the lotus valve, the latest developments and future aspects · • novel tri-fold seam is designed...

The Lotus Valve, The Latest Developments and Future Aspects

Professor Jan Harnek MD PhD FESC

Lund University

Sweden

Potential Conflicts of Interest

Speaker’s name: Jan Harnek MD PhD

[email protected]

DISCLOSURE INFORMATION:

Consulting within the last 24 months

Full-time Lotus Proctor for Boston Scientific

SH-148709-AO Oct2016

Aortic Stenosis

Pathology

Normal

Degenerative

Calcified Bicuspid Rheumatic

SH-148709-AO Oct2016

Aortic Stenosis:

Changing Epidemiology

Normal

Degenerative

Calcified Bicuspid Rheumatic

X

SH-148709-AO Oct2016

0

2

4

6

8

10

12

14

<45 45-54 55-64 65-74 >75

Increasing Prevalence of Valvular Heart Disease in the Elderly

Pre

va

len

ce

of m

od

or

se

ve

re V

HD

(%

)

All valve disease

Mitral valve disease

Aortic valve disease

0

2

4

6

8

10

12

14

<45 45-54 55-64 65-74 >75

Olmsted County, MN

Nkomo VT at al. Lancet 2006;368:1005-1011

Population-based

Studies

Incidence of Aortic Stenosis

Natural History of Aortic Stenosis

SH-148709-AO Oct2016

AO-Heart Valves “History”

• Concept: M. Edwards engineer and A. Starr MD 1958

• 20 Sept 1960 first surgical implant Univ. of Oregon

• Numerous valves biological and mechanical

• Numerous annuloplasty devices

• H. Rud-Andersen MD 1989 First percutaneous valve

• A. Cribier MD 1992

• First TAVR 2002 by Cribier

Henning Rud Andersen

Edwards and Strarr

© 2016 Boston Scientific Corporation or its affiliates. All rights reserved.

Lotus Valve Timeline

FIM

23mm & 27mm

1st Lotus Implant

REPRISE I REPRISE II

REPRISE III

Transfemoral

Direct aortic

2003 2007 2011 2012 2013 2014 2015 2016

SAFARI2

SAFARI

25mm

SH-392012-AA MAY 2016

LOTUS Edge™* Valve System

Design Goals

Bovine Pericardium

Proven long-term

material

One View Locking

Additional radiopaque

markers enable operator to

confirm locking in 1 view

Adaptive Seal**

Minimizes paravalvular

leak by conforming to

irregular anatomical

surfaces

Braided Nitinol Frame

Designed for strength,

flexibility, and ability to

retrieve, reposition, and

redeploy

**Meredith, I. REPRISE II. TCT 2015

Depth Guard™

To minimize LVOT

interaction to reduce

PPM

Flexible Catheter

Reduced proximal profile

and more flexibility

to improve trackability

New to LOTUS Edge™* *This device is pending CE Mark and is not available for sale.

SH-425204-AA SEPT16 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved.

Designed for Simplified Delivery

Improved vessel access with more flexible

catheter and a smaller proximal profile

3 – 4F reduction in profile of proximal

catheter compared to Lotus1

> 30% more trackable with a minimized pre-

shaped curve1

1. In bench test comparing Lotus™ Valve System versus Lotus Edge™ Valve System Profile: Edge OS Print 91040473-01 and 91047560-01. Trackability: ER11346 LOTUS Edge n=4, Lotus n=2.

LOTUS Edge™*

Lotus™


*This device is pending CE Mark and is not available for sale.

