Download - CoreValve ADVANCE Study
![Page 1: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/1.jpg)
Unmet needs in TAVI: My sweet dreams
Ariel Finkelstein M.D.Tel Aviv Medical CenterTel Aviv, Israel
![Page 2: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/2.jpg)
Case Presentation
• E.K. 85 y-old male
• HTN
• Hypercholesterolemia
• Obesity
• Rec. pulmonary edemas SOB –
NYHA class III
![Page 3: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/3.jpg)
Echocardiography
![Page 4: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/4.jpg)
Echocardiography
![Page 5: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/5.jpg)
Hemodynamics-before
![Page 6: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/6.jpg)
Current Generation Devices:
That’s what we have, that’s
what we have to win with…
![Page 7: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/7.jpg)
Well, the vast majority looks like that
![Page 8: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/8.jpg)
BUT SOME WILL NOT…
![Page 9: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/9.jpg)
Like this
![Page 10: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/10.jpg)
And this
![Page 11: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/11.jpg)
And this…
![Page 12: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/12.jpg)
• Vascular complications
•Calcium
•Positioning-three
dimention
TAVI Technologies- what is neededTAVI Technologies: My main problems
![Page 13: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/13.jpg)
I have a dream…
![Page 14: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/14.jpg)
•CalciumAnti calcium technology
My TAVI dream
•Better positioningOn line imaging
•Vascular complicationsLower profile
![Page 15: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/15.jpg)
What doesn’t go with force…
![Page 16: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/16.jpg)
This is not enough…
![Page 17: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/17.jpg)
This is a buddy pigtail
![Page 18: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/18.jpg)
This time we were not that lucky
![Page 19: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/19.jpg)
Long, long torturouse road
![Page 20: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/20.jpg)
![Page 21: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/21.jpg)
Don’t let it mislead you…
![Page 22: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/22.jpg)
Don’t you ever forget: there are some other
access site alternatives. Like this…
![Page 23: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/23.jpg)
And this…
![Page 24: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/24.jpg)
And this
![Page 25: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/25.jpg)
Houston, we have a problem
• Vascular complications is a major threat during or following the course of TAVI.
• The problem includes perforation of the iliac-femoral arteries, critical stenosis and occlusion of the arteries, bleading and pseudoaneurysm formation.
• TAVI related vascular complications rate are in the range of ~10%-15%.
• Major vasclar complicationsincreased mortality.
![Page 26: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/26.jpg)
Randomized controlled
trials
Where does the evidence come from?
Registries
Small observational studies & reports
![Page 27: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/27.jpg)
PARTNER US completed
Randomized trials
PARTNER US Cohort B
PARTNER US Cohort A
![Page 28: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/28.jpg)
REGISTRIESFRANCE registry
German TAVI registry
U.K. TAVI registry
SOURCE registry
CoreValve Italian registry
ADVANCE registry
PARTNER EU registry
![Page 29: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/29.jpg)
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High Risk AVR Candidate
3105 Total Patients Screened
PARTNER Study Design
High Risk TA
ASSESSMENT:
Transfemoral
Access
TAVI
Trans
femoral
Surgical
AVR
High Risk TF
Primary Endpoint: All Cause Mortality (1 yr)
(Non-inferiority)
TAVI
Trans
apical
Surgical
AVR
1:1 Randomization1:1 Randomization
VSVS
Standard
Therapy
(usually BAV)
ASSESSMENT:
Transfemoral
Access
Not In Study
TAVI
Trans
femoral
Primary Endpoint: All Cause Mortality over
length of trial (Superiority)
1:1 Randomization
VS
Total = 1058 patients
2 Parallel Trials:
Individually PoweredHigh Riskn= 700 Inoperable n=358
![Page 30: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/30.jpg)
Vascular complications in
PARTNER
Leon M et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. N Engl J Med 2010;363:1597-1607.
