiol 2016;68:1637

23. Echocardiographic Measurements for All Time Points
FRANCE-2 Registry:
Echocardiographic Evaluation of Valve Performance Before and After TAVR and During 3-Yr Follow-Up
Echocardiographic Measurements for All Time Points
Gilard et al. J Am Coll Cardiol 2016;68:1637

25. PARTNER 2A Trial: Study Design
Randomized Patients n = 2032
Symptomatic Severe Aortic Stenosis
ASSESSMENT by Heart Valve Team Operable (STS ≥ 4%)
TF TAVR
(n = 775)
Surgical AVR
VS.
ASSESSMENT: Transfemoral Access
Transapical (TA) / TransAortic (TAo)
Transfemoral (TF)
1:1 Randomization (n = 482)
1:1 Randomization (n = 1550)
TA/TAo TAVR
(n = 236)
Surgical AVR (n = 246)
Yes No
Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years
CR Smith, ACC 2016

26. PARTNER 2A Trial: Primary Endpoint (ITT)
All-Cause Mortality or Disabling Stroke 10 20 30 40 50
TAVR
Surgery
p (log rank) = 0.253
HR [95% CI] = 0.89 [0.73, 1.09]
All-Cause Mortality or Disabling Stroke (%)
21.1%
16.4%
19.3%
8.0%
14.5%
6.1% 3 6 9 12 15 18 21 24
Months from Procedure
Leon M et al. NEJM 2016;374:1609

27. PARTNER 2A Trial: Primary Endpoint (ITT)
All-Cause Mortality or Disabling Stroke
p (log rank) = 0.05
HR: 0.79 [95% CI: 0.62, 1.00]
16.8%
20.4% 3 6 9 12 15 18 21 24 10 20 30 40 50
15.9%
7.7%
12.3%
4.9%
TF TAVR
TF Surgery
All-Cause Mortality or Disabling Stroke (%)
Months from Procedure
Leon M et al. NEJM 2016;374:1609

28. PARTNER 2A Trial: Clinical Endpoints (ITT)
at 2 Years
TAVR (n=1011)
SAVR (n=1021)
p=0.33
p=0.45
p=0.29
p=0.005
p=0.67 %
p=0.83
p=0.02
Death/stroke Death All stroke Disabling Major vasc PPM AKI
stroke compl
Leon M et al. NEJM 2016;374:1609

29. PARTNER 2A Trial: Severity of PVR at 30 Days and
All-Cause Mortality at 2 Years (VI)
14.1%
13.5%
34.0% 10 20 30 40 50 3 6 9 12 15 18 21 24
Overall Log-Rank p = 0.001
None/Trace
Mild
Moderate/Severe
Mod/Sev (reference = None/Trace)
p (Log-Rank) < 0.001
All-Cause Mortality (%)
Months from Procedure
Leon M et al. NEJM 2016;374:1609

30. Sapien-3 Observational Study: The PARTNER 2A and S3i Trial Lancet On-line

31. The PARTNER 2A and S3i Trials: Study Design
Intermediate Risk Symptomatic Severe Aortic Stenosis
Intermediate Risk ASSESSMENT by Heart Valve Team
P2 S3i
n = 1078
ASSESSMENT: Optimal Valve Delivery Access
TA/TAo TAVR
SAPIEN 3
Transapical /
Transaortic (TA/TAo)
TF TAVR
Transfemoral (TF)
P2A
n = 2032
ASSESSMENT: Transfemoral Access
Transapical /
TransAortic (TA/TAo)
Transfemoral (TF)
1:1 Randomization
Yes No
TF TAVR SAPIEN XT
Surgical AVR VS
TA/Tao TAVR
SAPIEN 3
Primary Endpoint: All-Cause Mortality, All Stroke, or Mod/Sev AR at One Year (Non-inferiority Propensity Score Analysis)
Thourani , ACC 2016

32. Sapien-3 Trial: Unadjusted Time-to-
Event Analysis – All-Cause Mortality and All Stroke (AT)
1077
1012
987
962
930
944
805
786
757
743 10 20 30 40 3 6 9 12
2.0%
8.0%
8.4%
16.6%
All-Cause Mortality / Stroke Rate (%)
SAPIEN 3 TAVR
P2A Surgery
Number at risk:
S3 TAVR
Months from Procedure
Thourani et al. Lancet 2016;386:2218

33. Sapien 3 Observation Study:
Outcomes at 1 Year
Sapien 3 TAVR (n=1077)
SAVR (n=944) %
Death Stroke Disabling All-cause Rehosp New PPM
stroke death
Thourani et al. Lancet 2016;386:2218

35. CoreValve US Pivotal SURTAVI Trial: Design
Severe AS Indication for AVR
Separate randomization for AS+CAD
Heart Team Discussion
Europe: STS mortality risk score > 3% and < 8%
US: STS mortality risk score > 4 and < 10%
Yes
Suitable for Randomization No
Non-randomization Registries
1:1 Randomization
N = 1400
N = 1760
AVR Control
N = 220
TAVI VS
AVR
TAVI VS
Medical Management
Primary Endpoint: All cause Mortality and Stroke at 2 yrs
N = 220
Endpoint: All-cause Mortality at 2 yrs
Trial has completed enrollment and data will be presented in AHA 2017 35

