Siegburg

New TAVI Devices: More of the Same or Meaningful

Differences?

Eberhard Grube MDIntl. Heart Center Rhein – Ruhr, Essen, Germany

Hospital Oswaldo Cruz - Dante Pazzanese, São Paulo, Brazil Stanford University, Palo Alto, California, USA

ANGIOPLASTY SUMMIT-TCTAP 2010

Siegburg

Within the past 12 months, the presenter or their spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Physician Name Company/Relationship

Eberhard Grube, MD Medtronic, CoreValve: C, SB, AB, OFSadra Medical: E, C, SB, ABDirect Flow: C, SB, ABMitralign: AB, SB, EBoston Scientific: C, SB, ABBiosensors: E, SB, C, ABCordis: ABAbbott Vascular: ABCapella: SB, C, ABDevax: SB, AB,

KeyG – Grant and or Research Support E – Equity Interests S – Salary, AB – Advisory BoardC – Consulting fees, Honoraria R – Royalty Income I – Intellectual Property Rights SB – Speaker’s Bureau O – Ownership OF – Other Financial Benefits‘

Disclosure Statement of Financial Interest

Edwards~5,500 patients

CoreValve~5,500 patients

Current Generation DevicesCurrent Generation Devices

Transcatheter AVRTranscatheter AVR

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Success, but Opportunity for Improvement

• Percutaneous Aortic Valve Replacement (PAVR) has established itself as a viable therapy• Solid clinical results• Expanding number of MD’s performing PAVR

• Challenges remain with current devices• Steep, unforgiving learning curves• Difficult to place with precision• Cannot be easily repositioned for optimization• Cannot be atraumatically removed if needed• Perivalvular Leaks• Permanent Pacemaker Implant• Stroke

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Positioning is Critical

LM

Anterior Mitral Leaflet

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MDT Corevalve Positioning Challenges

• Challenging deployment in horizontal aorta

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Edwards – Positioning Challenges

Migration of valve during deployment due to escape beats

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AV-Block III° Following COREVALVE Implantation

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Mild = I Moderate = II

Severe = IIISevere + extension = IV

Annulus and LVOT Calcification Grades Correlate With AR - ‚Siegburg Score‘

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Para-Valvular Regurgitation

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POOLED* Monitored Edwards TAVIEcho AR Results

* REVIVE, REVIVAL, TRAVERCE* REVIVE, REVIVAL, TRAVERCEand PARTNER EUand PARTNER EU

32.432.417.817.8 14.514.5

21.521.5 18.518.5 25.125.1 21.621.6

37.537.5 39.539.5

41.141.1 49.849.850.850.8 52.952.9

50.050.0

33.6

14.719.622.0

27.331.1

35.0

5.95.9 0.00.01.61.64.44.46.46.49.59.510.410.4

2.90.00.50.00.00.7 1.4

Baseline 30 days 3 months 6 months 1 year 18 months 2 years

Follow Up

AR G

rade

4+

3+

2+

1+

None

AR

N=405 N=220 N=219 N=205 N=191 N=51 N=34

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Aortic regurgitation pre and post Change of regurgitation

CoreValve Siegburg ExperienceAortic Regurgitation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pre Post

4+3+2+1+0

34.6

34.6

30.9

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pre-Post

WorsenedUnchangedImproved

24.3 28.9

54.4 51.2

19.1 18.2

0.701.5

1.7

Pre Post

4+3+2+1+0

34.6

34.6

30.9

Pre-Post

24.3 28.9

54.4 51.2

19.1 18.2

Grube E, et al. Circ Cardiovasc Intervent 2008;1:167Grube E, et al. Circ Cardiovasc Intervent 2008;1:167--75.75.

