CoreValve®
Durability and Valve Performance
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Caution: For distribution only in markets where CoreValve has been approved.
Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
Not approved in the USA, Canada or Japan.
UC201202505c EE
Medtronic Bioprosthesis Evolution
Third Generation
Product Features
Hancock I
1970’s
Second Generation
First Generation
• High Pressure
Fixation
• Large native
muscle bar
• Flexible Stent Posts
Rigid Inflow
• Low/ Zero pressure
• Toluidine Blue, T6
• Flexible stent
*CoreValve
• Supra-Annular
• Porcine
Pericardium
Freestyle
• Physiologic Fixation
• AOA
• Flexible Stent
Melody
Hancock II
1990’s
Mosaic
• Pulmonic
Transcatheter
• Bovine Jugular
Vein
1980’s
Hancock MO
Intact
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Not approved in the USA, Canada or Japan.
12
Hancock II
David and colleagues
94%
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Not approved in the USA, Canada or Japan.
89.8%
Mosaic
®
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Not approved in the USA, Canada or Japan.
Transcatheter Aortic Valves
The Durability Challenge
How do we go from here………..
to here
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Not approved in the USA, Canada or Japan.
and never end up here
Valve Durability: A Lesson from Surgical Valves
Maintaining Proper Leaflet Motion is Critical to Long Term Valve Durability
• Leaflet bending/folding during valve operation induces high stresses on
leaflets. High bending stresses on leaflets can lead to bending fatigue
and potentially delamination, calcification, and/or valve failure 1
• Misalignment, leaflet prolapse, asynchrony, poor coaptation, high
commissure stress, pinwheeling/bending may lead to early failure.
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Not approved in the USA, Canada or Japan.
1. Schoen 1987
Surgical Pericardial Valve Failures
Current generation surgical
pericardial bioprostheses
reveal that these devices can
exhibit SVD leading to explant
as early as two to four years
with continued risk of failure
over time
1 Cosgrove D, Lytle B, Taylor P, et al. The Carpentier-Edwards Pericardial Aortic Valve Ten-Year Results. J Thorac Cardiovasc Surg. 1995;110:651-62.
2 Roselli E, Smedira N, Blackstone E. Failure Modes of the Carpentier-Edwards Pericardial Bioprosthesis in the Aortic Position J Heart Valve Dis 2006;15:421-8.
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
CoreValve Design + Tissue Selection =
Durability and Performance
Supra-annular valve design
provides optimal leaflet
coaptation
Commissure height and
deep leaflet cuts minimize
leaflet stress
Self-expanding nitinol
frame enhances durability
and deliverability
Porcine pericardium is
the optimal tissue for
valve performance and
low-profile delivery
AOA® anti-mineralization treatment reduces
both early and late valvular calcification*
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
*AOA anti-mineralization treatment will be available on
CoreValve in Fall 2012.
Frame Design Challenges
Design Requirement
Challenges to Durability
Self-anchoring/Migration
• Material capable of providing appropriate
radial force over a range of sizes and shapes
Delivery Profile
• Frame capable of withstanding crimp profile
Span a range of sizes with a
single valve and accommodate
anatomical variations
• Frame capable of maintaining structural
integrity spanning a range of sizes and
shapes
Withstand in-vivo loading
• Frame capable of withstanding multiple
modal cycle loading (radial, compression,
torsion, etc.)
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
Frame Fatigue Analysis & Testing
• Rigorous analysis of CoreValve patient CT datasets provided definition
of aggressive boundary condition input for FEA and fatigue tests
• State of the art finite element (FEA) methods used to predict strain
distribution within frame under combined loading modes
• Frame fatigue testing successfully completed to 600M cycles (15yrs)
under multiple test conditions to demonstrate frame durability
Enhanced In Vivo
Deformation Analysis
from CT Data
Combined Loading
FEA
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Not approved in the USA, Canada or Japan.
600M Cycle Frame
Fatigue Testing
Bench test results shown on this slide and throughout the
presentation may not be indicative of clinical performance.
