Eberhard Grube MD, FACC, FSCAI Heart Center University Bonn, Germany

Stanford University, Palo Alto, California, USA

In Perspective: Impact of new TAVI Devices on

TAVI Complications

X Congreso Colegio Colombiano Santiago de Cali, 29-31 Octubre des 2014

Eberhard Grube, MD

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, OF Direct Flow: C, SB, AB Mitralign: AB, SB, E Boston Scientific: C, SB, AB Cordis: AB Abbott Vascular: AB Valtech: E, SB, In Seal Medical: SB, E Claret: SB Keystone, SB Key G – Grant and or Research Support E – Equity Interests S – Salary, AB – Advisory Board C – Consulting fees, Honoraria R – Royalty Income I – Intellectual Property Rights SB – Speaker’s Bureau O – Ownership OF – Other Financial Benefits‘

• Old…very old…

• Frail…very frail

• Lots of co-morbidities…

‒ Prior CABG (poor LV function)

‒ CKD

‒ Severe COPD

‒ PVD

‒ Chronic AF

‒ Cancer in remission

The typical TAVI Patient

…..but still enjoying life.!

Top 33% Surgical Risk STS ≥ 4

Top 7% Surgical Risk STS > 8

Surgical Aortic Valve Replacements 70-90,000 yearly Inoperable 20-50K

Extreme Risk

“Cohort C” Two-thirds of patients will remain optimal surgical candidates???

STS PROM < 4%

30-Day Mortality < 2-4%

Identifying the Right Patients

PARTNER IIA SURTAVI

Intermediate

≈ 26%

PAR

TNE

R B

C

oreV

alve

Ext

rem

e R

isk

PAR

TNE

R A

C

oreV

alve

Hig

h R

isk

Futil

ity

The Clinical Indications for TAVI have expanded to "Lower-Risk" Patients

and is Justified!

The Beauty of Roses! Where are the Thorns?

2nd Post Implant Day 87 years

Remaining TAVI Challenges

Sizing Post-implant intervention

(dilation, snare) Depth of Implant

Depth of Implant Balloon strategies

AR and PVL

Conduction Disturbances

Procedure/Technique Technology

Frame design Advanced Sealing

Positioning, Recapture

Frame design Stable deployment

with recapture

Balloon strategies Anti-coagulation mgmt

Stroke

Embolic Protection

Vascular Complications

Alternative Access Lower profile

Access specific delivery Coatings

Non – Circular Annulus +

Irregular Calcification =

PVL

Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations

Paravalvular Leak (PVL)

Impact of postprocedural AR≥grade 2 on 1-year mortality rate according to the presence of AR≥grade 2 at baseline.

FRANCE 2 REGISTRY

Van Belle E et al. Circulation. 2014;129:1415-1427

Strokes after TAVI

Many Strokes Occur Periprocedurally

P. Kahlert et al, Circulation 2012;126:1245-1255

Vascular Complications

Iliofemoral CT Angiogram

Tortuosity, Calcium, Marginal CSA

< OD 18Fr 6.93 mm

I.D. O.D. O.D.

expanded

Edwards 16 F (5,3 mm) 20 F (6,7 mm) 26 F (8,9 mm)

Edwards 18 F (5,9 mm) 21,6F (7,2 mm) 26 F (8,9 mm)

Edwards 20 F (6,6 mm) 24 F (8,0 mm) 30 F (9,9 mm)

Solopath 21 F 24 F

Solopath 19 F 22 F

St. Jude 18 F 21,5 F

Cook 18 F 21,8 F

Vascular Access – Sheat Sizes

Anatomical Considerations Conduction abnormalities are not atypical following AVR due to the anatomical proximity of the aortic valve to the conduction system

– Distance from the non-coronary cusp to the HIS bundle has been measured to be 6.3 ± 2.4 mm.

Modified from Tawara. Igawa et. al, Jap Circ 2009

Gutierrez et al. Am Heart J 2009, (N=33)

Implant Depth Impacts Conduction Disturbances

• A lower (ventricular) position of the valve relative to the hinge point of the anterior mitral leaflet was associated with a higher incidence of new LBBB (35% vs. 0%, P = .029).

