Download Low Risk PARTNER 3

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
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
Consulting Fees/Honoraria
Company
MEDTRONIC
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
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
Global TAVR Market Projection
Global TAVR Market Size
($B)
Range of Analyst Projections
Intermediate Risk (Top 33% Surgical Risk)
STS ≥ 4
$7.0
High Risk (Top 10% Surgical
Risk)
STS ≥ 8
$6.0
Extreme
Risk
$5.0
Inoperable
Low Risk SAVR
$4.0
$3.0
$2.0
$1.0
$-
Piper Jaffrey. 6-21-16. Jefferies 4-26-16. Barclays 4-27-16. UBS 3-21-16.
Goldman Sachs 2-19-16. Morgan Stanley 3-7-16. Cannacord Genuity 4-26-16. JP
Morgan 4-11-16. Morgan Stanley 3-7-16.
80% of patients in STS Database*
Thourani, Annals of Thoracic Surgery, 2015
14%
6%
Cohort C
Do not treat
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
Moderate AS
Asymptomat
Bicuspid
with
ic Severe AS
Heart Failure
Aortic
Insufficiency
Planned
TAV-in-TAV
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
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
1.
2.
Généreux et al. JACC 2016
Nishimura et al. JACC Vol. 63, No. 22, 2014 2014 AHA/ACC Valvular Heart Disease Guideline June 10, 2014:e57–185
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
1)
2)
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, 2014 2014 AHA/ACC Valvular Heart Disease Guideline June 10, 2014:e57–185
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
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
SURTAVI Intermediate Risk Trial will be
presented at ACC 2017
Low Risk
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
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 Study400 Patients
Anatomy
1. Bicuspid
2. Bicuspid
3. Bicuspid
4. Bicuspid
5. Larger valves
For bicuspid valves the
question is anatomy and will
the TAVR valve work in this
anatomy
Risk level is not important to
the anatomy
Physiology
What has already been tested?
Dialysis dependent renal failure
Valve in Valve
Severe MR and/or TR
LF/LG AS
Physiology
What needs to be tested?
AI
Asymptomatic AS
Moderate AS
Complications
Necessary if we want to expand other
indications
PVL
Pace maker
Leaflet motion abnormality
Durability
Conclusions –What Next?
Low Risk
Bicuspid valves
Larger valves
AI
Asymptomatic AS
Moderate AS
Thank You