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Presenter/Author: Matthew Krever1, Principal Engineer
Co‐Authors: Adam Groothuis2, PhD, George Hanzel3, MD, Ted Bachman1, Erin Black1, Rudy Cedro1, Dan Olsen1, Natalie Macon4, PhD.1: Cordis Corporation, 2: Concord Biomedical Sciences & Emerging Technologies, 3: Beaumont Heart Center, 4: Secant Therapeutics
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1. Targeted Disease State & Opportunity
2. Ideal Device Profile (IDP) Development
3. Direct Plication Annuloplasty (DPA)
4. DPA comparison to the IDP
Overview
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1. LV enlarges (ischemia)
2. Mitral annulus dilates
Targeted Problem: Functional Mitral Regurgitation
4. One‐way valve becomes leaky, or "regurgitant”
5. LV pumps more blood to maintain normal output
3. Valve leaflets pull apart
MR adds to downward cycle of CHF, demanding more than heart can provide.
Leakymitralvalve
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The OpportunityUnmet need• Significant CHF / FMR population1,2,3
• ~ 30% of CHF / FMR is moderate to severe3
• Almost 1 in 3 people > 55 years will develop CHF4
• Post‐op MR recurrence rate up to 30% at 6 months5
CHF1, 2 FMREstimate
Mod‐Severe FMR Estimate
WW Prevalence
23,000,000 12,880,000 3,864,000
WW Incidence
2,000,000 1,120,000 336,000
US Prevalence
5,800,000 3,248,000 974,400
US Incidence 550,000 308,000 92,400
In US, only ~20,000 MV surgical procedures
done in 2009 6(includes non‐FMR cases)
U.S. direct and indirect cost of CHF in 2010: $39.2 billion1
1Trichon et al, Am J Cardiol 2003;91:538‐5432Birnbaum et al. Coron Artery Dis 2002;13:337‐3443Agricola et al Eur J Heart Failure 2009;11:581‐5874Bonow et al ACC/AHA VHD Guidelines, Circulation 20085Bauma et al Eur J Cardiothoracic Surg 2010;37:170‐1856Vahanian et al ESC HVD Guidelines, Eur Heart J 2007
FMR56%
No FMR44%
Congestive Heart Failure (CHF)
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•Consider Needs of the “Four P’s”•Patient: the person for whom the device is used•Provider: typically the physician “end‐user”•Payer: typically the insurer and/or hospital paying for and obtaining the device
•Producer: the device manufacturer and seller
•Can be determined through “Voice of Customer” techniques such as Jobs‐Outcomes‐Constraints1
Developing an Ideal Device‐Based Solution Profile
1. Ulrich, Anthony W., What Customers Want: Using Outcome Driven Innovation to Create Breakthrough Products and Services, McGraw‐Hill: 2005.
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An “Ideal” Device‐Based Solution for FMR‐ Ideal Device Profile ‐
Producer
PayerPatient
Provider
MAJOR REQUIREMENT TYPES
Technical
CommercialClinical
Procedural
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•Procedural• How to deliver therapy
• ↓ invasiveness• ↓ navigation & guidance complexity • ↓ number of procedural steps & time required
• ↓ number of physician specialties required
• ↓ number of devices required• ↓ learning curve for providers• Does not require cardiac bypass
• How to achieve therapeutic effect•Technical •Clinical•Commercial
Ideal Device Profile
• ↑ ability to deliver• ↑ ability to precisely control
placement• ↑ safety of approach
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•Procedural•How to deliver therapy•How to achieve therapeutic effect
• Ability to “preview” effect prior to commitment• Repositionable• Intraprocedural customization: site & magnitude of effect • ↓ “footprint” of device
•Technical •Clinical•Commercial
Ideal Device Profile
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•Procedural•Technical•↓ device complexity•↓ device manufacturing cost•↓ device size/profile • Optimize implant chronic durability•↑ implant biocompatibility (flow impact, tissue response, thrombosis)
•↑ delivery system reliability
•Clinical•Commercial
Ideal Device Profile
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•Procedural•Technical •Clinical•↑ Efficacy•↑ Safety•↑ Durability of effect•↓ Economic burden to society•↓ Impact to future treatment options
•Commercial
Ideal Device Profile
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•Procedural•Technical •Clinical•Commercial•↑ Intellectual property protection & FTO•↑ Target market size•↑ Target market growth rate•↑ Gross profit•↓ Market risk•↓ Reimbursement risk
Ideal Device Profile
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An Overview
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Direct Plication Annuloplasty (DPA)The Approach: acting directly on the MV annulus,
reshape the valve to improve function
Device Effect: reduce mitral valve circumference
Objectives:• Reduce mitral valve annular diameter• Improve leaflet coaptation• Reduce mitral regurgitation
1. Plicate (releasable)
2. Deliver Clip
3. Relocate and repeat if needed
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Direct Plication Annuloplasty Procedure
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DPA System Components
Deflecting Guide (DG)
Distal Deflection ControlProximal Deflection Control
Device Introduction Valve
Flush Lumen
Crossing Catheter
Tissue Retainer Clips
9mmDelivered
UndeliveredJaws Closed
JawsOpen
Plicator
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Illustrative Examples
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Typical Testing Regimen1. Functional Testing in Tortuous Path & Glass
Models• Deliverability and Pushability• Jaw Rotation and Function (open/close)• Clip Fire