Implanted Below → 35% of patients developed LBBB

Hinge Point of the Anterior Mitral Valve

Implanted Above → 0% of patients developed LBBB

Explanted Edwards Images courtesy of Dr Augusto Pichard

THV Degeneration Degenerated Stenotic Sapien Heart Valve Prosthesis

Many New CE Mark Valves during last months

Several new TF Valves received CE Mark in last 6-12 months

Portico

Symetis Lotus

Sapien S3

Jena

Direct Flow

CV Evolut R

Lotus™ Valve System Components and Function

Bovine Pericardium proven long-term material

Locking Mechanism

Adaptive Seal Conforms to irregular

anatomical surfaces and minimizes paravalvular leaks

Nitinol Frame designed for strength,

flexibility, repositioning and retrieval

Center Marker Aids precise positioning

Lotus Valve System: Fully Deployed

REPRISE II Aortic Regurgitation Paravalvular Aortic Regurgitation Over Time

Perc

ent

of

Eval

uab

le E

cho

card

iogr

ams 100% -

80% -

60% -

40% -

20% -

0% - Baseline (n=112)

None

Trace

Mild

Moderate

Severe

2.0

3 Months (n=102)

6 Months (n=89)

1.0 2.7

12.5

30 Days (n=103)

2.1

Discharge/7d (n=110)

Paravalvular

No severe paravalvular aortic regurgitation post-implantation

1.1

REPRISE II Trial 6-Month Safety Results

Patients (N=119*)

All-cause mortality (Primary Safety Endpoint at 30 days)

8.4% (10/119)

Disabling stroke† 3.4% (4/119)

Myocardial infarction 3.4% (4/119)

Life-threatening or disabling bleeding 5.0% (6/119)

Major vascular complication 2.5% (3/119)

New permanent pacemaker 29.4% (35/119)

LVOT overstretch ≥10% 57.1% (20/35)

Annulus overstretch ≥10% 40.0% (14/35)

New Edwards TAVR Systems

Balloon-expandable Sapien 3

Self-expanding Centera

Centera Valve fully deployed

Portico and CoreValve Design Comparison

25 mm Portico1 26 mm CoreValve2

1. St. Jude Medical Data on File. 2. Medtronic, CoreValve brochure, PN090401 V1 April 2007

Flared annulus design Non-flared annulus design

The annulus section of the Portico stent is not flared when compared to the flared annulus section of the CoreValve. Designed to minimize the risk of interfering with the conduction system and mitral valve apparatus.

EnVeo R with InLine Sheath Reduced Maximum Diameter by 4-12Fr

18FR

22 Fr (OD)

CoreValve w/ 18Fr

Cook Sheath

1 Hayashida K., Lefevre T., Chevalier B.; et al. Transfemoral Aortic Valve Implantation; New Criteria to Predict Vascular Complications, J Am Coll Cardiol Intv 4 2011 851-858

Current

CoreValve Evolut R

w/ InLine Sheath

Future

26.7–29.7Fr (OD)

16FR

Sapien XT w/

Edwards e-Sheath

18 Fr (OD)

The Direct Flow Medical® Transcatheter Aortic Valve

Minimize Risk of Aortic Regurgitation

• Double-ring design conforms to anatomy for a better seal

Optimization of Positioning

• Full hemodynamic assessment before final detachment

• Repositionable

• Fully retrievable

Improved TAVR Procedure

• Flexible, low profile delivery system

• Fully competent during positioning

• No post dilatation or rapid pacing

Positioning wires

Bovine pericardial leaflets

Investigational device not for sale in or outside the United

Conformable cuff design and precise positioning maximizes sealing to prevent PV leaks 40

Pre 6 months 18 months

Pre 6 months 18 months

Direct Flow Medical

Initial US Trial Results Consistent with DISCOVER Low Complication Rates and Nearly No AR