Next Generation TAVI Design Goals

iSleeve™* Expandable Sheath

14Fr design

Improved vessel access

14Fr

Enhanced flexibility

Optimizing valve deployment

Simplified locking

BOLT™ Direct Access Sheath

Reduced length

Uncoated with multiple markers

Five Valve Sizes

18mm – 29mm Annulus Size

21mm 29mm

LOTUS Edge™ * Valve System


SH-392012-AA MAY 2016


LOTUS™ Edge Valve System – Design Features

Compared to Current Lotus ™ Valve



Lotus™ LOTUS Edge™*

Delivery System Pre-shaped Flexible

Sheath 18 / 20F 14F / 15F* Q1 2017

Locking Verification Multiple views 1 view

Valve Sizes 23mm, 25mm, 27mm 23mm, 25mm, 27mm, 21mm*,

29mm* (*late 2017)

Deployment Controlled Mechanical Controlled Mechanical with Depth

Guard™

Product Box Long/Tall Flatter/Rectangular

Designed for Simplified Deployment

One View Locking

• Additional radiopaque markers allow one view locking intended to: • Minimize contrast and

radiation • Reduce procedure time

One View Locking



Depth Guard™ Technology designed to reduce LVOT interaction and lower PPM rates

• Anchors early during deployment • Minimizes depth of valve frame • Enables more predictable placement

Designed for Simplified Deployment

Depth Guard™ Deployment Technology

Annulus Annulus

Lotus™ Valve Lotus Edge™* Valve



Bell shape deployment Funnel shape deployment


Goal for Depth Guard™ Technology and

PPM Rate

+


Depth Guard™ Technology

New Deployment Technique

+

Lower PPM rate

=

Posts aligned to the annulus

Designed to reduce LVOT interaction

SH-425204-AA SEPT16


Functioning valve with no PVL after deployment

Adaptive Seal™:

Lotus ™ Valve System

Unmatched Freedom From PVL*

• Conforms to the anatomy to

create a secure seal

*As published to date. Results from different studies are not directly comparable. Information provided for educational purpose only. 1) I. Meredith, REPRISE II, TCT 2015. 2) I. Meredith, RESPRISE II, TCT 2015. 3)I. Meredith, REPRISE II EXT., PCR LV 2015. 4) PARTNER II S3: Thourani, V H, et. al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. The Lancet, April 3, 2016. www.thelancet.com. 4) S. Brecker, Core Valve ADVANCE, euroPCR 2015. 5) G. Manoharan, Core Valve Evolut R CE Study, TCT 2015. 6) G. Manoharan, Portico CE Study, TCT 2014.

Adaptive Seal


http://www.thelancet.com/

Designed for Complete Repositionability

Valve functions immediately during deployment

With complete repositioning prior to release, even after full deployment, LOTUS Edge™* allows unprecedented control, ensuring precise placement

100% R e p o s i t i o n a b l e

Precise placement

for every patient

100% D e p l o y m e n t

0% M a l p o s i t i o n i n g i n R E P R I S E T r i a l s 1 - 3 Ɨ

Repositionability for

managing complexities

at

with

TAV-in-TAV, ectopic placement, valve migration or embolization: 1) I. Meredith, REPRISE I. TCT 2015.; 2) I. Meredith, REPRISE II. TCT 2015; 3) I. Meredith, REPRISE II EXT. PCR LV 2015.

Ɨ LOTUS Transaortic Valve studied in REPRISE trials.




Planned Valve Sizes & Treatment Range

23 mm LOTUS Edge™* Valve



Native Annulus Diameter

≥20 mm and ≤23 mm



Deployed Lotus Valve OD**

23 mm

25 mm

27 mm

Deployed Valve Height

19 mm

19 mm

19 mm


*This device is pending CE Mark and is not available for sale. **As measured by baseline diagnostic imaging

iSleeve™* Introducer

Design Goals for Expanding Access

• Ultra-thin walled expandable sheath design

• Low Profile (14F/15F) introduction and removal

• Novel Tri-Fold Seam is designed to minimize vessel trauma

• Easier expansion versus existing expandable sheaths

• Transient expansion can improve vascular closure

• Designed specifically for LOTUS Edge™*

iSleeve™* Features

*This device is pending CE Mark and is not available for sale. SH-425204-AA SEPT16 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved.


Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014 Mar 20;9(11):1264-70

REPRISE I

REPRISE II Extension

RESPOND

REPRISE III

Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes Primary Safety Endpoint: All-cause mortality at 30d

Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes Primary Endpoint: All-cause mortality at 30d & 1y

FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N~1000; Global RCT vs. comparator; 23, 25 & 27mm valve sizes Enrollment Complete

Lotus™ Clinical Program

REPRISE II

CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014; In Review

REPRISE IV and REPRISE V trials in development

REPRISE Edge Safety & Performance Study N~60; Single Arm; 23, 25 & 27mm valve sizes Primary Endpoint: Mean aortic pressure gradient at discharge


SH-148709-AO Oct2016 Page 24

Implant example of the Lotus Edge

Crossing arch

18mm BAV 23mm Edge valve Low position due to 9mm LM Top-post technique planned Very low resistance crossing arch

Initial unsheathing

a) Create a small funnel

b) Seat valve in annulus Slight backwards tension applied c) Maintain top-post at annulus Catheter angle changes more on Edge when pulling/pushing Top-post probably facilitated by BAV

Locking process

Centralize catheter Very easy to observe gaps closing NC buckle-post last to close

Final result

Good final result No partial resheath Good coronary access Trace PVL 4.5 min catheter time

SH-148709-AO Oct2016 Page 29

23mm

Borderline 23mm had moderate PVL despite repositioning Valve was exchanged for a 25mm, final result no PVL

Exchangeable 23mm Lotus Valve retrieval and exchange for 25mm Lotus Valve

25mm

SH-148709-AO Oct2016 Page 30

Repositionable

Partial: as many time as needed

Complete: only once

SH-148709-AO Oct2016 Page 31

Hemodynamic Stability

Fluoro top view of Lotus Valve

Boroscopic LVOT view of Lotus Valve

Lotus Valve Deployment in Benchtop Flow Model

SH-148709-AO Oct2016 Page 32

PARTNER Trial 1-Year Outcomes Stratified by PVL PVL is a Significant Predictor of Mortality

Multivariate Analysis – Predictors of One-Year Mortality

Kodali, et al. Eur Heart J 36 (2015): 449-456.

Variable Hazard Ratio P Value

PVL (Mild vs. None/Trace) HR=1.37 [1.14, 1.90] P<0.001

PVL (Mod/Severe vs. None/Trace) HR=2.18 [1.57, 3.02] P<0.0001

Overall Log-Rank P< 0.001

SH-148709-AO Oct2016 Page 33

PARTNER Trial 3-Year Outcomes Stratified by PVL PVL is a Significant Predictor of Mortality

Kodali, et al. N Engl J Med 366.18 (2012): 1686-1695.

Variable Hazard Ratio P Value

PVL (None/Trace vs. Mild to Severe) HR=2.11 [1.43-3.10] P<0.001

Multivariate Analysis – Predictors of Three-Year Mortality

SH-148709-AO Oct2016 Page 34

64,7

40,9 30,8

39,3 29,1 25,8 21,2

14,7

11,8

20,9

29,2 9,4

4,3

0 0

0

20

40

60

80

Portico CE Study1

SAPIEN PARTNER II2

SAPIEN XT PARTNER

II2

CoreValve ADVANCE3

CoreValve Ext Risk4

CoreValve High Risk5

DirectFlow DISCOVER6

LOTUS REPRISE II/II

EXT7

STS Score: 6.2 11.0 10.3 5.3 10.3 7.3 9.7 6.5

N: 34 186 199 745 330 295 66 163

12-Month Moderate & Severe PVL TAVI Clinical Trials

% P

atie

nts

wit

h M

od

/Sev

ere

PV

L

Mod/Severe PVL Mild PVL

12-Month

Results from different studies are not directly comparable. Information provided for educational purpose only. 1Manoharan G, TCT 2014. 2Leon M, ACC 2013. 3Linke A, Eur Heart J 2014. 4Popma J, JACC 2014. 5Adams D, N Engl J Med 2014. 6Lefevre T, JACC:CI 2016. 7Meredith I, PCR LV 2015. Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

