Debates in Cardiology: Most Relevant Developments, Valencia

Transcatheter Aortic Valve Implantation Update Alain Cribier, MD University of Rouen, France

Debates in Cardiology: Most Relevant Developments, Valencia, Oct 21, 2010

Severe Symptomatic Aortic Stenosis

Percent of patients undergoing intervention Cardiac reasons: Decrease Sx after treatment ÂŤ end-stage Âť cardiac disease Extra-cardiac reasons: Age, comorbidities Patient refusal

No AVR AVR

Bouma 1999

Iung 2004

EuroHeart Survey, 2004 5001 Pts in 92 centers, 25 countries Pellika 2005

Charlson 2006

Bach 2006

Spokane prelim.

Vannan Pending

Concepts of implantable prosthetic heart valves Personal challenging concept: A possible way to improve the BAV results and solve the problem of post-BAV valvular restenosis in degenerative aortic stenosis

Steps towards TAVI in Rouen  1985:

First balloon valvuloplasty for calcific AS  1994: Post-mortem studies on cadavers  1994-1998: Looking for a company interested in the project of “stented valve” Comments of experts « Major / impossible technical and anatomical issues » « Would never be approved by FDA » « Surgery covers the needs. No indication « Most stupid project ever heard ! »

Rouen, April 16, 2002 F.I.M THV implantation 57-yrs old man, cardiogenic shock, mutiple comorbidities Trans-septal approach Lessons from this FIM 1- feasibility of TAVI 2- no THV embolization 3- no coronary occlusion 4- no MR 5- no AV-heart block 6- mild AR (paravalvular) 7- optimal valvular function 8- immediate hemodynamic / clinical improvement

THV development 2008-09 A long road: Since 2007 20 Years CE Mar k from concept 2007 FIM CoreValve to real world 2005-07 2004 2002-03

2010 2002

2000

FDA Approval ?

Ew PARTNER US Pivota Post market registries CE mark commercialization International TF and TA Feasibility Studies

Edwards Lifesciences TF & TA

Feasibility Studies (antegrade) F.I.M. THV implantation

> 25 000 valves Animal implantations(sheep) (prototypes) implanted worldwide 1999

1994 1985

ÂŤ Percutaneous Valve Technology Âť

Post-mortem studies of intra-valvular stenting

F.I.M. Balloon Aortic Valvuloplasty

TAVI What is known in 2010?

Edwards-Sapien Balloon-Expandable Valve

CoreValve Self-Expandable Valve

Mechanism of THV delivery

Edwards-Sapien Balloon-Expandable Valve

CoreValve Self-Expandable Valve

Edwards Lifesciences since 2004

New valves, New delivery systems, New techniques

TF

Bovine pericardium Anti-Ca Tfx Stainless steel frame External cuff

Edwards SAPIEN™ 23mm, 26mm

TA

Tissue Valve: Bovine Pericardium with Carpentier-Edwards ThermaFix™ process

Bovine pericardial tissue contains a uniquely dense, layered collagen structure

Leaflets matched for thickness and elasticity

Surgical valves Bovine pericardium: 67% Bovine Pericardial Porcine Pericardial

Native porcine:

36%

Equine pericradium: 1%

Strong resistant tissue

Bovine pericardium valve has proven long term durability

Three Key Engineering Outputs

Proper frame height

Right level of strength to achieve circularity

Durable leaflets

Frame design

High radial force = > 92% circumferential opening A key feature for long term durability of valvular function

Circular frame opening: a key issue for durability Nitinol self-expandable stent from Laboratories Perouse (France)

JACC, 5, No5, 2008

Respect of adjoining structures Rouen: 1993-1994 Post-mortem study: Coronary ostia

Heigth: 14mm IV Septum Post-Stent 23mm Palmaz

Mitral Valve

Post-Stent Longitudinal view

Translation of post-mortem data to clinical practice LCA

IV septum

RCA Septum Hinge point Anterior mitral valve leaflet

Minimal risk of coronary occlusion Free access to LM / RCA on long term

No MR on short and long term Pace-Makers required in < 10%

Transcatheter AVR (TAVI) Edwards Clinical Pathways

PTCA TAVI

Low risk Compassionate Cases patients

8 years

High Risk Patients

2002 I-REVIVE 1 FIM, Proof of concept RECAST TRAVERCE 2003-2005 > 200 pts Small series 2 Safety/efficacy REVIVE REVIVAL 2005-2007 3 PARTNER Eu Larger series+ F.U. > 350 pts CE Mark SOURCE From 2007 4 1038 pts Post-market registries 5

Pivotal / FDA approval ?