36. Insights from the STS/ACC TVT Registry
Relationship Between Procedure Volume and Outcome for Transcatheter Aortic Valve Replacement in U.S. Clinical Practice:
Insights from the STS/ACC TVT Registry

37. There is a Range of TAVR Mortality in US Practice
Risk Adjustment:
Using variables from the previously developed TVT in-hospital mortality model.
Edwards et al., JAMA, Epub March 9, 2016

38. TAVR Complications: Transfemoral Population
In-Hospital Outcomes - Volume
Mortality Vascular complications Bleeding Complications
Unadjusted
Adjusted
Adjusted
Adjusted
Unadjusted
Unadjusted
P Value for Association
Unadjusted = <0.0001
Adjusted =
Unadjusted = <0.0001
Adjusted = <0.0001
JD Carroll, ACC 2016

39. The PARTNER 3 Trial: Study Design
Symptomatic Severe Calcific Aortic Stenosis
Age <65yrs
Low Risk ASSESSMENT by Heart Team
(STS < 3%, TF only)
PARTNER 3 Registries
1:1 Randomization (n=1228)
Alternative Access (n=100) (TA/TAo/Subclavian)
TF - TAVR
(SAPIEN 3)
Surgery
(Bioprosthetic Valve)
CT Imaging Sub-Study (n=200)
CT Imaging Sub-Study (n=200)
Bicuspid Valves
(n=100)
Actigraphy/QoL Sub-Study (n=100)
Actigraphy/QoL Sub-Study (n=100)
ViV (AV and MV)
(n=100)
Primary Endpoint:
Composite of all-cause mortality, all strokes, or
re-hospitalization at 1 year post-procedure
Follow-up: 30 days, 6 mos, 1 year and annually through 10 years

40. Medtronic TAVR in Low Risk Patients
Trial Design & leaflet Sub-study
Patient Population: Low Risk Cohort
Determined by Heart Team to be low surgical risk
Primary Endpoint:
Safety: Death, all stroke, life-threatening bleed, major vascular complications or AKI at 30 days
Efficacy: Death or major stroke at 2 yrs
Sample Size: ~1200 Subjects
Follow-up Evaluations:
30-days, 6-month , 18-month, and
1 through for 5 years
Number of Sites: Up to 80 sites

41. Cumulative TAVR Procedures: TVT Registry 2012 to 2014 TAVR in USA
Procedural Performance and Outcome of TAVR since FDA Approval
65%
35%
2016 Projections: ≈3000 TAVR per month in USA
Holmes et al., J Am Coll Cardiol 2015

42. Estimated Global TAVR Procedure Growth
SOURCE: Credit Suisse TAVI Comment –January 8, ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW
In the next 10 years, TAVR growth will increase X4!

43. Take Home Message: Increasing Benefit of TAVR in Intermediate Risk
RCT and carefully planned registries involving severe AS pts have shown the superiority of TAVR over SAVR including numerically lower neurological events. These observations have resulted in approval of Sapien TAVR in intermediate risk AS pts
Long-term data of TAVR valve durability will be studied and essential in the low risk AS trials. Overall TAVR valve hemodynamics studies have shown valve gradient to be stable for 4-5 years of careful F/U. Ongoing studies utilizing 4D CTA will prospectively answer the question of TAVR vs SAVR valve durability.

44. Question # 1
Following is the true statement about benefit of TAVR vs SAVR in the PARTNER IIA trial:
TAVR had significantly lower mortality than SAVR
TAVR had lower CVA rates than SAVR
TF TAVR had significantly lower mortality than SAVR
TAVR had similar PPM rates than SAVR

45. Question # 2
FRANCE-2 long-term follow-up study has shown the following except:
Majority of neurological events occurs early
Majority of death on long-term occur from non-cardiac cause
There is gradual deterioration of the TAVR valve on echo after 1 year
Majority of PPM are implanted in first 30 days

46. Question # 3
Which of the following is the exclusion for the ongoing low risk trials of TAVR vs SAVR:
A. Bicuspid aortic valve stenosis
B. STS of <3
C. Femoral arteries size >6mm
D. Age <65yrs

47. Correct answer: C Question # 1
Following is the true statement about benefit of TAVR vs SAVR in the PARTNER IIA trial:
TAVR had significantly lower mortality than SAVR
TAVR had lower CVA rates than SAVR
TF TAVR had significantly lower mortality than SAVR
TAVR had similar PPM rates than SAVR
Correct answer: C

48. Correct answer: C Question # 2
FRANCE-2 long-term follow-up study has shown the following except:
Majority of neurological events occurs early
Majority of death on long-term occur from non-cardiac cause
There is gradual deterioration of the TAVR valve on echo after 1 year
Majority of PPM are implanted in first 30 days
Correct answer: C

49. Correct answer: A Question # 3
Which of the following is the exclusion for the ongoing low risk trials of TAVR vs SAVR:
A. Bicuspid aortic valve stenosis
B. STS of <3
C. Femoral arteries size >6mm
D. Age <65yrs
Correct answer: A