6.1

SH-148709-AO Oct2016 Page 35

Safari2™ Guidewire Design Goals

• Enhanced wire predictability, with superior shape retention

• Streamlined device delivery through optimized rail support

• Widest guidewire choice with three curve sizes

Fluoroscopic image of the Safari Guidewire in-situ

Extra Small

Small

Large

One Length (275cm)

Graphic of Safari Guidewire positioned in the left ventricle

3 Curve Sizes:

SH-148709-AO Oct2016 Page 36

Int./Low

Risk • NOTION II

Combined Procedures

• LAAC & TAVR Pilot

TAVR

vs SAVR • MRI Study

• 4D MRI assessment

Real World • Wohrle Registry • LEAR (LOTUS

Edge)

Lotus vs

Other TAVI* • Monash Exp. • MRI Study • LV Mechanics • Hemodynamic Eval. • Wohrle Registry

BSC Core Trials • REPRISE I • REPRISE II • REPRISE II EXT • REPRISE III • REPRISE JAPAN • RESPOND • REPRISE CAS • REPRISE IV & V

Lotus Ongoing and Upcoming Core Trials and Investigator-Sponsored Research for the Lotus Valve

Boston Scientific is not responsible for the collection, analysis or reporting of the investigator-sponsored research output which is the sole responsibility of the investigators. Boston Scientific’s involvement in investigator-sponsored research is limited to providing financial support for research that advances medical and scientific knowledge about our products. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

*TAVR includes: CoreValve, Evolut-R, S3, and SAPIEN XT

SH-148709-AO Oct2016 Page 37

• Bicuspids

• Horizontals

• LVOT calcifications

• Septal bulge

• No need for BAV or Rapid pacing

• Subclavian and Trans Aortic

• Lotus in failed surgical aortic valves

• Compassionate use and “off label” in the Mitral position: MAC; failed rings and surgical mitral valves

LOTUS “Probably Today the Best Valve in the World”

SH-148709-AO Oct2016 Page 38

Bicuspid Anatomy Verification & Lotus Valve Sizing

* Echo Core Laboratory: Cardialysis Core Laboratory, Rotterdam, the Netherlands; Core Lab Chief: Osama I.I. Soliman, MD, PhD, FACC, FESC Valve classification schematic modified from: Sievers HH, Schnidtke C. J Thorac Cardiovasc Surg 2007;133:1226-33.

• Bicuspid aortic valve anatomy

• Preliminary identification was site-reported

• Validation performed by echocardiography core laboratory* and via systematic review of CT angiograms at Erasmus Medical Centre

• Valve sizing was determined using valve matrix

• Final decision was at the discretion of the operator

0 raphe

Type 0 1 raphe

L-R R-N N-L

Type 1 2 raphes L-R / R-N

Type 2

SH-148709-AO Oct2016 Page 39

Intent-To-Treat Analysis N=1014

No Lotus valve implanted

n=18

Bicuspid Aortic Valve n=31 (3.1%)

As-Treated Analysis n=996

RESPOND Bicuspid Analysis: Patient Disposition

Non-bicuspid Aortic Valve

n=965 (96.9%)

Bicuspid valve type

Type 0 14.8%

Type 1 81.5%

Type 2 3.7%

Presented by Blackman, PCR 2016.