2008-2010 1240 pts Randomized study USA

Access to the aortic valve

SUB-CLAVIAN FEMORAL

APICAL

FEMORAL

Edwards Valve

CoreValve

Careful assessment of vascular access Angiography + CT-Scan

Diameters, tortuosity, diffuse atheroma, calcifications

8.8mm

9mm 9.5mm

9.4mm

8.5mm

Preliminary assessment of access Early detection of CI to TF

3D reconstruction No information on internal lumen

CT-Scan Cross-Sections

Internal diameters and calcium distribution Crucial assessment for TF screening 10.6mm

11.8mm 7.5mm 7.5mm

7.9mm

R

L

8.5mm

7.6mm

8.23mm

7.7mm Lumen view

TAVI What is known in 2010?  Early prosthetic valve performance similar to surgical valve replacement Current indications  Decreased mortality complications  Severe and and symptomatic AS with the combination of more experience, optimal training and  High surgical risk or non operable proctoring, improved devices and procedural techniques, better patient screening and imaging modalities  Marked improvement in LV function and symptoms at mid-term patients  Still some device related events,  Patient frailty ascomplications assessed by(vascular the complete AV block) good clinical sense of a multi-

Procedural success rate COREVALVE (worldwide)

100

EDWARDS studies 95

90

85

2005

CE UR SO

EC

AS T

Va nc ou ve r RE VI VA L II RE VI VE PA RT II N ER EU TF

80

iR EV IV E/ R

FIM 2002

2009

Procedural success rate > 95%

100

EDWARDS

studies

COREVALVE

(worldwide)

95

90

85

80

FIM 2002

2005

CE

UR

SO

Va nc ou ve r RE VI VA L II RE VI VE PA RT II N ER EU TF

AS T EC iR EV IV E/ R

Eu E 2 2 C R r E L R ve IV NE VA u I V T OU o V E R S c R n RE PA Va

2009

30-day mortality and complications CoreValve

PARTNER SOURCE WEBB FRANCE N=130 N=1038 N=138 N=166

Edwards 1472 pts

Worldwide* 2300 pts,

Mortality TF

8.1%

6.3%

TA

18.8%

10.3%

8%

8.4%

18.2%

9.2%

16.9%

-

Stroke

3%

2.5%

4.2%

3.6%

3.7%

PM

3%

7%

5.4%

5.4%

29.9%

10%

7%

6.6%

6%

7.8%

Maj. Vasc.

* Eberhard Grube, Worldwide TF TAVI Experience, TCT 2010

All Cause Mortality Transfemoral Edwards, Early Studies (2003-2006) 1

75%

Freedom from Death

0.9 0.8 0.7 0.6 0.5 0.4

Partner EU Revival Revive Recast I-Revive

0.3 0.2 0.1

0

0

3

6

Months past Procedure

9

12

1 year survival: Edwards & CoreValve: Recent Registries (2009)

Edwards (SOURCE registry, 1038 pts):

TF:

81.1%

TA:

72.1%

CoreValve (Worldwide*, 1476 pts):

TF:

78% * Eberhard Grube, Worldwide TF TAVI Experience, TCT 2010

No change in EOA and gradient over time

Edwards pooled monitored studies 26

PARTNER U.S. Pivotal Trial YES

High risk patients August 2009 Surgical assessment

Inclusions completed Cohort A 24 centers, 1040 pts Femoral access evaluation YESFirst results : NO YES Y/N

NO

Cohort B Femoral access evaluation Y/N

NO

Randomization Randomization Not in Study Cohort B: Sept 23, TCT 2010

Randomization

TF THV

TF Medical Surg.

Surg.

TA Cohort A: March 2010, ACC THV vs management THV vs AVR vs AVR NON INFERIORITY of TAVI

SUPERIORITY of TAVI

50,7%

30,7%

21 septembre 2010

PERSPECTIVES Where do we go?

Improved THV and delivery systems

Upcoming registries & controled trials in specific subsets of pts

Assessment of Valve + Platform durability

THV and procedural cost / reimbursement

Expanded clinical indications ?

PERSPECTIVES ON ACCESS Angiography + CT Scan Diameter Tortuosities Calcification Trans apical

Subclavian

Edwards-SAPIEN

Transfemoral Retrograde Approach

2011 EdwardsoSapien l a r XT m e f s n (Jan 2010) a r Edwards Sapien 23mm: T % 0 a i s >7 e 22F: FA > 7 mm h t s e THV 23mm: n a l a ≅ 50% 18F: Sapien FA >u 6e mm Loc Edwards 26mm q i n h c e t e 24F: FA > 8 mm s ≅ 70% o l S c THV 26mm: E e r R P U CoreValve Medtronic D E 19F: FA > 6.5 mm C O R P E K I L T STEN THV 26mm / 29mm

18F: FA > 6 mm

≅ 70%

Subsequent generations of balloon expandable valve 2000 (FIM 2002) Percutaneous Heart Valve

Bovine pericardium Stainl. steel frame 23mm .