•Partner 1 trial
–TAVI v’s standard TX (including balloon valvuloplasty) in non-operable patients
–179 patients in TAVI group
–22 or 24 Fr sheath
– In one year
• Overall 32%
• Major 17%
![Page 31: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/31.jpg)
Vascular complications in PARTNER
• Solely percutaneous approach
–Single center
–149 with full percutaneous approach
– 18-24 Fr Sheath
Stortecky et al. Percutaneous Management of Vascular Complications in Patients Undergoing Transcatheter Aortic Valve Implantation. J Am Coll Cardiol int 2012;5
Occurrence of vascular complications according to vascular access sheath size (A)
and by vascular closure crossover technique (B).
![Page 32: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/32.jpg)
P (log rank) = 0.069
Major Vascular Complication (n=31)
No Major Vascular Complication (n=148)
Mo
rta
lity
(%
)
Months
Mortality vs. Major Vasc Complics TAVI patients
27.7%
47.2%
![Page 33: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/33.jpg)
![Page 34: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/34.jpg)
FRANCE registry – early results
![Page 35: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/35.jpg)
The German Registry
![Page 36: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/36.jpg)
German registry – early results
![Page 37: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/37.jpg)
The British (U.K.) Registry
![Page 38: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/38.jpg)
U.K TAVI registry 30-d, 1y & 2y results
![Page 39: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/39.jpg)
The Italian Registry
![Page 40: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/40.jpg)
CoreValve Italian registry [n=181]Procedural variables
![Page 41: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/41.jpg)
CoreValve ADVANCE Study• 1,015 patients enrolled
from March 2010 to
July 2011
– 5 year follow-up
• 44 centers - 12
countries in Western
Europe, Asia and
South America
• All centers had
conducted at least 40
TAVI procedures prior
to the study and had
Heart Team in place
![Page 42: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/42.jpg)
30-day Outcomes
![Page 43: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/43.jpg)
Vascular Complications
9.5%7.5%
16.9%
3.9%
6.7%
0%
5%
10%
15%
20%
25%
30%
18 Fr S&E1*
N = 125
French2†
N = 66
German3‡
N = 588
UK4§
N = 460
Italian5||
N = 772
Perc
en
t o
f P
ati
en
ts (
%)
![Page 44: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/44.jpg)
Vascular complications in TAVI
Généreux P et al. Clinical Outcomes After Transcatheter Aortic Valve Replacement Using Valve Academic Research Consortium Definitions A Weighted Meta-Analysis of 3,519 Patients From 16 Studies. J Am Coll Cardiol 2012;59:2317–26
• Meta-analysis:
–16 studies describing vascular complications in accordance to first VARC definitions
–3519 patients (64-504 patients per study)
–Different TAVI approaches including trans-apical and subclavian approaches
–Different vascular access and closure approaches
–Only 4 studies included solely trans-femoral (120-186 patients )
![Page 45: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/45.jpg)
The problem- the culprit
• Large catheters, potentially traumatic.
• Closure devices designed for smaller
ports.
• Very sick and “vulnerable” patients.
• “hostile” peripheral vessels (calcified,
tortuous and thin vessels).
![Page 46: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/46.jpg)
I have a dream…
![Page 47: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/47.jpg)
Edwards SAPIEN 3 Transcatheter Heart Valve
System
External sealing ring
Cobalt-chromium frame
20, 23, 26, 29 mm Valve Sizes
Treated bovine pericardial tissue leaflets
Not approved for sale
Valve TF TA/TAo
20-26mm 14Fr 18Fr
29mm 16Fr 21Fr
Bench top Testing * Proof of Concept * Feasibility * OUS Study * Randomized Trial
![Page 48: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/48.jpg)
Edwards eSheath Introducer
Sheath Mechanism
•14 Fr, 16 Fr, 17 Fr, & 18 Fr sheath sizes
![Page 49: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/49.jpg)
Medinol Valve
![Page 50: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/50.jpg)
Handle
Braided Non-Absorbable
My best friend in the TAVI miliieu……
![Page 51: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/51.jpg)
He is pretty ugly…
![Page 52: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/52.jpg)
He is quite complicated to use…
![Page 53: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/53.jpg)
Its learning curve is long…
![Page 54: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/54.jpg)
And… one need to be a scoute in
order to manipulate the ties…
![Page 55: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/55.jpg)
But it is my only friend….
