In Perspective: Impact of new TAVI Devices on TAVI...
Transcript of In Perspective: Impact of new TAVI Devices on TAVI...
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!