2003 Cribier Edwards

Equine pericardium Stainl. steel frame 23mm

2006 Edwards Sapien

Treated bovine peric Stainl. steel frame .

23 and 26mm

2009 Sapien XT

Treated bovine peric.

Cobalt Chrom. frame 23 and 26mm 20 & 29mm in evaluation

TF Introducers 24F

22F

22F, 24F

18F, 19F

Edwards Sapien XT Valve (since 2009 in EU)

• Strong frame radial force • Circumferential stent opening • Leaflets matching technology • Enhance leaflets design • Anticalcification Thermafix pro Percutaneous approach • Lower crimp profile Local anesthesia Preclose technique (ProStar) PREVAIL Trial ungoing in EU Pivotal PARTNER 2 US pending

Improved delivery systems RetroFlex 3 (Edwards Sapien)

NovaFlex (Sapien-XT) Stent like procedure

 Pure percutaneous approach 22 F  Conscious sedation 18 F

 Decreased vascular RetroFlex

NovaFlex

complications Sheath size:18F (23mm), 19F (26mm)  Discharge at Day-3

Articulated33 delivery system

Edwards Sapien XT Rouen, 38 Patients Success: 100% Conscious sedation: 100% Percutaneous: 34 (97%) AR > Grade 2: 0 Stroke: 0 Coronary occlusion: 0 Conversion to surgery: 0 Vascular complication: 1

Edwards Transapical System Refinement

? : h e r c u a t o u r f p e p a Th s u o e n a t u c r e p l a c i nsap Edwards XT Valve

A tra

ath size: 33F

Pusher: Single-handed operation 22F

Self expandable Medtronic CoreValve Generation 1 Generation 2 Generation 3 25F 21F 18F

2004-2005

From 2006

Porcine pericardium valve Nitinol stent

Generation 4 18F

2010

Improved delivery system

A new era of partnership

for patients screening, performance of the procedure and assessment of the results Radiologist

Anesthesiologist

The Heart Team

Echocardiographist

Nurses Technicians Cardiac surgeon

Cardiologist

Geriatrician

Valve + Platform durability is a crucial issue Little is known on valve durability and follow-up beyond 2 years â&#x20AC;˘ J. Webb: 70 patients (Circulation 2010) 1y 2y 3y Survival: 81% 74% 61%

Expanded Clinical indications to “Medium” or normal Risk AS ?

Lower EuroSCORE is associated with better results

1 yr Survival in the SOURCE Registry • Valve + platform durability should be > 10 yrs for Log standard risk> 40patients EuroSCORE 20-40 < 20 Survival

59.2%

73.5%

78.4%

Need for rigourous trial methodology with clear end-points definition, 100% in database, and randomized trials vs AVR in most-important subsets (standard risk patients)

Longest reported clinical follow-up (Rouen) Mrs S…, 90 y-old: > 6.5 years with THV

N

e f i l l orma

No valve dysfunction AVA: 1.68 cm², mean gradient: 12 mmHg

New Transcatheter Valves  Direct Flow  Sadra

?

GOALS

 Recoverable / repositionable  AorTx  Jena Valve  Lower  HLT

profile systems

 ABPS PercValve  No perivalvular  EndoTech  Ventor  More Embracer accurate  Symetis

leaks

positioning

 Percutaneous access and

TAVI for Bioprosthetic Valve Failure Endless Possibilities!

Trans-apical Approach Trans-apical MVR (valve-in-valve Webb JG, et al. Circulation 2010;121:151-6 + TAVI on AS) Aortic (n=10), mitral (n=7), pulmonary (n=6), and tricuspid (n=1) Edwards-Sapien Courtesy of Dr. John Webb

Conclusions After a 20 years odyssey, the dream has come true  The feasibility of TAVI has been fully demonstrated  TAVI is already increasingly accepted as a valuable alternative to AVR in high surgical risk AS patients

 Careful patients screening, excellent training and proctoring and an optimal partnership in the field of a Heart Team are the key of success

 The devices and procedures are steadily improving and an extension of indications can be anticipated

Conclusions TAVI is here to stay • In 2011, with technological advancements the number of centers and procedures should continue to expand in high surgical risk patients 

In 2012, depending on the PARTNER-US pivotal trial driven FDA’s decision, TAVI might explode in USA and worldwide in this subset of high risk patients

• Within 5 years, expansion of indications to other subsets of patients such as less severely ill /younger patients can be expected. Less invasive procedures (stent like) might be used in > 70% of the cases

Conclusions TAVI is here to stay â&#x20AC;˘ Within 10 years, it is likely that most patients with degenerative aortic stenosis will be treated using less invasive techniques than open-chest AVR.

If you want a happy ending, that depends of course, on where you stop!

Orson Welles (1915-1985)