Migration Conduit Development & Testing
• Patient CT scans are studied to determine the most challenging
anatomical conditions for the CoreValve frame
• Test conduits are developed from materials designed to match the
compliance of the human aorta
• Valves are tested for migration resistance up to stage 3 hypertensive
flow conditions
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
Tissue Design Challenges
Design Requirement
Challenges to Durability
Delivery Profile
• Prevent tissue damage during crimping,
tracking, and deployment
Span a range of sizes with a
single valve
• Preserve long term leaflet function/motion
Accommodate anatomical
variations
• Mitigate distortion at the valve level to maintain
coaptation alignment and leaflet motion
• Minimize redundancy that leads to extreme
leaflet bending
Withstand potential postimplant BAV
• Post-implant BAV must not damage tissue
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
Porcine pericardium is the optimal tissue for valve
performance and low-profile delivery
• The ultimate tensile strength (UTS) and
suture pull out stresses for porcine and
bovine pericardium are statistically
equivalent1,2
9
8
7
• Peak physiologic stresses are significantly
less than both UTS values3
6
MPa
• Porcine pericardium thickness is about
half that of bovine. Thinner tissue
prevents tissue damage during crimping,
tracking, and deployment, allowing for
low-profile delivery across all valve
sizes.1,4
5
4
3
2
Peak Physiologic Stress
1
1.
2.
3.
4.
Sacks MS. Uniaxial mechanical and structural properties of bovine versus porcine pericardial tissue. Medtronic
Engineered Tissue Mechanics Laboratory. University of Pittsburgh, Pittsburgh, PA. January 17, 2008. Data on File.
Garcia Paez JM, Carrera A, Herrero EJ, et al. Influence of the selection of the suture material on the mechanical
behavior of a biomaterial to be employed in the construction of implants.
Part 2: porcine pericardium. J Biomater Appl. 2001;16:68-90.
Li, K and Sun, W. “Simulated thin pericardial bioprosthetic valve leaflet deformation under static pressure-only loading
conditions: Implications for percutaneous valves” Ann Biomed Eng. 2010 Aug;38(8):2690-701.
Braga-Vilela AS, Pimentel ER, Marangoni S, Toyama MH, de Campos Vidal B. Extracellular matrix of porcine
pericardium: Biochemistry and collagen architecture. J Membr Biol. 2008 Jan;221(1):15-25.
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
0
Porcine
Bovine
AOA® anti-mineralization treatment reduces both
early and late valvular calcification
•
•
•
Alpha-amino oleic acid (AOA) treatment inhibits calcium formation on
prosthetic valve leaflets.
Unlike surfactants, AOA convalently bonds with the tissue to block calcium
binding.
AOA has 20 years of proven clinical success on Medtronic’s surgical valves.1
Non-treated Tissue
Glutaraldehyde preserved
tissue
AOA® Treated Tissue
The likelihood of calcification
increases on nontreated tissues
Tissue Glutaraldehyde
Matrix
AOA covalently bonds to the free aldehyde
groups in the glutaraldehyde tissue
AOA
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Not approved in the USA, Canada or Japan.
Blood Cell
AOA reduces both early and late
valvular calcification
Calcium
1. Medtronic Freestyle Aortic Root Bioporsthesis was first implanted clinically in August 1992.
*AOA anti-mineralization treatment will be available on
CoreValve in Fall 2012.
Valve Height Reduces Leaflet Stresses
• Areas of high stress can induce collagen degeneration that over time
could lead to tearing and valve failure1
• Valve designs that reduce leaflet stresses “are likely to have improved
performance in long-term applications”2
17 mm tall
14 mm tall
12% Lower Stress in the Taller Valve
1. Schoen Frederick J. Cardiac Valve Prostheses: Pathological and Bioengineering Considerations. J Cardiac Surg.
1987;2:65-108.
2. Sun W., Li K., Sirois E. Simulated elliptical bioprosthetic valve deformation: Implications for
asymmetric transcatheter valve deployment. J Biomech. 2010;43:3085-3090.
