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)