DISCOVER 30 Day – J. Schofer. PCR 2013; SALUS 30 Day – M. Tuzcu. PCR 2014

*

*PPM rate decreased after improved implant technique

ACURATE TF™ Aortic Bioprosthesis

LOWER CROWN

Minimal LV protrusion Low risk of conduction defects

UPPER CROWN

Supra-annular anchoring Stable positioning

Tactile feedback

STABILIZATION ARCHES

SELF-EXPANDING NITINOL

Conforms to native anatomy 3 sizes: 21mm to 27mm

PERICARDIAL LEAFLETS

Porcine pericardium Lower profile

PERICARDIAL SKIRT

Inner & outer skirt acts as seal to prevent PVL

Symetis Acurate Valve: Fully Deployed

Performance

Baseline 30D

n 89 82

Mean gradient (mmHg) 43.6 ± 17.1 8.0 ± 2.9

Mean AVA/EOA (cm2) 0.7 ± 0.2 1.8 ± 0.3

PVL ≤ Grade 1 (none to mild) *n/%+ n/a 78 / 95.1

PVL Grade 2 (moderate) [n/%] n/a 4 / 4.9

PVL > Grade 2 [n/%] n/a 0 / 0.0

NYHA Class III/IV [n/%] 84 / 94.4 8 / 9.8

Procedural Success TAVI Clinical Trials and Registries

100,0 99,3 97,8 96,9 95,9 93,8 93,0 92,0

50

70

90

% P

roce

du

ral S

ucc

ess

LOTUS REPRISE II1

SAPIEN 32 CoreValve ADVANCE3

FRANCE 24 CHOICE SAPIEN XT5

SOURCE6 Direct Flow

DISCOVER7

TVT8 CHOICE CoreValve9

N=120 N=150 N=1050 N=3195 N=121 N=1038 N=100 N=7710 N=120

Results from different studies not directly comparable. Information provided for educational purpose only.

24,2

16,9

14,2

11,5 9,0

4,0 3,4 1,7

0,6 0

5

10

15

20

25

30

% P

atie

nts

wit

h M

od

/Sev

ere

PV

L

SAPIEN XT

PARTNER II, Inop1

SAPIEN PARTNER II Inop1

CoreValve ADVANCE2

CoreValve Extreme

Risk3

CoreValve High Risk4

Portico

CE Study5

SAPIEN 36

Direct Flow

DISCOVER7

LOTUS REPRISE II & EXT8

N=236 N=225 N=639 N=418 N=390 N=75 N=150 N=100 N=250 1Leon M, ACC 2013, 2Linke A, PCR 2014. 3Popma J, JACC 2014; 63(19): 1972-81, 4Adams D, N Engl J Med 2014; 370: 1790-98. 5Manoharan, et al. TCT 2014. 6Webb J, EuroPCR 2014. 7Schofer, JACC 2013. 8Ian Meredith, London Valves 2014. Results from different studies not directly comparable. Information provided for educational purpose only

1 Month Moderate & Severe PVL Echo Core Lab Adjudicated Clinical Trials

29,2

20,9

9,4

6,1 4,3

0 0

5

10

15

20

25

30

3512-mo Mod/Severe PVL rate

Adverse Clinical Outcomes TAVI Clinical Trials

PARTNER II SAPIEN XT5

PARTNER II SAPIEN5

CoreValve ADVANCE1

CoreValve High Risk3

CoreValve Ext Risk4

LOTUS REPRISE II2

STS Score:

10.3 11 5.3 7.3 10.3 7.1

N: 284 276 1015 394 489 120

% o

f Pa

tien

ts

1Linke A, PCR 2014., 2Ian Meredith, TCT 2014 3Adams D, N Engl J Med 2014, 4Popma J, JACC 2014, 5Leon M, ACC 2013. Results from different studies not directly comparable. Information provided for educational purpose only

35

30,9

17,7 17,5 15,5 14,8

13,6 13 12,6 10 9,5 8,8

7,3 7 4,5 4 3

0

5

10

15

20

25

30

35

40

A B C D E F G H I J K L M N O P Q

Moderate+Severe % PVL

Post-implant/30 Day PVL Mixed (Edwards + CoreValve) Real World Registries

*PVL rates from evaluable data. Results from different studies not directly comparable. Information provided for educational purpose only

Pati

ents

* (%

)

