1. First Report of One-Year Outcomes of the REPRISE I Feasibility Study of the Repositionable Lotus Aortic Valve Replacement System
Ian T. Meredith AM
MBBS, PhD, FRACP, FCSANZ, FACC
On behalf of the REPRISE I Investigators
Stephen G. Worthley, MD; Robert J. Whitbourn, MBBS, BMedSc, BSc; Paul Antonis, MBBS; Joseph Montarello, MBBS; Andrew E. Newcomb, MBBS; Dominic J. Allocco, MD; Keith D. Dawkins, MD

2. Disclosures Consultant Fee / Honoraria / Speaker’s Bureau:
Boston Scientific (Modest)
Medtronic (Modest)
The REPRISE I study is sponsored and funded by Boston Scientific Corporation.

3. Lotus Valve System 1. Preloaded delivery system
3. Central radiopaque marker to aid precise positioning
4. Functions early enabling controlled deployment
Fully retrievable and repositionable
Adaptive seal designed to minimize paravalvular leak
Nitinol Frame
Adaptive Seal
2. Simple handle design
Locking Mechanism
Unsheath,
Lock
Release Collar
Sliding Door
Unlock, Resheath
Bovine Pericardium
Center Marker

4. REPRISE I Study Design
OBJECTIVE: Assess acute safety & performance of the Lotus Valve System (23 mm) for TAVR in symptomatic high surgical risk patients with calcified stenotic aortic valves
DESIGN: Prospective, single-arm feasibility study
PRIMARY ENDPOINT: Device success (VARC-1 definition) without in-hospital MACCE through discharge/7 days
SECONDARY ENDPOINTS:
Successful repositioning/retrieval of Lotus Valve System, if attempted
Incidence of prosthetic aortic valve regurgitation by discharge TTE
”Discharge” is defined as discharge or 7 days post-procedure, whichever comes first
MACCE: All-cause mortality, peri-procedural MI ≤72 hours after index procedure, major stroke, urgent or emergent conversion to surgery or repeat procedure. VARC Device Success: Leon, et al. J Am Coll Cardiol 2011, 57:253.
TTE=transthoracic echocardiography

5. REPRISE I Key Inclusion Criteria
Age ≥70 years
Documented calcified native aortic stenosis
AVA <1.0 cm² (or AVA index <0.6 cm²/m²) plus either MPG >40 mmHg or jet velocity >4 m/s (by echocardiography)
Symptomatic aortic valve stenosis with NYHA Class ≥II
High risk for surgical AVR
STS score ≥8% or euroSCORE ≥20% or documented heart team agreement of high risk due to frailty or comorbidities
Aortic annulus size mm
23 mm valve size used in study
AVA=aortic valve area; MPG=mean pressure gradient; NYHA=New York Heart Association; STS=Society of Thoracic Surgeons

6. Study Flow at 1 Year Intent-To-Treat Population
Intent-To-Treat (N=11)
Lotus Valve Implanted (N=11)
No Lotus Valve Implanted (N=0)
30-Day Clinical Follow-Up
100% (11/11)
1-Year Clinical Follow-Up
100% (11/11)

7. Baseline Patient Characteristics REPRISE I
Patients (N=11)
Age (Years)
83.0±3.6
Gender (Female)
11/11
STS Score (%)
4.9±2.5
Logistic euroSCORE (%)
9.5±4.4
NYHA Class III or IV
5/11
Diabetes, medically treated
2/11
Hypertension, medically treated
10/11
History of coronary artery disease
History of PCI or CABG
History of cerebrovascular accident
Atrial fibrillation
CABG=coronary artery bypass graft; PCI=percutaneous coronary intervention; STS=Society of Thoracic Surgeons.
Values are mean±SD or n/N

8. Primary Endpoint — Discharge/7 Days REPRISE I
Patients
Clinical Procedural Success (per patient)
9/11
Device Success
10/11
Successful access, delivery, deployment, valve positioning, delivery system retrieval
11/11
Intended valve performancea
One valve implanted
No MACCE through discharge or 7 daysb
a: AVA >1.0 cm2 plus either a mean aortic valve gradient <20 mmHg or peak velocity <3m/sec, without moderate/ severe prosthetic valve aortic regurgitation
b: Major adverse cardiovascular or cerebrovascular events including all-cause mortality, peri-procedural MI ≤72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction
Values are mean±SD or n/N