![Page 56: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/56.jpg)
…It is still my only friend….
![Page 57: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/57.jpg)
The unmet needs
• Smaller, less traumatic vascular entry ports.
• Lower profile, more flexible delivery systems.
• Designated “big holes” closure devices:
• surute based
• sealant (external plugs, hemostatic pads)
• combinations of the above
![Page 58: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/58.jpg)
My TAVI dream
•Anti calcium technology
•Better on line imaging
•Lower profile
![Page 59: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/59.jpg)
Yes, there is a problem. We call it
Calcium…
![Page 60: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/60.jpg)
And if it looks like
a Ca, it is a Ca...
![Page 61: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/61.jpg)
You got to be lucky sometimes
![Page 62: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/62.jpg)
Lucky again
![Page 63: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/63.jpg)
Holly shoot…
![Page 64: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/64.jpg)
I am tired of being lucky…
![Page 65: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/65.jpg)
And what about the PVL?
![Page 66: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/66.jpg)
This is the Achilles Heel of TAVI
Geometry and Apposition of based on MSCT
Schultz C et al. JACC 2009; 54:911-8
Delgado et al. Euro Heart J 2010;31:1114-1123
86% circular (eccentricity index <0.1)
50% circular (D1/D2 <0.1)
![Page 67: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/67.jpg)
Virmani et al. TAVI: Tips and tricks on how to avoid failure. Serruys PW et al. Informhealthcare 2010
12 months f/u
Will the biological response to the
CoreValve bioprosthesis mitigate
paravalvular aortic regurgitation over time?
Sealing effect?
![Page 68: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/68.jpg)
U.K TAVI registry 30-d, 1y & 2y results
![Page 69: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/69.jpg)
CoreValve ADVANCE Study
![Page 70: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/70.jpg)
German registry – early results
![Page 71: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/71.jpg)
AR following TAVI-German TAVI registry
Abdel-Wahab et al. Aortic regurgitation after transcatheter aortic valve implantation: incidence and early outcome. Results from the German transcatheter aortic valve interventions registry. Heart 2011;97:899e906
![Page 72: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/72.jpg)
I have a dream…
![Page 73: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/73.jpg)
Stone baster…
![Page 74: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/74.jpg)
Slide 74
ReLeaf’s Therapy – Valve Restoration
Technology
Laser Induced Shockwaves
Intense light pulse is converted into pressure wave that pulverizes hard tissue
Laser Induced Shockwaves
![Page 75: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/75.jpg)
Slide 75
Treated human calcific AV
76% increased orifice, 30 min lasing
Releaf Medical- decalcification technology
Laser Induced Shockwaves
![Page 76: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/76.jpg)
paravalvular leak sites paravalvular leak sites sealed
current gen tissue skirts next gen “expandable” skirts
endoluminal sciences expandable
skirt technology
Curtesy to Raj Makkar
![Page 77: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/77.jpg)
Endoluminal expandable skirt technology
![Page 78: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/78.jpg)
Edwards SAPIEN 3 Transcatheter Heart Valve
System
External sealing ring
Cobalt-chromium frame
20, 23, 26, 29 mm Valve Sizes
Treated bovine pericardial tissue leaflets
Valve TF TA/TAo
20-26mm 14Fr 18Fr
29mm 16Fr 21Fr
Bench top Testing * Proof of Concept * Feasibility * OUS Study * Randomized Trial
![Page 79: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/79.jpg)
Edwards CENTERA Self-Expanding
Transcatheter Heart Valve System
23, 26, 29 mm valve sizes Discrete valve design
Self-expanding nitinolframe
Treated bovine pericardial tissue leaflets
• Motorized delivery • 14 Fr system
Bench top Testing * Proof of Concept * Feasibility * OUS Study * Randomized Trial
Not approved for sale
![Page 80: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/80.jpg)
My TAVI dream
•Anti Calcium technology
•Better on line imaging
•Lower profile
![Page 81: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/81.jpg)
How exactly am I suppose to
deploy it?
