martin b. leon, md - caci years after the...martin b. leon, md columbia university medical center...
TRANSCRIPT
Martin B. Leon, MD
Columbia University Medical CenterCardiovascular Research Foundation
New York City
Sunday, October 29, 2017
12 mins
CACI in Partnership with TCT: 40 Years of Interventional Cardiology
Disclosure Statement of Financial InterestTCT 2017 Denver, CO; Oct 29 – Nov 2, 2017
Martin B. Leon, MD
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
• Grant / Research Support Abbott, Boston Scientific, Edwards
Lifescience, Medtronic
• Consulting Fees / Honoraria Abbott, Boston Scientific
• Shareholder / Equity Cathworks, Claret, Elixir, GDS, Medinol,
Mitralign, Valve Medical
Affiliation / Financial Relationship Company
History
TAVR in Perspective
TAVR in Perspective
History• The “proof-of-concept” first TAVI case
performed by Alain Cribier and his team in Rouen, FR deserves special attention on this 15th year anniversary!
MR
Antegrade Approach:
Guidewire Position
in LV
Valve Positioning
April 16, 2002; FIM-TAVI, Transseptal
April 16, 2002; FIM-TAVI, Transseptal
15 min Post-TAVI
April 16, 2002; FIM-TAVI, Transseptal
Current Role
TAVR in Perspective
TAVR in Perspective
Current Role
• Explosive growth in TAVR worldwide
SOURCE: Credit Suisse TAVI Comment –January 8, 2015. 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
This year > 100,000 and by 2025 almost 300,000!
Estimated Global TAVR Growth
TAVR in Perspective
Current Role
• Explosive growth in TAVR worldwide
“Drivers” of TAVR Growth
1. commitment to evidence-based medicine
2. rapid technology advancement
3. simplification of the procedure
4. striking reduction in complications
2010
2011
2012
2013
2014
2015
2016
Published
Upcoming
Low Intermediate High Extreme
NOTION
PARTNER 3
US Evolut R LR
PARTNER 2A
SURTAVI
PARTNER 1A
Corevalve US HR
PARTNER 1B
Corevalve US ER
REPRISE 3
Symptomatic AS: SAVR Risk
SALUS (stopped)
PORTICO IDE
Medtronic CoreValve/Evolut R
Edwards Sapien/Sapien XT/S3
Boston Lotus
Direct Flow Medical Direct Flow
Abbott Vascular Portico
PARTNER 2 S3i
UK TAVI
Any available TAVR system
2017
2018
2019
2017
REBOOT
CHOICE
PARTNER 2 S3
Investigational devices
SOLVE-TAV
Pipeline of TAVR Trials across the spectrum of aortic stenosis
SCOPE 1
Symetis Acurate Neo
SCOPE 2
NOTION 22020
2021
AS with no
symptoms
TAVR UNLOAD
EARLY TAVR
PARTNER 2B
24 TAVRRCTs
Capodanno D, Leon MB. EuroIntervention 2016
Since 2007, in the U.S., > 15,000 patients have been
enrolled in FDA studies (including 10 RCTs) with multiple generations
of four different TAVR systems!
TAVR Systems with CE-Approval (2007-15)
Courtesy of S. Windecker
TAVR Newcomers Global Landscape (#25)
• Sapien 3
• Evolut R
• Lotus
• Acurate
• Portico
• Direct Flow
• Engager
• Jena Valve
• Centera
• Venus A Valve
• J – Valve Ausper• VitaFlow (Microport)• Taurus One• Trinity• Colibri• Inovare• Thubrikar• Valve Medical• Triskele• BioValve (Biotronik)• MyVal (Meril Lifescience)• HLT Meridian• NVT (Nautilus)• Xeltis• Zurich TEHV
CurrentLeaders!
Future Contenders?
• Dual, independent filter (proximal and distal) cerebral embolic protection device with visible embolic debris capture and removal
• The 3rd generation CE-marked embolic protection device
• Universal size and shape
• Deflectable compound curve sheath facilitates cannulation of LCC
• Right transradial 6F sheath access using a standard 0.014” guidewire
• Filters are out of the way of TAVI delivery catheter and accessories during the TAVI procedure
Proximal Filter(Innominate Artery)
9–15 mm
Distal Filter(LCC Artery)
6.5–10 mm
TAVR Accessory DevicesCerebral Embolic Protection (CEP)
The Minimalist Strategy No general anesthesia; use “conscious sedation”
(MAC) with attendant anesthesiologist
No TEE, but available TTE support
Percutaneous TF access with percutaneous closure
Minimize IV lines, no Foley catheters, careful sedation and pain meds
No ICUs… monitor in recovery area
Rapid ambulation and early discharge plans (1-2 dys)
TAVR Perspectives
> 70% of TAVR cases worldwide aregood candidates for a “minimalist”procedural strategy!Median LOS after TAVR is 2 days atColumbia-NYP Hospital!