A: Hayashida1, N=260 B: Buchanan2, N=305 C: Gilard3, N=3195 D: Abdel Wahab4, N=690 E: Lange5, N=420 F: Van Belle6, N=2769 G: Moat7, N=870 H: Gotzmann8, N=145 I: Tamburino9, N=218 J: Al-Lamee10, N=1627 K: Eltchaninoff11, N=244 L: Wenawaser12, N=682 M: Hamm13, N=2694 N: Puls14, N=180 O: Stahli15, N=130 P: Fraccaro16, N=384 Q: Stohr17, N=175

1Hayashida, et al. J of Am Coll of Cardiol 2012;59(6)., 2Buchanan, et al. EuroIntervention 2011;7:556-563., 3Gilard, et al. N Engl J Med 2012;366:1705-15., 4Abdel-Wahab, et al. Heart 2011;97:899-906., 5Lange, et al. JACC Jan 2012:280-7., 6Van Belle, et al. Circulation 2014;129:1415-1427., 7Moat, et al. J of Am Coll of Cardiol 2011;58(20)., 8Gotzmann, et al. Am Heart J 2011;162:238-245., 9Tamburino, et al. Am J of Cardiol 2012 May 15;109(10):1487-1493., 10Al-Lamee, et al. AJC 2013., 11Eltchaninoff, et al. Eur Heart J 2011;32:191-197., 12Wenaweser, et al. EuroIntervention 2014; 9-online published-ahead-of-print April 2014., 13Hamm, et al. doi:10.1093/eurheartj/eht381., 14Puls, et al. Clin Res Cardiol 2012;101:553-563., 15Stahli, et al. J Invasive Cardiol 2011;23:307-312., 16Fraccaro, et al. Circulation 2012;5:253-260., 17Stohr, et al. Coronary Artery Disease 2011;22:595-600.

Valve in Valve Deployments TAVI Clinical Trials and Registries

1,1 0,8

3,7

2,5 2,2

1,4

2,9

4,0

2,9

5,8

3,5 3,9

0,0 0

5

% V

alve

in V

alve

Dep

loym

en

t

PAR

TNER

II 4

CH

OIC

E1

PAR

TNER

II 4

PAR

TNER

I (A

and

B) 8

SOU

RC

E9

FRA

NC

E 25

TVT R

egistry6

AD

VA

NC

E2

Co

reValve

Extreme R

isk7

CH

OIC

E1

FRA

NC

E 25

Portico

CE

Trial 3

REP

RISE

II & EX

T1

0

284 117 276 2554 1387 2107 7710 996 489 121 1043 102 250

Results from different studies not directly comparable. Information provided for educational purpose only. 1 Abdel-Wahab, JAMA 2014. , 2Linke, et al. EHJ, March 2014., 3Makkar, Presented at TVT 2014. 4Leon, et al. TCTMD online. 5Van Belle, et al. Circulation 2014. 6Mack, et al. JAMA 2013. 7Reardon, et al. J Thor and Cardiovasc Surgery 2014. 8Makkar, et al. JACC 2013., 9Thomas, et al. Circulation 2011. 10Ian Meredith, London Valves 2014

N:

CoreValve SAPIEN XT SAPIEN LOTUS Portico

Major/Disabling Stroke at 30 Days REPRISE II & Other TAVR Studies

3,2 3,0 3,8

5,0

1,2

2,3

3,9

1,7

0

2

4

6

8

10

SAPIEN XTPARTNER IIInoperable

SAPIENPARTNER IIInoperable

SAPIENPARTNER A

SAPIENPARTNER B

CoreValveADVANCE

CoreValveExtreme

Risk

CoreValveHigh Risk

LOTUSREPRISE II

Even

t R

ate

(%)

PARTNER A: Smith, et al. N Engl J Med 2011;364:2187; PARTNER B: Leon, et al. N Engl J Med 2014; 370: 1790-98; PARTNER II Inop: Martin Leon, MD at ACC 2013; CoreValve Extreme Risk: Popma J, JACC 2014; 63(19): 1972-81 REPRISE II: Meredith I et al, J Am Coll Cardiol 2014;64:1339–48; CoreValve ADVANCE: Linke A, EuroPCR 2014.

Results from different studies not directly comparable. Information provided for educational purpose only.