2. Plicator Min Bend Radius3. Plicator Jaws
• Jaw Force• Jaw Span• Jaw Bias
4. Clip Pull Out Force5. Ex‐vivo Studies
• Dimensional• Shape change
6. In Vivo Studies (Porcine models)• Acute (how to deliver/achieve therapy)• Chronic (safety/durability of effect)
IterativeProcess
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2D Tortuous Path Model Based on Porcine LV
Rev.1: LV curve based on successful pre‐clinical
Test Parameters:• LV Curve: Centerline Radius• Width of Curve• Water Bath, 37°CTest Output:• Ability for plicator to navigate curvature and retain clip firing function
Rev.2: aortic arch and LV curve more representative of actual undistorted anatomy
Angiogram of system in place prior to delivering clip
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Getting the DG shape correct……iterate and test
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Plicator (cutaway view)
Jaws
slots
Clip
Pusher
Threaded rod
Dovetail cut outer shaft
Nut
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IMCA (1)
Single Clip Plicator
Single Clip Plicator (moved nut)
Stainless flat ribbon coil
Stainless flat ribbon coil (distal)
Dovetail laser cut pattern on nitinol
•Not torqueable – cannot orientate jaws in proper grabbing plane
•Coil is very stiff – extremely difficult to pass through deflected guide
•Highly torqueable
•Laser cut section very flexible
•Distal coil, clevis and jaw combination result in very stiff distal region that distorts deflecting guide when passed
Nut
Critical Evolution of Plicator
•Highly torqueable
•Laser cut section (distal & prox.) very flexible
•Distal stiff region length reduced to enable passing through guide with much less force & distortion
Dovetail laser cut pattern on stainless steel
Dovetail laser cut pattern on nitinol
Gray bars represent length of inflexible region
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Ex Vivo Plication (Proof of Concept)Before Plication
LA View
After Plication
Suture markers for dimensional reference only
Examples of Subvalvular Clip Placement and Plication
MV Annulus
LV View
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Direct Plication Annuloplasty ‐ Preclinical Proof of ConceptPlication and Clip Delivery to Annulus at P2
P2 Region
In Vivo Plication
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Understanding the next challenges
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3D Models Based on CT Patient Zero – Processed data files (unnecessary anatomy removed)
1. Processed CT cross‐section with relevant left side anatomy in pink
Papillary Muscles
Aortic Valve
2. Converted CT data into 3D CAD
format
3. Merged aortic arch from other CT
data set and removed artifact.
This computer model can be used
to create rapid prototypes and
molds for compliant 3D
bench models.
Patient Info: Normal Heart, @75% of the R‐R Interval
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Evolving the Proper FitPig Model vs. Human Model
Pig Model with Pig DG
Good Fit
Human Model with Human DG
Good FitPig DG Has Poor Fit
Human Model with Pig DG
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A Summary
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•Procedural• How to deliver therapy
• ↓ invasiveness• ↓ navigation & guidance complexity • ↓ number of procedural steps & time required
• ↓ number of physician specialties required
• ↓ number of devices required• ↓ learning curve for providers• Does not require cardiac bypass
• How to achieve therapeutic effect•Technical •Clinical•Commercial
DPA vs. Ideal Device Profile
• ↑ ability to deliver• ↑ ability to precisely control
placement• ↑ safety of approach
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•Procedural•How to deliver therapy•How to achieve therapeutic effect
• Ability to “preview” effect prior to commitment• Repositionable• Intraprocedural customization: site & magnitude of effect • ↓ “footprint” of device
•Technical •Clinical•Commercial
DPA vs. Ideal Device Profile
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•Procedural•Technical•↓ device complexity•↓ device manufacturing cost•↓ device size/profile •Optimize implant chronic durability•↑ implant biocompatibility (flow impact, tissue response, thrombosis)
•↑ delivery system reliability
•Clinical•Commercial
DPA vs. Ideal Device Profile
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•Procedural•Technical •Clinical•↑ Efficacy•↑ Safety•↑ Durability of effect•↓ Economic burden to society•↓ Impact to future treatment options
•Commercial
DPA vs. Ideal Device Profile
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•Procedural•Technical •Clinical•Commercial•↑ Intellectual property protection & FTO•↑ Target market size•↑ Target market growth rate•↑ Gross profit•↓ Market risk•↓ Reimbursement risk
DPA vs. Ideal Device Profile
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Conclusions• It is valuable to establish an Ideal Device Profile (IDP) which enables well‐targeted product development.• An IDPmaximizes holistic product development and reduces risk of inadequate solutions.
• Direct Plication Annuloplasty is a novel approach to reduce FMR and compares favorably with the Ideal Device Profile. However, more development is needed.
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• Cordis Corporation
• INSCOPE® Multi‐Clip Applier team (Ethicon Endo‐Surgery, Inc.)
• Secant Therapeutics*
Special Acknowledgements
*Currently pursuing DPA