6.3%
5.2%
3.7%4.5%
3.5%
2.2%1.6%
1.1% 1.1%
0%
5%
10%
15%
20%
P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF)
All-Cause Mortality at 30 DaysEdwards SAPIEN Valves (As Treated)
175 344 240 271 282 583 491 1072 947
SAPIEN SXT SAPIEN 3
PARTNER 1 and 2 Trials(Overall and TF Patients)
Strokes (All) at 30 DaysEdwards SAPIEN Valves
6.7%
5.6%
4.1% 4.3%
1.5%
2.6%
0%
5%
10%
15%
20%
P1B (TF) P1A (All) P2B (TF) P2B XT (TF) S3HR (All) S3i (All)
179 344 276 284 583 1076
SAPIEN SAPIEN XT SAPIEN 3
Neurologist evaluations (pre- and post)
PARTNER 1 and 2 Trials(Overall and TF Patients)
Moderate/Severe PVL at 30 DaysEdwards SAPIEN Valves
12.0% 11.5%
16.9%
24.2%
2.9%4.2%
0%
10%
20%
30%
40%
50%
P1B (TF) P1A (Overall) P2B (TF) P2B XT (TF) S3HR (Overall) S3i (Overall)
179 344 276 284 583 1076
SAPIEN SAPIEN XT SAPIEN 3
PARTNER I and II TrialsOverall and TF Patients
TAVR in Perspective
Current Role
• Explosive growth in TAVR worldwide• Evolving recommended use guidelines
and expansion of clinical indications
TAVR GuidelinesThe “New” AHA/ACC Focused Update
Severe AS Symptomatic
Low
Surgical Risk Strata
Intermediate High Prohibitive
TAVR
IA
SAVR or TAVR
IA
SAVR or TAVR
IIa B
SAVR
IB
TAVR GuidelinesThe “New” ESC/EACTS VHD Report
Severe AS Symptomatic
Low
Surgical Risk Strata
Prohibitive
TAVR
IB
SAVR
IB
Intermediate or High
SAVR or TAVR
IB
TAVR Risk AssessmentRisk Stratification Redefined
Low Intermediate HighExtreme/
Inoperable
Traditional
Contemporary
Low Intermediate HighExtreme/inop
erableLower risk Higher risk
Courtesy of N. Piazza
• Bioprosthetic aortic valve failure
• Low-risk patients (? all-comers)
• Low-flow, low-gradient AS
• Bicuspid AV disease
• AS + concomitant disease (CAD, MR, AF)
• Severe asymptomatic AS
• Moderate AS + CHF
• High-risk AR
Expanding TAVR Clinical IndicationsA Transformative Technology
at the Crossroads?
TAVR for Bioprosthetic Valve FailureValve-in-Valve
Webb JG et al. JACC 2017;69:2253-62
• 365 high-risk patients with aortic
bioprosthesis failure treated with TAVR
• 30-day and 1-yr all-cause mortality was 2.7%
and 12.4% respectively
TAVR in Perspective
Current Role
• Explosive growth in TAVR worldwide• Evolving recommended use guidelines
and expansion of clinical indications • The Heart Team is now the central
vehicle for managing patients with complex valve disease
TAVR in Perspective
Current Role
• Explosive growth in TAVR worldwide• Evolving recommended use guidelines
and expansion of clinical indications • The Heart Team is now the central
vehicle for managing patients with complex valve disease
• Acceptance of multi-modality imaging for diagnosis, therapy guidance, and FU
TAVR Accessory DevicesNovel Imaging Systems
Multi-modality Imaging is the RULE!
