New TAVR devices :

PVL en Pacemaker rate problems solved

Tailored patient treatment, with a valve choice best for different anatomical features.

Unresolved issue is durability.

Direct Flow Medical® Transcatheter Aortic Valve System

Designed to minimize AR and improve outcomes • Second generation design • Non-metallic, conformable • Polymer-filled double ring frame

Controlled procedure • Precise placement via 3 positioning wires • Assess hemodynamic function prior to

release • Fully repositionable and retrievable

Safe placement • Valve fully functional throughout procedure • No rapid pacing during valve release (stable

patient) F. De Marco, DISCOVER Trial 3yr results presented at EuroPCR 2016

Delivery System - Terminology

Nosecone Valve Positioning

Wires

Inner Catheter

Outer Sheath

Guide Wire

Guide Wire Lumen

SALUS Feasibility Trial Single arm; N=30, Extreme risk

Corelab adjudicated Enrolled

DISCOVER Trial Single arm; N=100, EuroScore ≥ 20

Corelab adjudicated FU up to 5yrs (36-month FU

available) Enrolled

DISCOVER Registry Single arm; N=503

Enrolled

SALUS Pivotal Trial Randomized 2:1 (DFM vs. Sapien 3

and CoreValve Evolut R) N=648 Extreme and High Risk

Enrolling

Clinical Registry

Clinical

Direct Flow Medical Clinical Evidence Schema

F. De Marco, DISCOVER Trial 3yr results presented at EuroPCR 2016

0%

20%

40%

60%

80%

100%

0 30 60 90 120 150 180 210 240 270 300 330 360

97% (30 d) 90%

(1 yr)

92% (6 m)

Kaplan-Meier estimate

at risk: 352 190 125 Interim Analysis presented by F DeMarco

TCT2015

The DISCOVER Registry Freedom from cardiovascular mortality

F. De Marco, DISCOVER Trial 3yr results presented at EuroPCR 2016

84%

33% 32%

30% 55%

Percentage of patients showing none or trace PVL in major trials at 30

Note: Different trial designs and patient populations, not directly comparable data. Provided for educational purposes only. Sources: A. Colombo, DISCOVER Trial, PCR 2015. I. Meredith, Corevalve Evolut R CE Mark Trial, ACC 2015; A. Linke, Portico CE Study, PCR London Valves 2015; T. Rudolph, Accurate Neo TF CE Study, PCR 2015; S. Kodali, PARTNER II Sapien 3 30-day results, ACC 2015

n=81

More Than 80% of Patients Treated with the Direct Flow Medical System Show None or Trace Paravalvular AR

F. De Marco, DISCOVER Trial 3yr results presented at EuroPCR 2016

ADVANTAGES COMPAIRING TO OTHER DEVICES VERY LOW PVL RATE VERY LOW PM RATE 4% IMPLANTATION TEE GUIDED WITHOUT CONTRAST(RENAL FAILUR AT ALL TIME RETRIEVABLE AFTER HEAMODYNAMIC ASSESMENT PITTFALLS DIFFICULT LEARNING CURVE HIGHLY CACLIFIED VALVES CAN GIVE TO HIGH GRADIENTS , ESPECIALLY IN SMALL ANATOMIE LESS THAN 23 MM

Small insertion profile (13.5F)1

No rapid pacing required2

Intra-annular positioning for early valve functionality

Flexible and trackable delivery system3

pacemaker rates4 14%

Open cell frame designed to

Minimize PVL

Provide coronary access

First to innovate with fully

Portico™ Transcatheter Valve System

Where EXPERTISE MEETS SIMPLICITY

.

1.Competitive Profile Comparison_SJM-PTC-0715-0048 2. Portico IFU 3. Søndergaard L. How Portico helps solve challenging cases: Horizontal aorta & calcified annulus. Webinar March 4, 2016. 4. Linke, A. Multicentre Clinical Study Evaluating a Novel Self-expanding and Resheathable Transcatheter Aortic Valve System. PCR London Valves 2015. 5. CVPipeline * Until fully deployed

All events adjudicated by an independent Clinical Events Committee

10

43,4

9,1 8,3 8,1 0,7

1,8 1,9 1,7

0

0,5

1

1,5

2

2,5

3

0

10

20

30

40

50

BaselineN=199

DischargeN=205

30 DayN=177

6 MonthN=161

EO

A (c

m2)

Me

an

Ao

rtic

Gra

die

nt (

mm

Hg

)

Mean Aortic Gradient EOA

Presented by S. Worthley, EuroPCR 2016

Event 30 Day Rate (%) n = 222

6 Month Rate (%) n = 222

Mortality Cardiovascular mortality

8 (3.6) 8 (3.6)

20 (9.0) 14 (6.3)

Disabling (Major) stroke 7 (3.2) 9 (4.1)

New pacemaker implantation 30 (13.5) 31 (14.0)

44,4% 44,3% 43,0%

50,5% 50,0% 54,4%

5,1% 5,7% 2,6%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

DischargeN=198

30 DayN=174

6MN=158

Pe

rce

nt Severe

Moderate

Mild

None/Trace

Portico™ TF EU 6 M Trial Results

PVL

ADVANTAGES

SMALL PROFIL,FLEXIBLE,RETRIEVABLE

NO RAPID PACING, LOW PVL RATE.5,1 %

DESADVANTAGES

PM RATE 14%

ANNULUS MAX 27 MM

SOURCE Registries

TF - Clinical Outcomes at 30 Days

0

5

10

15

20

SOURCE SOURCEXT

SOURCE3

Mortality

0

5

10

15

20

SOURCE SOURCEXT

SOURCE3

All Stroke

0

5

10

15

20

SOURCE SOURCEXT

SOURCE3

Vascular Complications

0

5

10

15

20

PARTNERA

SOURCEXT

SOURCE3

≥ Moderate PVL

Logistic EuroSCORE Analysis

Clinical Outcomes at 30 Days <10

(N=517) 10 – 20 (N=692)