SH-148709-AO Oct2016 Page 40

30-Day Outcomes P-value

All-cause mortality and disabling stroke 6.5% 4.0% 0.361

All-cause mortality 3.2% 2.2% 0.509

Cardiovascular mortality 3.2% 2.0% 0.476

All stroke 3.2% 3.0% 1.000

Disabling stroke 3.2% 2.2% 0.509

Major vascular complications 6.5% 2.8% 0.231

Life-threatening or disabling bleeding 6.5% 2.1% 0.150

Myocardial infarction (>72h post-procedure) 0.0% 0.6% 1.000

Acute kidney injury (Stage 2 or 3) 3.2% 2.5% 0.555

Newly implanted permanent pacemaker 19.4% 30.4% 0.188

Bicuspid N=31

Non-bicuspid N=965

Correct positioning of a single prosthetic valve in the proper anatomical location

100.0%

99.8%

Repositioning success (if attempted) 90.0% (9/10) 96.0% (287/299)

P-value obtained by Fisher Exact test or Chi Square test, as appropriate.

RESPOND Bicuspid Analysis: Principal Safety Results As-treated population (N=996)


SH-148709-AO Oct2016 Page 41

Per

cen

tage

of

Eval

uab

le E

cho

card

iogr

ams

N=29 N=905

None

Trace Mild

Moderate Severe

P=NS

Core lab adjudicated data

Bicuspid Non-bicuspid

RESPOND Bicuspid Analysis: PVL at Discharge As-treated population (N=996)


LOTUS In Bicuspids

None or trace PVL´s !

SH-148709-AO Oct2016 Page 43

Lotus in Horizontals > 60 degrees

None or trace of PVL !

LOTUS when Calcium into the LVOT

Annular rupture never seen!

In ~ 7000 implants worldwide.

None or trace of PVL!

Lotus if Septal Bulge

No embolization's!

SH-148709-AO Oct2016 Page 46

RESPOND Balloon Valvuloplasty Analysis (N=500) Evaluation of 30-d outcomes with or without BAV; BAV at discretion of the operator

Variable BAV

(N=283) No BAV (N=201) P value

Absence of procedural

mortality 0.4% (1/283) 0% (0/201) 1.00*

Correct positioning of a single

valve in proper location 99.6% (278/279) 99.5% (196/197) 1.00*

Repositioning success, if

attempted 100.0% (61/61) 97.1% (68/70) 0.50*

Valve retrieval success, if

attempted 90.9% (10/11) 100.0% (8/8) 1.00*

Mean aortic gradient

<20mmHg 96.1% (249/259) 97.9% (186/190) 0.29

Peak velocity <3 m/s 95.8% (248/259) 97.9% (186/190) 0.21

No moderate/severe PVL 99.2% (260/262) 100.0% (192/192) 0.51*

Values are percent (n/N) or mean ± standard deviation (n). Site-reported data. *P value from 2-sided Fisher’s test; otherwise from Chi-square test for categorical values and t test for continuous variables. Presented by Van Mieghem ACC 2016. Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

No significant difference between groups in device success/performance

SH-148709-AO Oct2016 Page 47

Perc

ent

of

Eval

uab

le

Ech

oca

rdio

gram

s

BAV (N=262)

No BAV (N=192)

None

Trace

Mild

Moderate

Severe

79,8 88,0

14,5 8,3

0

20

40

60

80

100

P=0.02

Significantly more PVL in the BAV group at hospital discharge

Core lab adjudicated data. Presented by Van Mieghem ACC 2016.

RESPOND Balloon Valvuloplasty Analysis (N=500) Evaluation of 30-d outcomes with or without BAV; BAV at discretion of the operator

5.0

0.8 3.6

SH-148709-AO Oct2016 Page 48

Clinical Outcomes % (n/29)

All-cause mortality 0%

Cardiovascular Mortality 0%

All Stroke 3.4% (1)

Disabling Stroke 0%

LT/Disabling bleeding 0%

Major Vascular Complications 3.4% (1)

AKIN (Stage 2/3) 3.4% (1)

New PPM 17.2% (5)

Bailout valve-in-valve 0%

29 Patients with severe aortic stenosis, increased operative risk, and considered

unsuitable for TF access

79 ± 7.5 years, 82.8% male

Baseline STS score: 7.7 ± 8.7

Lotus Subclavian Access Study

Presented by Petronio, PCR 2016.