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Future Aortic Valve Concepts

– Direct Flow– Sadra– AorTx – Jena Valve– HLT– ABPS PercValve– EndoTech– Ventor Embracer

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Transcatheter Valve Therapy Next Generation Devices

Sadra DirectFlow

Low profile, repositionable, Low profile, repositionable, (?) less peri(?) less peri--valvular ARvalvular AR

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Sadra Medical Lotus Valve System

Designed for optimized aortic valve replacement with a user-friendly delivery system

• Highly accurate, controlled prosthesis positioning• Self-centering

• Easy repositioning, distally or proximally• Retrievability• Minimal Perivalvular Leakage

AdaptiveTM Seal

BovinePericardium

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Lotus Valve – Accurate Positioning

• Control in the MD’s hands• Rate of deployment• Ability to pause, unsheath, re-sheath, lock, unlock • Fully repositionable, distally and proximally

• Accurate positioning facilitated by• Self-centering • Predictable locking around central marker

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Procedure – Controlled Positioning

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Clinical Experience to Date

• Clinical experience• 10 patients enrolled – July 2007 – October 2008• 6 patients implanted, 5 surviving

• Intra-procedural results• Procedure time <20 minutes• No perivalvular leaks• No migration issues

• Follow-up at 1 year to be presented• European Trial with new Device started in April 2010

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Clinical Data Summary –Enrollment/Demographics

Number of Patients EnrolledGenderAge

1080% Female84.2±5.9 years

EuroScore (n=8)STS Score (n=8)

17.3%±7.8% (9.7 - 28.9%)9.6%±6.0% (2.3 - 22.1%)

Common Pre-existing Conditions COPD, Hypertension, hyperlipidemia, CHF, PVD, mitral valve disease

Pre-op Annulus Diameter (per CT) (n=10)

21.4±1.2 mm (20.1 – 23.7)

Pre-op Mean Gradient (n=10) 55.7±15.6 mmHg (32 – 80)

Pre-op AVA 0.58±0.08 cm2 (0.4 – 0.85)

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Long Term Follow-up – Gradient

0

10

20

30

40

50

60

70

Preop Discharge 30 Days 3 months 6 months 1 year

Mea

n G

radi

ent (

mm

Hg)

Patient 1 Patient 4 Patient 5 Patient 6 Patient 8 Patient 9

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Long Term Follow-up – Valve Area

0

0.5

1

1.5

2

2.5

Preop Discharge 30 Days 3 months 6 months 1 year

Effe

ctiv

e O

rific

e Ar

ea (c

m2 )

Patient 1 Patient 4 Patient 5 Patient 6 Patient 8 Patient 9

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Lessons from First Clinical Experience

• Lotus Valve Implant function is excellent, but

opportunities identified to improve delivery system:

• Valve attachment to and release from delivery system needed to be simplified.

• Handle needed to be redesigned with ease of use a foremost consideration

• Delivery System size limited use – needed to be reduced.

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Simplified Attachment: 15 à 3 fingers

Previous 15 finger design New 3 finger design

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Redesigned Handle: 7 à 2 controls

• Fewer controls – easier to use

• Ensures correct deployment sequence

• Reduced force required to lock

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Profile Reduction: 21 à 18 Fr

• Sadra-developed thin-wall introducer enables

fully percutaneous procedure:

• Same outer diameter as Cook 18Fr

• Reinforced for excellent kink resistance

Cook 18Fr Introducer Sheath Sadra Custom Introducer Sheath

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Latest Patient Implant – April 13, 2010

26

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Timeline• Multicenter European Trial started 13.April 2010

(PI. E.Grube)• Intl. Heart Center Rhein Ruhr (E.Grube)• University Hospital Essen (R.Erbel)• Heart Center Siegburg (R.Mueller)

• First 3 Patients enrolled with excellent acute hemodynamic and angiographic results• Zero Gradient• No Aortic Insufficiency• No Pacemaker Implant• Av. Implant Time 14 Minutes

Investigational device currently in European clinical trial Not available for sale

Multilumen

Slightly Tapered, ConformablePolyester Fabric Cuff

Tri-leaflet Valve constructed of Bovine Pericardium

Position Fill Lumens (PFLs)-Used to position/reposition valve-Complete Inflation Media Exchange

Ventricular and Aortic Rings-Inflate independently so device can be repositioned-deflatable so that device can be fully retrieved

The Direct Flow Medical (DFM) Aortic Valve Prosthesis

18F System Features18F System Features

22F Design 18F Design

3 sizes matching valvuloplasty balloons

Design: Prospective, non-randomized clinical evaluation of the DFM PAV at two centers in Germany

Hamburg University Cardiovascular Center (n=25)Siegburg, Helios Heart Center (n=6)

Purpose: Determine clinical feasibility and safety of treating patients at high-risk for cardiac surgery:

• EuroSCORE ≥ 20%• Age ≥ 70• Severe aortic valve stenosis

European Feasibility Trial

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All Values Reported - TTE All Values Reported - TTE

The DFM AV ProsthesisEuropean Clinical Trial

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• Next generation TAVR devices are rapidly evolving, providing substantial benefits over the first generation devices

• Issues addressed are repositionability, risk of paravalvular leakage, profile size etc.