>20 (N=575) p-Value

All-Cause Mortality (%) 1.6 1.2 4.2 0.001

All-Stroke (%) 1.7 1.7 0.9 0.46

Non-TF** (%) 8.3 13.7 16.2 <0.0001

Major Vascular Compl. (%) 3.9 4.6 3.5 0.66

Life-Threatening Bleeding (%) 4.5 4.8 4.9 0.95

New Permanent Pacemaker* (%) 13.8 12.0 12.4 0.59

Annular Rupture* (%) 0.2 0.1 0.2 0.98

Mod/Sev PVL** (%) 2.5 2.9 3.4 0.85

Contrast Volume (ml) 132.3 119.2 115.3 0.0002

Fluoroscopy Time (min) 14.6 13.9 13.3 0.019

Extended Ventilation (%) 6.2 5.4 5.0 0.69

Median Length of Stay (days) 7.0 8.0 9.0 <0.0001

* Site Reported KM Estimate event rates, except for ** Incidence

ADVANTAGES

VERY LOW MORTALITY AND VERY LOW STROKE RATE

EASY TO IMPLANT

DESADVANTAGES

PACING REQUIRED WITHOUT CAPTURE LOSS

CAVE LVOT CALCIFICATIONS LCC AND SEPTAL BULGE

DIFFUCULT IN VERY HORIZONTAL AORTA

CAVE PORCELAN AORTA

SH-394901-AA MAY 2016 ution: The Lotus Valve is an investigational device limited by federal law to investigational use only and not available for sale in the U.S. V.Falk, The RESPOND Study: Safety and Efficacy of a Fully Repositionable and Retrievable Aortic Valve Used in Routine Clinical Practice, Euro PCR 2016

The Lotus™ Valve

Design Goals

Controlled mechanical expansion

Valve functions early in deployment to provide hemodynamic stability

Valve is fully repositionable & retrievable throughout the entire deployment process

Adaptive seal conforms to irregular anatomic surfaces to minimize paravalvular leak

Bovine Pericardium in Nitinol in Frame

Adaptive Seal Radiopaque Marker To aid precise positioning

SH-394901-AA MAY 2016 ution: The Lotus Valve is an investigational device limited by federal law to investigational use only and not available for sale in the U.S. V.Falk, The RESPOND Study: Safety and Efficacy of a Fully Repositionable and Retrievable Aortic Valve Used in Routine Clinical Practice, Euro PCR 2016

Primary Endpoint

Based on an expected rate of 10% (based on literature review) plus a test margin of 4%. P values are from the one-sample z test; 95% CI is from Clopper-Pearson Exact Method.

SH-394901-AA MAY 2016 ution: The Lotus Valve is an investigational device limited by federal law to investigational use only and not available for sale in the U.S. V.Falk, The RESPOND Study: Safety and Efficacy of a Fully Repositionable and Retrievable Aortic Valve Used in Routine Clinical Practice, Euro PCR 2016

Key Secondary Endpoints

†Based on an expected rate of 16.5% from the FRANCE 2 registry. P values are from the one-sample z test; 95% CI is from Clopper-Pearson Exact Method

SH-394901-AA MAY 2016 ution: The Lotus Valve is an investigational device limited by federal law to investigational use only and not available for sale in the U.S. V.Falk, The RESPOND Study: Safety and Efficacy of a Fully Repositionable and Retrievable Aortic Valve Used in Routine Clinical Practice, Euro PCR 2016

Safety Endpoints at 30 Days

As-Treated population at 30 days (N=987)*

*Among patients with sufficient clinical follow-up or death, or who had an adverse event, within 30 days post-procedure.

All-cause mortality 2.2%

Cardiovascular mortality 2.0%

All stroke 3.0%

Diabling stroke 2.2%

Valve- or CHF-related repeat hospitalization 1.2%

Newly implanted permanent pacemaker 30.0%

Next Generation Boston Scientific TAVI Design Goals

N LOTUS Edge™ Valve System I Improved Deliverability Simplified Locking Lower Proximal Profile

Novel, Low Profile Sheath Expandable 14Fr Design Smaller Vessel Access

21mm 23mm 25mm 27mm 29mm

18 19 20 21 22 23 24 25 26 27 28 29

14Fr

Transfemoral

Direct aortic

BOLT™

Improved Access

• Direct aortic indication

• Direct aortic dedicated

sheath

Additional Valve Sizes (21mm and 29mm)

Annulus Size (mm) Under development, not available for sale 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.

Design Feature Current Lotus LOTUS Edge

Delivery System Pre-shaped Flexible

Sheath 18F 14F

Locking Verification Multiple views 1 view

Valve Sizes 23mm, 25mm, 27mm

21mm, 23mm, 25mm, 27mm, 29mm

CE Mark Access Indication

Transfemoral Transfemoral, Transaortic

Under development, not available for sale

LOTUS Edge Valve System Features

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.

Under development, not available for sale

COREVALVE EVOLUTE

ADVANTAGES: SUPRA-ANNULAR VALVE DESIGN VERY SUITABLE FOR V IN V TAVI AND VERY SMALL ANATOMIE. SHEATLESS FOR SMALL ANATOMIE 14FR PITTFALLS DIFFICULT IN HORIZONTAL LARGE ANNULUS PVL 6,8% PM RATE 12%