100% successful valve deployment

0

0,4

0,8

1,2

1,6

2

0

20

40

60

80

100

EOA

, cm2

Mea

n g

rad

ien

t, m

mH

g

Baseline Post procedure

37.6 ± 13.3

0.8 ± 0.2 12.0 ± 5.2

1.8 ± 0.6

P<0.001 P<0.001

0

20

40

60

80

100

14% 23mm

34% 25mm

52% 27mm

79%

21%

Pati

ents

, %

100% none/mild PVL post-procedure

Post procedure PVL

None

Mild

Mod

Severe

SH-148709-AO Oct2016 Page 49

Clinical Outcomes % (n/29)

All-cause mortality 0%

Cardiovascular Mortality 0%

All Stroke 3.4% (1)

Disabling Stroke 0%

LT/Disabling bleeding 0%

Major Vascular Complications 3.4% (1)

AKIN (Stage 2/3) 3.4% (1)

New PPM 17.2% (5)

Bailout valve-in-valve 0%

29 Patients with severe aortic stenosis, increased operative risk, and considered

unsuitable for TF access

79 ± 7.5 years, 82.8% male

Baseline STS score: 7.7 ± 8.7

Lotus Subclavian Access Study

Presented by Petronio, PCR 2016.

100% successful valve deployment

0

0,4

0,8

1,2

1,6

2

0

20

40

60

80

100

EOA

, cm2

Mea

n g

rad

ien

t, m

mH

g

Baseline Post procedure

37.6 ± 13.3

0.8 ± 0.2 12.0 ± 5.2

1.8 ± 0.6

P<0.001 P<0.001

0

20

40

60

80

100

14% 23mm

34% 25mm

52% 27mm

79%

21%

Pati

ents

, %

100% none/mild PVL post-procedure

Post procedure PVL

None

Mild

Mod

Severe

Lotus - Trans Aortic Access

Direct Aortic / Trans Aortic

Lotus in Failed Surgical Aortic Valves

21 Mitroflow ID 17.3 mm, 25 Mitroflow; ID 21 mm; CT ID 24.5 mm

Distance to LCA and RCA 6 and 8 mm

In Hancock II, 23mm; ID 20.5mm

23 Lotus

23 Lotus

25 Lotus

Lotus Valve in Mitral Position – Remarkable Safety Compassionate use and off label

In failed surgical rings

In failed surgical valves

In MAC

SH-148709-AO Oct2016 Page 53

Where current Lotus is not recommended

Tortuosity, fatal dissection Tortuosity, could not get marker in outer

curvature reaching the arch.

SH-148709-AO Oct2016 Page 54

Summary • The Lotus System is truly fully repositionable and retrievable.

“You should expect a surgical result”

• Ease of use and safety: No Rapid pacing No BAV - pre or post implant Local anesthesia No TEE

• Early function offers hemodynamic stability “You control the procedure, not the procedure that controls you”

• Unique safety profile: Lotus in failed surgical Valves /rings Superior in horizontals Superior in bicuspids Superior in LVOT calcifications Superior if septal bulge

• Todays high PPM and delivery-system sizes are anticipated solved with the LOTUS Edge, available Q4 2016

SH-148709-AO Oct2016 Page 55

What Next

• Shorter frame height 15/16 mm

• Further system reduction 3- 4 F

• Build in cerebral protection

• Dedicated Mitral/Tricuspid replacement valves and repair devices

Predictions are difficult. Especially about the future.

SH-148709-AO Oct2016 Page 56

Thank you !

Logic will take you from A to B.

Imagination will take you everywhere.

the lotus valve, the latest developments and future aspects · • novel tri-fold seam is designed...

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