9. REPRISE I – VARC-1 Safety Composite No New Events from 30 Days to 1 Year
Through 30 Days
VARC safety composite
3/11
MACCE
1/11
All cause mortality
0/11
Peri-procedural MI (≤72 hours)
Major stroke
Urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction
Life-threatening/disabling bleeding
2/11a
Acute kidney injury - Stage 3
Major vascular complication
1/11b
30 Days
New Events 30 – 365 Days
VARC safety composite
3/11
MACCE
1/11
All cause mortality
0/11
Peri-procedural MI (≤72 hours)
Major stroke
Urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction
Life-threatening/disabling bleeding
2/11a
Acute kidney injury - Stage 3
Major vascular complication
1/11b
a: Events at 14 days (pericardial effusion from pacemaker implant) and 20 days (GI bleed) post procedure
b: Left femoral artery dissection treated by cross-over contralateral balloon angioplasty

10. REPRISE I – Additional Outcomes Only 1 New Event From 30 Days to 1 Year
Through 30 Days
Disabling bleeding (unrelated to valve implant)
2/11
Major bleeding (unrelated to TAVR access)
Minor bleeding
Major vascular complication
1/11
Conduction disturbance requiring new pacemaker
4/11
Myocardial infarction
0/11
Minor stroke or transient ischemic attack
90 Days
New Events 30 – 365 Days
Disabling bleeding (unrelated to valve implant)
2/11
Major bleeding (unrelated to TAVR access)
Minor bleeding
3/11 1a
Major vascular complication
1/11
Conduction disturbance requiring new pacemaker
4/11
Myocardial infarction
0/11
Minor stroke or transient ischemic attack
a: Epistaxis, adjudicated as related to clopidogrel treatment, reported at 90-day visit

11. NYHA Assessment REPRISE I P=0.004 n=1 n=3 n=7 n=1 n=4 n=6 n=1 n=5 n=6
NYHA Class (Patients)
n=6
n=3
P value: Wilcoxon signed rank test for paired data

12. Mean Aortic Valve Gradient by Patient
REPRISE I
Measurement
P value
Baseline to Discharge
<0.001
Baseline to 1 Year
Discharge to 30 Days
0.06
30 Days to 90 Days
0.71
90 Days to 180 Days
0.07
180 Days to 1 Year
0.18
Mean:
53.920.9
Mean Aortic Valve Gradient (mm Hg)
Mean:
13.73.7
Mean:
11.73.0
Mean:
12.02.2
Mean:
13.93.8
Mean:
15.44.6
Baseline
Discharge
30 Days
90 Days
180 Days
1 Year
Independent Core Lab Adjudication
P values: Repeated measures and random effects ANOVA model

13. Independent Core Lab Adjudication
Effective Orifice Area by Patient
REPRISE I
Mean:
1.50.2
Mean:
1.6±0.1
Mean:
1.6±0.2
Mean:
1.6±0.2
Mean:
1.5±0.2
Aortic Valve Area (cm2)
Measurement
P value
Baseline to Discharge
<0.001
Baseline to 1 Year
Discharge to 30 Days
0.08
30 Days to 90 Days
0.21
90 Days to 180 Days
0.28
180 Days to 1 Year
0.43
Mean:
0.70.2
Baseline
Discharge
30 Days
90 Days
180 Days
1 Year
Independent Core Lab Adjudication
P values: Repeated measures and random effects ANOVA model

14. No Moderate / Severe AR by Independent Adjudication
REPRISE 1 – Aortic Regurgitation Transthoracic Echocardiography 20 40 60 80
100
n=1
n=1
n=1
n=2
n=1
Severe
n=1
Moderate
% of Patients
Mild
Trivial
None
n=8
n=10
n=8
n=10
Paravalvular
Central
Paravalvular
Central
Discharge
1 Year
No Moderate / Severe AR by Independent Adjudication

15. REPRISE I Summary of Data Through 1 Year
MACCE: 1/11
— Major stroke, post-procedure
VARC-1 1-year safety composite: 3/11
2 disabling bleeds (not related to valve implant) (<30 days)
1 major vascular complication (femoral dissection) (Day 0)
​No deaths or myocardial infarctions
Significant improvements in NYHA class and TTE measures
​No moderate or severe aortic regurgitation
10/11 patients with no or trivial AR, 1/11 with mild AR
Only 1 event (minor bleeding at 90 days) from 30 days to 1 year

16. REPRISE I Conclusions Through 1 Year
Lotus Valve can be positioned precisely & successfully with minimal aortic regurgitation after placement
The safety & efficacy of the Lotus Valve are sustained out to 1 year
Clinical event rates are very low after the first 30 days
Good immediate post-procedure results bode well for the long term
The ongoing REPRISE II Study is expected to confirm these data in a larger patient population.
30-Day results for the first 60 patients in REPRISE II will be presented in today’s Hot Line Session: First-in-man in valvular heart disease, 15:40 to 16:40, Room 241

17. Thank You!