expanding indications of tavr: ongoing trials and expectations
TRANSCRIPT
Expanding Indications of TAVR:
Ongoing Trials and Expectations
Alan C. Yeung, MD
Li Ka Shing Professor of Medicine
Chief (Clinical), Division of Cardiovascular Medicine
Stanford University School of Medicine
Disclosure Statement of Financial Interest
• Grant/Research Support • Scientific Advisory Board • Executive Physician Council
• Edwards Lifesciences, Abbott • Medtronic, Abbott • Boston Scientific Corp
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
Estimated Global TAVR Growth
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
In the next 10 years, TAVR growth will increase X4!
TAVR Clinical Evidence
Capodanno D and Leon MB. EuroIntervention 2016;12:Y1-Y5.
19 Studies
Primary Endpoint
0 3 6 9 12
496 475 467 462 456 454 408 390 381 377
Number at risk:
TAVR Surgery
Months after Procedure
451 374
TAVR Surgery
Psuperiority= 0.001
HR [95% CI] =
0.54 [0.37, 0.79]
Death
, S
troke, or
Rehosp (
%)
Pnon-inferiority< 0.001
Upper 95% CI of
risk diff = -2.5%
8.5% 9.3%
15.1%
4.2%
0
10
20
The PARTNER 3 Trial
High
Risk
Interm
Risk
Extreme
Risk
Low
Risk
PARTNER 1B
PARTNER 1A PARTNER 2A
PARTNER 3 • RCT 1:1
• vs. Standard Rx
• N = 358 pts
• RCT 1:1
• vs. SAVR
• N = 699
pts
• RCT 1:1
• vs. SAVR
• N = 2032 pts
• RCT 1:1
• vs. Surgery
• N = 1000 pts
79.9%
13.9%
6.2%
Intermediate risk
(STS 4-8%)
Low risk
(STS <4%)
High risk
(STS > 8%)
STS database 2002-2010 (141,905 pts)
Since 2007, in the U.S., >15,000 patients
have been enrolled in FDA studies
(including 6 RCTs) with multiple generations of
two TAVR systems!
• Bioprosthetic aortic valve failure (Low and Inter risk)
• Bicuspid AV disease
• Moderate AS + CHF
• Severe asymptomatic AS
• AS + concomitant disease (CAD, MR, AF)
• High-risk AR
Expanding TAVR Clinical Indications A Transformative Technology
at the Crossroads?
Mortality After VIV TAVR
Dvir, et al. JAMA. 2014; 312(2):162-170
The smaller the surgical valve, the higher the mortality!
VIV TAVR case
21 mm Magna (true ID 19 mm) treated with 23 mm CoreValve Evolut
Baseline Mean gradient: 36 mmHg Aortic valve area: 0.8 cm2
After VIV TAVR Mean gradient: 26 mmHg Aortic valve area: 1.2 cm2
Bioprosthetic Valve Fracture
Final Hemodynamics
Mean gradient: 9 mmHg Aortic valve area: 1.6 cm2
Clinical Results
0
20
40
60
80
40.6 ± 16 p<0.001
8.1 ± 4.8
Baseline After VIV TAVR After BVF
19.0 ± 8.8
p<0.001
Me
an
Re
sid
ua
l G
ra
die
nt
(mm
Hg
)
0
0.5
1
1.5
2
2.5
0.8 ± 0.3
p<0.001
2.1 ± 0.8
Baseline After VIV TAVR After BVF
1.4 ± 0.8
p<0.001
Me
an
Va
lve
EO
A (
cm
2)
66 Patients undergoing VIV TAVR followed by BVF
Presented by Keith B. Allen, Western Thoracic Society Annual Meeting, 2018
The BASILICA Trial: Prospective multi-center investigation of
intentional leaflet laceration to prevent TAVR coronary obstruction
NCT03381989
Jaffar M. Khan BM BCha,b
Adam B Greenbaum MDc,d, Vasilis C Babaliaros MDc,, Toby Rogers BM BCh PhDa,b, Marvin HK Eng MDd, Gaetano Paone MDd, Bradley G Leshnower MDc, Mark Reisman MDe, Lowell Satler MDb, Ron Waksman MDb, Markus Y Chen MDa, Annette M Stine RNa, Xin Tian PhDa, Danny Dvir MDe , Robert J Lederman MDa
a: Division of Intramural Research, National Heart Lung & Blood Inst (NHLBI); b: Medstar Washington Hospital Center; c: Emory University Hospital; d: Henry Ford Hospital; e:
University of Washington jaffar.khan@n
ih.gov
CENTRAL ELIGIBILITY COMMITTEE CRITERIA FOR
CORONARY OBSTRUCTION
Criteria 1 Coronary Ostia Occlusion
• Are aortic leaflets higher than the
coronary ostia? AND
• Is the VTC <4mm?