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
Finite Element Analysis (FEA) Demonstrates
Reduction in Leaflet Stresses Over Traditional
Valve Designs1
120 mm Hg of Pressure is Applied to Both Valves
Max Stress = 1.34 MPa
1. Data on file at Medtronic
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Not approved in the USA, Canada or Japan.
Max Stress = 1.50 MPa
Supra-Annular Valve Design Can Mitigate Impact
of Elliptical or Undersized Deployment
• Flexible frame conforms to native annulus shape while maintaining
bioprosthesis in a higher position
• Decoupling of valve from native annulus minimizes ellipticity at the
valve level 1
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
1. Data on file at Medtronic
Crimping For Up To 60 Minutes Does Not Damage
the CoreValve Tissue
• CoreValve bioprostheses (n=8) were crimped and loaded according to the IFU for
15, 30, 45 and 60 minutes
• TCV leaflets were inspected under microscope, then removed from the frame and
sectioned for histologic analysis
• Microscopic inspection showed faint imprints that rehydrated quickly during the
course of inspection. No evidence of damage was seen on the sutures, leaflets, or
skirt tissues
• Histologic inspection showed mild indents, but these were not correlated to
impression sites and were also found on control leaflets
These indents do not correspond to a site of observed imprints
cut MOA
H1
FM
H2
section
sectionF1
F1
These indents are in the area of the observed imprints
cut MOA
FM
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Not approved in the USA, Canada or Japan.
section
sectionF2
F2
Medtronic has Performed Rigorous Testing to
Confirm the Safety of Post-Implant BAV
• In two separate studies, CoreValve bioprostheses were deployed in synthetic and
tissue conduits that were modeled after calcified human aortic anatomy
• Balloon dilatation was performed using 25mm and 28mm NuMed, Z-Med II
balloons at maximum-rated burst pressures for 5 seconds
• Valves were inspected immediately after removal of the balloon, then assessed
for hydrodynamic performance on a pulse duplicator
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Not approved in the USA, Canada or Japan.
Post-Implant Balloon Dilatation Does Not Damage
CoreValve’s Tissue, Frame, or Sutures
Conclusions
• Inspections showed no evidence of damage to either the valve tissues
or assembly sutures in either study
• The hydrodynamic performance data showed that there was no
significant difference in EOA between pre and post balloon dilatation
Pre Balloon Dilatation
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Post Balloon Dilatation
Performance
• Accelerated wear testing (AWT) was performed on 24 valves
in both circular and elliptical configurations
– Valves were cycled for 200 million cycles (5 years)
– Result: Minimal valve wear and low stable gradient and
regurgitation levels
Circular Deployment
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Elliptical Deployment
1.35 aspect ratio
Tissue Integrity
• Histology performed on leaflet samples after 200 million cycles in an
elliptical configuration
– All test samples were crimped and loaded into the delivery
system prior to wear testing
– Leaflets showed no evidence of internal leaflet delamination or
collagen loss
– Laser-cut free margins were fully intact1
outflow
inflow
Figure 1. Leaflet as received
1. Data on file at Medtronic
Figure 2. Slices submitted
for histopathology
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Not approved in the USA, Canada or Japan.
Figure 3. The pericardial leaflet
section is intact
Conclusions
• There have been over 27,000 CoreValve device implants in over 50
countries since the first implantation in 2004
• No frame fractures have been reported in an implanted CoreValve
device to date
• In AWT, CoreValve device demonstrated a consistently low regurgitant
fraction and stable EOA from base line to post-200 million cycles
• Long-term (3 and 4-year) durability is indicated by the absence of
structural valve deteriorations and sustained hemodynamic
performance
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.
CoreValve is a registered trademark of Medtronic CV Luxembourg S.a.r.l.
AOA is a registered trademark of Medtronic, Inc.
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Caution: For distribution only in markets where CoreValve has been approved.
Not approved in the USA, Canada or Japan.