1. Expanding Indications for TAVR – What Should Be Next?
Michael J. Reardon, M.D.
Professor of Cardiothoracic Surgery
Allison Family Distinguish Chair of Cardiovascular Research
Houston Methodist DeBakey Heart & Vascular Center

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Consulting Fees/Honoraria
MEDTRONIC

3. Michael J. Reardon, M.D. Serve on the executive steering committees of; Corevalve Extreme and High risk, SURTAVI, Medtronic Low Risk, Reprise III and Reprise IV National PI SURTAVI Medtronic low risk Reprise III Reprise IV

5. TAVR was approved in the US for patients with tri leaflet symptomatic severe aortic stenosis. Extreme and high risk are approved for Corevalve/Evolut R and Sapien. Intermediate is approved for Sapien
Where do we need to go?
Risk
Anatomy
Physiology
Complications

6. Global TAVR Market Projection
Intermediate Risk (Top 33% Surgical Risk)
STS ≥ 4
High Risk (Top 10% Surgical Risk)
STS ≥ 8
Extreme Risk
Inoperable
Cohort C
Do not treat
Low Risk SAVR
80% of patients in STS Database*
14% 6%
Piper Jaffrey Jefferies Barclays UBS Goldman Sachs Morgan Stanley Cannacord Genuity JP Morgan Morgan Stanley
Thourani, Annals of Thoracic Surgery, 2015

7. Asymptomatic Severe AS
Multiple Potential New Indications for TAVR Could Add 100,000 more procedures by 2025
Paradigm shift in procedural risk with TAVR creates opportunities to treat a wider spectrum of patients with aortic valve disease
Bicuspid
Asymptomatic Severe AS
Moderate AS with
Heart Failure
Aortic Insufficiency
Planned
TAV-in-TAV

8. Bicuspid
Bicuspid aortic valves are the most common congenital valvular abnormality, occurring in 1 % - 2% of the general population with male to female ratio of 2:11
Expect to see more bicuspid patients in younger Aortic valve replacement patients2
Technical Challenges Remain for TAVR
Accurate prosthetic sizing to conform to the elliptical bicuspid anatomy
Sufficient sealing to achieve trace/none AR
1 Comparison of the effectiveness of TAVI in patients with STENOTIC bicuspid Versus Tricuspid valves –German TAVI registry – Bauer , Linke et al
2 Frequency by Decades of Unicuspid, Bicuspid, and Tricuspid Aortic Valves in Adults Having Isolated Aortic Valve Replacement for Aortic Stenosis, With or Without Associated Aortic Regurgitation William C. Roberts and Jong M. Ko

9. Asymptomatic Severe Aortic Stenosis with normal EF
Risk of Sudden Cardiac Death ~1%
~3.7 fold increase in all-cause mortality (AVR vs. Medical Therapy)1
Watchful waiting for symptoms may result in irreversible ventricular damage
Challenges:
Patient referral and consent in absence of symptoms
Guidelines are not clear
Généreux et al. JACC 2016
Nishimura et al. JACC Vol. 63, No. 22, AHA/ACC Valvular Heart Disease Guideline June 10, 2014:e57–185

10. Moderate AS with Heart Failure
May prevent the development of irreversible damage to the ventricle
Potential improved rate of LV regression post AVR
Watchful waiting may lead unnecessary delays in treatment
Challenges:
No Established Criteria in Guidelines
Moderate AS patients will require a valve with a large valve area to derive a clinical benefit (>1.5cm²)
No clear definition on which Moderate AS Patients will benefit from AVR
Dweck M. et. Al. “Markers of left ventricular decompensation in aortic stenosis.” Article in Expert Review of Cardiovascular Therapy · May 2014
Nishimura et al. JACC Vol. 63, No. 22, AHA/ACC Valvular Heart Disease Guideline June 10, 2014:e57–185

11. Aortic Insufficiency
Surgical AVR is the gold standard and reports of successful TAVR for extreme risk/inoperable patients
Technical Challenges Remain for TAVR
Stability even in non-calcified valve – Sufficient anchoring
Accurate Prosthetic sizing and larger dimensions to conform valve size needs (in the absence of calcium)
Prevent valve migration
Mortality and Morbidity of Aortic Regurgitation in Clinical Practice Dujardin et al. Circulation 1999

12. TAV – in – TAV
Life time management is key as we start to implant TAVR in younger patients – more patients expected to be a recipient of more than one TAVR in their lifetime.
Technical Challenges Remain for TAVR
Positional Accuracy - Implant depth
No migration upon implant
Good combined hemodynamics outcome
Sufficient perfusion to the coronaries & allow future access to coronaries

13. SURTAVI Intermediate Risk Trial will be presented at ACC 2017
Low Risk

14. PARTNER 3 CoreValve Evolut R
Low Risk, Symptomatic AS
STS <4
Age >65 years
RCT- TAVR vs SAVR
1,228 patients
Nested Registries-3
50 Sites
One year Composite Endpoint
Death
Stroke
Rehospitalization
4D CT Imaging Substudy -400 patients
CoreValve Evolut R
Low Risk Symptomatic AS
STS < 3
No Age Floor
RCT – TAVR vs. SAVR
1,200 patients
80 sites
Two Year Endpoint
Death
Disabling Stroke
Adaptive Design
4D CT Imaging Study- 400 Patients

15. Anatomy
Bicuspid
Larger valves

16. For bicuspid valves the question is anatomy and will the TAVR valve work in this anatomy
Risk level is not important to the anatomy

17. Physiology
What has already been tested?
Dialysis dependent renal failure
Valve in Valve
Severe MR and/or TR
LF/LG AS

18. Physiology
What needs to be tested? AI
Asymptomatic AS
Moderate AS

19. Necessary if we want to expand other indications
Complications
Necessary if we want to expand other indications
PVL
Pace maker
Leaflet motion abnormality
Durability

20. Conclusions –What Next?
Low Risk
Bicuspid valves
Larger valves AI
Asymptomatic AS
Moderate AS

22. Thank You