![Page 82: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/82.jpg)
How exactly am I suppose to
deploy it?
![Page 83: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/83.jpg)
Paeion- Optimal Projection
Marking 1st projection Marking 2nd projection
![Page 84: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/84.jpg)
C-THV Position Planning – Sapien XT
Hinges line
Aortic delineation
![Page 85: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/85.jpg)
C-THV Real-Time Positioning Sapien XT
Real-Time Positioning Deployment Post-Deployment Injection
![Page 86: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/86.jpg)
I love to have this
![Page 87: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/87.jpg)
And this
![Page 88: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/88.jpg)
And mainly this…
![Page 89: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/89.jpg)
RealView Imaging - Medical
Holography in the Cath Lab
![Page 90: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/90.jpg)
RealView Imaging’s
Holographic Technology“In-Air” Holographic Display and Interface System for Medical Imaging Applications
Key differentiators:
• True visualization: true volume in true space
• Direct and precise interaction within the image
![Page 91: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/91.jpg)
RealView Imaging - Holographic
Concept for the Cath Lab
![Page 92: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/92.jpg)
• Lower profile devices ~ 16-14 Fr or smaller
• Dedicated delivery systems
• Better big holes closure devices
• Anti Ca technology
• Improved circumferential annulus fixation
To reduced para-valvular AR
• Optimal positioning before/during deployment
(improved placement position)
Advanced imaging
Localization and stabilizing features
Retrievable and repositionable
TAVI Technologies-what is needed
![Page 93: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/93.jpg)
Valve Prosthesis
![Page 94: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/94.jpg)
PARTNER Final ThoughtsRarely, in Medical Research,
has so dramatic an improvement in Survival,
been achieved in such a Short Time,
with so few Iterations;
And it is only the Beginning of a Flooding
Tide,
that Floats All Boats!!!
Martin B. Leon
![Page 95: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/95.jpg)
Those are my TAVI dreams…
![Page 96: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/96.jpg)
My TAVI dream…
Now, let’s talk
about my true
small tiny TAVI
dream…
![Page 97: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/97.jpg)
![Page 98: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/98.jpg)
![Page 99: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/99.jpg)
•
![Page 100: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/100.jpg)
![Page 101: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/101.jpg)
THANK YOU FOR YOUR ATTENTION
![Page 102: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/102.jpg)
Transcatheter Aortic Valve Implantation
in High Risk Patients with Severe
Aortic Stenosis:
TASMC Experience - First 300 Patients
Finkelstein et al, submitted
![Page 103: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/103.jpg)
PAVI - TASMC
• 300 patients between March 2009 to Sept. 2012
• Age: 83.3 ± 5.4, range 63-98
• 115 Males (38%), 185 Female (62%)
• Logistic EuroScore (%): 26 ± 13.1
• Approach: 293 - Transfemoral, 7 – subclavian
• 250 – CoreValve, 50 - Edwards
Finkelstein et al, submitted
![Page 104: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/104.jpg)
Co-Morbidities %
of
pati
en
ts
Finkelstein et al, submitted
![Page 105: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/105.jpg)
Co-Morbidities
• OP=Osteoporosis;
PHTN=Pulmonary Hypertension;
PPM=Permanent Pacemaker
0%
20%
40%
60%
80%
100%
PVD CHF CVA CAF OP PHTN PPM
10%
39%
9%17%
29%
62%
7%
% o
f p
ati
en
ts
![Page 106: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/106.jpg)
Peak & Mean Echo Pressure Gradients
Finkelstein et al, submitted