Angio CTA
TTE TEE + 3D
The Future
TAVR in Perspective
TAVR in Perspective
The Future
• Improved disease awareness and access to TAVR (esp. underserved populations)
AS Based on Surgical Experience
(1) Nkomo 2006, Iivanainen 1996, Aronow 1991, Bach 2007, Freed 2010, Iung 2007, Pellikka
2005, Brown 2008, Thourani 2015,
Age
Pa
tie
nts
2015 Severe Symptomatic AS Patients in the U.S.1
Age
Pa
tie
nts
2015 Severe Symptomatic AS Patients in the U.S.1
(1) Nkomo 2006, Iivanainen 1996, Aronow 1991, Bach 2007, Freed 2010, Iung 2007, Pellikka
2005, Brown 2008, Thourani 2015,
AS Including the TAVR Experience
Age
Pa
tie
nts
2015 Severe Symptomatic AS Patients in the U.S.1
(1) Nkomo 2006, Iivanainen 1996, Aronow 1991, Bach 2007, Freed 2010, Iung 2007, Pellikka
2005, Brown 2008, Thourani 2015,
AS Patients Undiagnosed and Untreated
TAVR in Perspective
The Future
• Improved disease awareness and access to TAVR (esp. underserved populations)
• Further innovation of TAVR platforms (e.g. tissue engineered heat valves)
Zurich Tissue Engineered Heart Valve
Courtesy of Simon P. Hoerstrup, MD, PhD
A “Living” Aortic Valve
XeltisEndogenous Tissue Restoration (ETR)
• Synthetic matrix made of novel biobsorbable supramolecular polymers using electrospinning techniques
• Polymer leaflets mounted on nitinol self-expanding frame
• Regrowth of endogenous tissue coincident with bioabsorption of polymer implant
• Natural self-healing anti-inflammatory leafletsValve after
bioabsorption
XeltisEndogenous Tissue Restoration (ETR)
Animal implant
• Synthetic matrix made of novel biobsorbable supramolecular polymers using electrospinning techniques
• Polymer leaflets mounted on nitinol self-expanding frame
• Regrowth of endogenous tissue coincident with bioabsorption of polymer implant
• Natural self-healing anti-inflammatory leaflets
TAVR in Perspective
The Future
• Improved disease awareness and access to TAVR (esp. underserved populations)
• Further innovation of TAVR platforms (e.g. tissue engineered heat valves)
• Realization of ‘completely’ new clinical indications for TAVR - leveraging the advantages of less-invasive Rx
EARLY TAVR TrialStudy Flow
Stress-Test Abnormal
Treadmill Stress-Test
Asymptomatic Severe AS and 2D-TTE (PV ≥4m/s or AVA ≤1 cm2) Exclusion if patient is symptomatic, EF<50%, concomitant surgical indications, bicuspid valve, or STS >8
Stress-Test Normal
Early-TAVR Randomized Trial
CTA and Angiography
TF- TAVR eligibility
Randomization 1:1Stratified by STS (<3 vs >3)
TF- TAVRClinical
Surveillance
Early TAVR Registry
Primary Endpoint (superiority): 2-year composite
of all-cause mortality, all strokes, and repeat
hospitalizations (CV)
Heart Failure
LVEF < 50%
NYHA ≥ 2
Optimal HF
therapy
(OHFT)
Moderate AS
International
Multicenter
Randomized
TAVR
UNLOAD
Trial
R
TAVR +
OHFT
OHFT
Alone
Follow-up:
1 month
6 months
1 year
Clinical
endpoints
Symptoms
Echo
QoL
Primary EndpointHierarchical occurrence of: All-cause death Disabling stroke Hospitalizations for
HF, aortic valve disease
Change in KCCQ
Reduced AFTERLOAD
Improved LV systolic
and diastolic function
TAVR UNLOAD TrialStudy Design
(600 patients, 1:1 Randomized)
TAVR in Perspective
The Future
• Re-defining AS disease classification, pathophysiology, and “trigger points” for intervention
LMP Ventricular Load
PWA Vascular State
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
0 1 2 3 4
Mo
du
lus
(Dyn
es*
s/cm
^2)
Harmonic
Impedance spectrum
Enhanced Prediction Models• Predict who will better benefit
from TAVR• Decide when is the best timing
of intervention
Refine characterization of CV dynamics
to enable
MIT - CRF Collaboration
Redefine the Pathophysiology
TAVR in Perspective
The Future
• Re-defining AS disease classification, pathophysiology, and “trigger points” for intervention
• There are still important knowledge gaps with TAVR which must be resolved (esp. valve leaflet thickening & thrombosis, durability, and optimal adjunctive pharmacotherapy)
Valve Leaflet Abnormalities
Diastole
Systole
Makkar, et al. NEJM 2015
All TAVR systems will certainly demonstrateevidence of valve degeneration during long-term (> 5 years) assessments, especially if echo criteria
are applied in the definitions of durability!
Surgically explanted Sapien and CorveValve THVs
New EU guidance with standardized definitions and endpoints to assess bioprosthetic aortic valve deterioration and failure
Capodanno D et al. Europ Heart J 2017
TAVR Adjunct PharmacologyCustomized Patient-Based Therapy
TAVR is a breakthrough therapy
for our patients!
92 yo man withcritical AS…#1 TAVR at Columbia-NYP
• severe COPD• creat 2.8• previous CABG
(patent LIMA)• EF 30%• Class IV CHF• STS 15.5%