Criteria 2 Sinus Sequestration
• Do aortic
leaflets reach
the STJ? AND
• Is there risk of sealing the
STJ (by visual assessment
with virtual valve)?
Features that mitigate risk
• Native aortic valves
• Bioprosthetic valves with internally
mounted porcine leaflets
• Functional coronary artery bypass grafts
Features that accentuate risk
• Externally mounted bioprosthetic valve leaflets
• Stentless bioprosthetic valves
• Bioprosthetic valve fracture planned
• Absent coronary filling on BAV angiography
1Ribiero et al JACC 2013
Incidence of BAV in Isolated SAVR
Roberts, WC. Circulation 2005;111:920-925
2 9
30
74
155 149
38
1 0 0 2
25
93
198
98
1 4 6 15
9 11 8 2 0
0
50
100
150
200
250
21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100
Bicuspid (49%)
Tricuspid (45%)
Others (6%)
42%
28%
Age (Year)
932 SAVR patients
BAV Classification
CTA System
27%
5%
68%
(from 14 centers in North America, Europe and Asia)
Tricommissural
3 commissures V-like orifice
“functional or acquired”
Bicommissural Raphe-type
Bicommissural Non Raphe-type
2 commissures, 1 raphe Slit-like orifice
Jilaihawi H. JACC Imaging 2016
2 commissures, no raphe Slit-like orifice
BAV - TAVI Challenges
• Valve sizing: more difficult and requires careful CTA • Valve positioning: implant depth, horizontal Ao • Increased adverse procedural events
valve embolization annulus rupture valve-in-valve conversion to SAVR new pacemakers mod-severe PVL
• Late concerns: durability (incomplete expansion) and aortopathy (untreated)
Recent Multicenter BAV - TAVI Registry
Yoon SH et al. JACC 21;2017:2579-89
TVT BICUSPID REGISTRY AT ACC 2019
TVT Registry Biscuspid vs Tricuspid propensity
matched
N=2691 each (81,822 Sapien 3)
Higher surgical conversion (0.9% vs 0.4%, p=0.03)
Higher annular rupture (0.3% vs 0%, p=0.03)
More second valve needed (0.4% vs 0.2%, p=0.16)
At 30 days, there was no difference in all-cause
mortality, life-threatening bleeding, major vascular
complications, and aortic valve reintervention
Risk of all stroke (2.4% vs 1.6%; P = 0.02) and need
for new pacemaker (9.1% vs 7.5%; P = 0.03). Little
use of CPD.
At 1-year analyses, there were no differences in
mortality, stroke mortality and stroke.
EARLY TAVR Trial Study 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 1:1 Stratified by STS (<3 vs >3)
TF- TAVR Clinical
Surveillance
Early TAVR Registry
Primary Endpoint (superiority): 2-year composite
of all-cause mortality, all strokes, and repeat
hospitalizations (CV)
• Clinical events are very frequent (61% @ 4 yrs FU) • Most events occur in the first year • In patients with events, 25% were NYHA class 1 and 42%
were NYHA class 2
Van Gils et al. JACC 2017;69:2383-92
Primary Endpoint Landmark Analysis
Impact of Moderate AS in Patients with Reduced LV Systolic Function
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 Endpoint Hierarchical 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 Trial Study Design
(600 patients, 1:1 Randomized)
AS and Atrial Fibrillation Watch-TAVR
Aortic Stenosis &
Atrial Fibrillation
TAVR + WATCHMAN
(n = 156)
TAVR +
Medical Rx
(n = 156)
1o Outcome: • Death, stroke, bleeding
@ 1 year 2o Outcome: • Components of primary • Any thromboembolism • Cardiovascular death • Re-hospitalization • QoL (KCCQ-12) • Procedural costs
National PIs: Samir Kapadia & Martin Leon Grant support: Boston Scientific
TAVR in AR Current device not optimal
Registry: 254 patients, 56% Core, 12 days in hospital and 20% pacer.
Current “Standards” for TAVR
MDT Evolut R (PRO) Edwards Sapien 3
“Next in Line” for TAVR
LOTUS (Edge) ACURATE neo PORTICO
JENA Valve CENTERA VENUS A Valve
“Rebooting” or Increasing Momentum