![Page 107: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/107.jpg)
% o
f patients
Finkelstein et al, submitted
![Page 108: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/108.jpg)
NYHA Class
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
30 Days 6 Months 1 Year
88% 85% 83%
8% 10% 13%
2% 5% 4%3% 0% 0%
I II III IV
% o
f p
ati
en
ts
![Page 109: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/109.jpg)
Complications (30 Days)
1% cardiogenic shock; 2% sepsis, 2% mod.-sev. AR
% o
f p
ati
en
ts
![Page 110: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/110.jpg)
30 Days Mortality%
of
pati
en
ts
![Page 111: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/111.jpg)
Mortality%
of
pati
en
ts
![Page 112: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/112.jpg)
Vascular complications in TAVI
• No relation to mortality observed between with and without VC
–30 days 1/39 [2.5%] vs 6/254 [2.4%]; p=0.939
–6 months non significant trend. 4/31 [12.9%] vs 14/208 [6.7%]; p=0.224
2.40%
6.70%
2.50%
12.90%
%00.0
%00.2
%00.4
%00.6
%00.8
%00.01
%00.21
%00.41
30 days 6 months
VC+VC- VC+VC-
![Page 113: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/113.jpg)
Acute Kidney Injury following TAVI
Stage 3(0/251)
Stage 2(4/251)
Stage 1(38/251)
Total(42/251)
0%
1,60%
15,10%
16,70%
![Page 114: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/114.jpg)
Acute Kidney Injury following TAVI
Edwards vs. CoreValve:
Edwards(9/38)
Corevalve(33/213)
Total(42/251)
23,70%
15,50%
16,70%
AKI
P=0.238
Edwards(9/38)
Corevalve(33/213)
162
142
Contrast media (ml)
* p=0.02
![Page 115: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/115.jpg)
Hemodynamic effect of TAVI
(entire cohort)
91
36
62
34
6969
91
42
56
39
6269
EDV mlESV mlLVEF (%)SPAP mmHgRV stroke vol (ml)
HR (bpm)
Follow up
Baseline
*
**
*
* P<0.001
HR-heart rate, RV –right ventricle, SPAP-systolic pulmonary artery pressure, ESV-
end systolic volume.
![Page 116: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/116.jpg)
Baseline hemodynamic profile of TAVI patients with
normal (EF≥60%, n=56), near normal (EF=50-60%, n=66), and
abnormal (EF<50%, n=44) LV systolic function
LVEF<50
LVEF=5…
LVEF>60
0
20
40
60
80
100
120
140
160
180
200
EDV mlESV ml
LVEF (%)SPAP mmHg
RV stroke vol (ml)HR (bpm)
LVEF<50
LVEF=50-60
LVEF>60
![Page 117: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/117.jpg)
Hemodynamic effect of TAVI in subgroups of abnormal,
near normal and normal LV systolic function
-21
29
-41
18
-10
13
-19
7
-9
4,7
-14
8
ESV ml LVEF (%) SPAP mmHg Stroke vol
% Change LVEF<50 % Change LVEF=50-60 % Change LVEF>60
![Page 118: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/118.jpg)
Slide 118
ReLeaf’s Therapy – HighlightsSafe
– No implant
– Safe femoral access (low profile catheter)
– Preserves native valve tissue
– Short hospital stay
Simple
– 45 min. intuitive procedure
– Of the shelf complementary devices, standard imaging
Cost - effective
– Significant relief in symptoms
– 2-3 years effect
– Low Cost
![Page 119: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/119.jpg)
Slide 119
In-Vivo Study
– Animal model• Porcine native aortic valve
– Procedures• Open heart surgery (n=2), Catheterization (n=4)
• Navigation, energy delivery, emboli capture
• 1-2 month FU (echo), histology
– Results• Short and simple minimally invasive procedure
• Easy navigation & energy delivery to the AV
• No aortic regurgitation, no tissue scarring
• Further testing with improved emboli release method needed
Intracardiac Echo
Fluoroscopy
Catheter
ICE
Filters after trial
![Page 120: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/120.jpg)
Releaf Medical- decalcification technology
![Page 121: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/121.jpg)
![Page 122: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/122.jpg)
You start with
that…
![Page 123: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/123.jpg)
Vascular complications in TAVI
Smith C et al. Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients. N Engl J Med 2011;364:2187-98.