• Valve + platform durability still must beconclusively demonstrated!

• Once durability is established, we can expandclinical trials and indications for TAVR to most(not all) patients with severe AS!

Summary Thoughts…Summary Thoughts…Summary Thoughts…Summary Thoughts…

Transcatheter AVR

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Aortic Atheroma: High Risk

• 268 of 3404 CABG patients (8%) had• atheroma (>/= 5 mm, or mobile)• Defined by epi-aortic ultrasound1

• 15.3% of group had intra-operative stroke1

•1Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy. Stern et al. American Heart Journal Oct. 1999.

• High Risk for:Intra-operative strokeMultiple morbidityProlonged hospital stay,Death resulting from heart surgery.1

• Risk Factors for Aortic Atheroma:• > 70 years old• Diabetes Mellitus• Hyperlipidemia• Arterial hypertension• Aortic calcifications on chest X-ray• Elevated serum levels of C-reactive protein• Other inflammatory markers• Activated coagulation3

33

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Cerebral Filter ProtectionClaret

Filter in Truncus

Filter in left Carotid

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EmboliEmboli

Emboli

Emboli

Embolic Material

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Emboli

Embolic Material

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7 mm filter placed in left carotid

Claret Dual Filter

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Embrella Embolic Deflector™

• Porous membrane designed to deflect embolic debris

• Nitinol® Frame & Shaft

•Polyurethane Porous Membrane

• Heparin Coating

• 3 Radiopaque Markers

• Suture; Monofilament Nylon

38

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Embrella Case

Example

Brachiocephalic Artery

Left Common Carotid Artery

Embrella span width

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Thank you for your attention !

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Thank you

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There Is a Higher Incidence of Pacemaker Implant Associated with CoreValve

20

33 32

1923 25

0

10

20

30

40

(n=30) (n=102) (n=34) (n=91) (n=1521) (n=126)

Calvi (PACE2009)

Grube (CircInterv 2008)

Jilaihawi (AmHeart J 2009)

Rotterdam 18F EER 18F S & E

% p

atie

nts

New Permanent Pacemaker within 30 Days

Weighted average = 23%(n=1990 patients)

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5

2025

3336

5056

0

10

20

30

40

50

60

A B C D E F G

It is important to remember that pacemaker implantation may not mean pacing need

* 2 centers with < 5 implants excluded from the presentation; both centers had 0% 30-day

permanent pacemakers

% p

atie

nts

Participating CentersPhysicians’ decision to prophylactically implant play a big

role in the variability among centers

New Permanent Pacemaker within 30 Days18F Safety and Efficacy Study (n=126)

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Claret Dual Filter

44

The Device:

• Must be easy to use!• The filter device should not be present in the aorta• Catheter 6F (5F in development)• 140 micron pore size• Right radial/brachial delivery• System will accommodate variable aortic anatomy

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Claret

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Claret Dual Filter Device

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Claret Dual Filter Device

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Embrella

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Concept of EmbrellaProduct Requirements

• Separate access site from main procedure; radial or brachial artery

• Fits through a 6F sheath• Minimal orientation• Ease of use, no new techniques• Low profile• One size fits all• Deflect debris

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Brachiocephalic ArteryBrachiocephalic Artery

Left Common Carotid ArteryLeft Common Carotid Artery

RightCommon Carotid

Artery

RightCommon Carotid

Artery

Left Subclavian ArteryLeft Subclavian Artery

DescendingAorta

DescendingAorta

Ascending AortaAscending Aorta

Brachiocephalic Artery

Left Common Carotid Artery

RightCommon Carotid

Artery

Left Subclavian Artery

DescendingAorta

Ascending Aorta

Concept of EmbrellaHuman Aorta

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Embrella Case

Example

Aortic Arch

Brachiocephalic Artery

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Embrella Case

Example

Embrella Device placed in outer curve of aortic arch

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Embrella Case

Example

Passage of balloon along the Embrella Device