Page 63

CoreValve Sapien XT Direct Flow Lotus Portico Symetis Sapien 3 Centera Evolut R

Valve Med

Frame Material

Nitinol

Cobalt chromium

Polyester fabric

Braided Nitinol

Nitinol Nitinol Cobalt chromium

Nitinol Nitinol Nitinol

Tissue Porcine pericardial inner skirt

Bovine Pericardial inner skirt

Bovine Pericardial

Bovine Pericardial with PET

outer skirt

Bovine Pericard-ial inner

skirt

Porcine Pericard-ial inner

and outer skirt

Bovine Pericard-

ial Polyester outer skirt

Bovine Pericard-ial inner

skirt

Porcine pericardial inner skirt

(outer skirt in development)

Bovine Leaflet

Valve Design

Supra-annular

Intra-annular

Intra-annular

Intra-annular

Intra-annular

Intra-annular

Intra-annular

Intra-annular

Supra-annular

Intra-annular

Vascular Access

ID: 18Fr OD: 21.7Fr

ID: 18-22Fr OD: 21-

30Fr (16Fr

eSheath)

ID: 18FR OD:

21.7FR

ID: ? OD: 21.7Fr

ID: 18Fr OD:

21.7Fr

ID: 18Fr OD:

21.7mm

ID: 14FR eSheath

OD: 26FR *

ID: 14FR eSheath

OD: 22FR *

ID: 18Fr OD: 18Fr

(14Fr Inline Sheath)

ID: 12FR OD: 14FR

Other AOA® ThermaFix® Anti-Ca++ Recapture

Recapture Linx™ Recapture

None Therma- Fix

Future GLX

Therma-Fix

Future GLX

Recapture

AOA® Recapture

Modular approach

Improving Clinical Outcomes: Competitive Landscape Contd.

Study, Sample Size

US Pivotal Extreme Risk

N=489

PARTNER IIB N=284

DISCOVER CE N=100

(evaluable cohort N=75)

Reprise II N=120

Portico CE N=83

Acurate CE N=89 TF

CE Pivotal N=150

FIM N=15

30 Day Survival

91.6% 96.5% 98.7% 95.8% 96.4% 96.6% 94.7% 87%

Maj. Vasc Comp

8.2% 9.6% 2.7% 2.5% 6% 3.4% 6% NR

PPM Rate 21.6% 6.4% 16% 28.6% 10.8% 9% 13.3% 27%

PVL 41.5% mild,

11.4% mod/severe

75.9% trace/mild,

24.2% mod/severe

28.4% mild, 1.4% mod

20.7% trace/mild,

1.0% moderate

65% mild, 5% mod.

4.9% mod 24.1% mild, 3.4% mod

69% mild, 8% mod

Stroke 2.3% major 3.2%

disabling 2.7% major 1.7% disab. 2.4% major 2.2% major 2.7% NR

Coronary Occlusions

0% NR NR 0.8% NR NR 0% NR

Annulus Rupture

0.2% NR NR NR NR NR NR NR

MI 1.2% 1.8% 1.3% 3.3% 1.2% 0% 1.3% NR

Improving Clinical Outcomes: Competitive Landscape Contd.

CoreValve Sapien XT Sapien 3 Centera Portico Lotus Symetis Direct Flow

The Future

Future Concepts

• A fully optimized TAVR system which addresses current limitations may require a radical design change ….

• such as “Inside – Out” leaflet mounting or temporarily dissociating the support frame from the valve component

FOLDAX™ HEART VALVE TECHNOLOGY

14F delivery profile available

”Stressless” tissue loading

Allows use of bovine pericardium

Fully repositionable & retrievable

Valve Medical Device Components

1. Nitinol self-expanding frame module inserted in optimal annular location

2. Valve module is reconstituted in ascending Ao

3. Valve module is docked to frame

Assembled Device Frame Module Valve Module

Frame and Valve Module Docking and Locking

Polymer Coating

Para-valvular leak prevention

• Two-layer polymer coat • External hydrogel-based layer • Frame stored dry • Following implantation, the

hydrogel swells outwards (extended “seal zone“)

10 X

Thank you very much for Your Attention!