•Partner 2 trial:
–TAVI v’s AVR high-risk patients candidates for surgery
–348 patients in TAVI group
–22 or 24 Fr sheath
–In one year
• Overall 18%
• Major 11%
![Page 124: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/124.jpg)
P (log rank) = 0.0046Major Bleed (n=46)
No Major Bleed (n=133)
Mo
rta
lity
(%
)
Months
Mortality vs. Major Bleeding TAVI patients
26.3%
43.5%
![Page 125: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/125.jpg)
Sometimes we just go one step
further…
![Page 126: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/126.jpg)
AR following TAVI
• Edwards Sapien prosthesis
– 84 patients with serial echocardiography
– 75% had AR following implant
– Mostly paravalvular
– At one year:
• The mean AR grade increased (not significantly)
• Not resulting in LV function impairment
Yared k et al. Impact of Aortic Regurgitation After Transcatheter Aortic Valve Implantation: Results From the REVIVAL Trial . J Am Coll Cardiol Img. 2012;5(5):469-477
![Page 127: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/127.jpg)
AR following TAVI
• AR index
– 146 patients, 71 mild AR, 22 mod to sev AR
– AR index independently predicted 1-year
mortality hazard ratio: 2.9, 95% confidence interval: 1.3
to 6.4; p = 0.009.
Sinning et al. Aortic Regurgitation Index Defines Severity of Peri-Prosthetic Regurgitation and Predicts Outcome in Patients After Transcatheter Aortic Valve Implantation . J Am Coll Cardiol Img. 2012;59(13):1134-1141
![Page 128: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/128.jpg)
Slide 128
Calcific Aortic Stenosis
Normal Stenotic
Disease Progression
• Patients with mild to moderate aortic stenosis
• Mostly Asymptomatic
• No therapy required
Calcium accumulation
![Page 129: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/129.jpg)
Sometimes you are
not that lucky…
![Page 130: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/130.jpg)
C-THV Optimal Projection
![Page 131: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/131.jpg)
PARTNER US cohort B
23mm and 26mmvalve sizes
22F and 24Fsheath sizes
Retroflex 1Edwards-SAPIEN THV
![Page 132: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/132.jpg)
Patient Characteristics -
1CharacteristicTAVIn=179
Standard Rxn=179
P value
Age - yr 83.1 ± 8.6 83.2 ± 8.3 0.95
Male sex (%) 45.8 46.9 0.92
STS Score 11.2 ± 5.8 12.1 ± 6.1 0.14
Logistic EuroSCORE 26.4 ± 17.2 30.4 ± 19.1 0.04
NYHA
I or II (%)
III or IV (%)
7.8
92.2
6.1
93.9
0.68
0.68
CAD (%) 67.6 74.3 0.20
Prior MI (%) 18.6 26.4 0.10
Prior CABG (%) 37.4 45.6 0.17
Prior PCI (%) 30.5 24.8 0.31
Prior BAV (%) 16.2 24.4 0.09
CVD (%) 27.4 27.5 1.00
![Page 133: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/133.jpg)
Standard Rx
TAVI
All
-cau
se m
ort
ali
ty (
%)
Months
∆ at 1 yr = 20.0%
NNT = 5.0 pts
50.7%
30.7%
1ry Endpt - All Cause Mortality
![Page 134: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/134.jpg)
0 6 12 18 24
Cardiovascular Mortality
Standard Rx
TAVI
Card
iovascu
alr
mo
rtali
ty (
%)
Months
0
20
40
60
80
100
∆ at 1 yr = 24.1%
NNT = 4.1 pts
44.6%
20.5%
![Page 135: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/135.jpg)
5 Medical Therapies Proven to Reduce Death
Therapy Indication # pts Relative Absolute
Aspirin MI 18,773 23% 2.4%
Fibrinolytics MI 58,000 18% 1.8%
Beta blocker MI 28,970 13% 1.3%
ACE inhibitor MI101,00
06.5% 0.6%
Aspirin 2nd prev 54,360 15% 1.2%
Beta blocker 2nd prev 20,312 21% 2.1%
Statins 2nd prev 17,617 23% 2.7%
ACE inhibitor 2nd prev 9,297 17% 1.9%
Adapted from Granger CB and McMurray JJV JACC 2006; 48:434
Reduction in deaths
![Page 136: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/136.jpg)
0 6 12 18 24
Standard Rx
TAVI
All
-cau
se m
ort
ali
ty o
r
Rep
eat
Ho
sp
italizati
on
(%
)
Months
0
20
40
60
80
100∆ at 1 yr = 29.1%
NNT = 3.4 pts
71.6%
42.5%
Repeat Hospitalizaion
![Page 137: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/137.jpg)
Walking Distance
P = 0.002
Walk
ing d
ista
nce (
mete
rs)
Baseline 30 Days
Six-Minute Walk Tests
P = 0.004
1 Year
P = 0.67
P = 0.55
![Page 138: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/138.jpg)
NYHA Class Over Time
P = 0.68 P < 0.0001 P < 0.0001 P < 0.0001
I II III IV
TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx
Perc
en
t
TreatmentVisit
Baseline 30 Day 6 Month 1 Year
![Page 139: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/139.jpg)
Baseline 30 Day 6 Months 1 Year
Mean
Gra
die
nt
(mm
Hg
)
50
40
30
20
60
70
10
0
Error bars = ± 1 Std Dev
Mean Gradients Over Time
P < 0.0001
33.0
39.5
44.4
43.2 12.111.310.8
44.6
Standard Rx
TAVI
![Page 140: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/140.jpg)
AV
A (
cm
2) 1.5
1.0
0.5
0
2.0
2.5
Baseline 30 Day 6 Months 1 Year
Error bars = ± 1 Std Dev
Aortic Valve Areas Over Time
P < 0.0001
1.53
1.61
1.57
0.64
0.700.680.77
0.65
Standard Rx
TAVI
![Page 141: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/141.jpg)
Paravalvular Regurgitation: TAVI
No changes over time
None/Trace
Mild
Moderate
Severe
30 Day 6 Month 1 Year
![Page 142: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/142.jpg)
Pe
rce
nt
* Constant Hazard Model
3% *
28%30%
12%
5%
23%
0
10
20
30
40
50
60
70
80
90
100
Breast Lung Colorectal Prostate Ovarian Severe
Inoperable AS
5 Year Survival: Metastatic Cancer
Mortality in Standard RxPerspectives
Courtesy of Murat Tuzcu, Interventional PI, CCF
![Page 143: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/143.jpg)
PARTNER US cohort A
![Page 144: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/144.jpg)
![Page 145: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/145.jpg)
CoreValve Italian registry 30-d outcomes
![Page 146: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/146.jpg)
Procedural Results
![Page 147: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/147.jpg)
| Valve Performance
![Page 148: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/148.jpg)
Disclosure Statement of
Financial Interest
Within the past 12 months, I or my spouse/partner have had a
financial interest/arrangement or affiliation with the
organization(s) listed below.
Company Financial Relationship
Edwards Lifesciences consultant and proctor
Medtronic consultant and proctor
![Page 149: CoreValve ADVANCE Study](https://reader031.vdocuments.us/reader031/viewer/2022012923/586f68901a28ab35738be87f/html5/thumbnails/149.jpg)