1. Transcatheter Mitral Valve Replacement
Howard C. Herrmann, MD
University of Pennsylvania
Philadelphia
Grant/Research Support: Edwards Lifesciences, Inc.
Evalve, Inc.
Consulting, Equity Interest: Endovalve, Inc.

2. Background
Efficacy and risks of surgical mitral valve replacement are well understood
Better reduction in MR than repair
Not all patient populations, disease etiologies, anatomical variations will be compatible with repair
Risks equivalent to repair in functional etiology, higher-risk, older patients with current generation of bioprostheses and complete valve-sparing operations
However surgical MVR has significant morbidity and mortality due to risks of incision and CPB
Percutaneous repair is nicer than surgery, but it isn’t surgery
“Modified” surgical techniques
Annular ring approaches have unclear efficacy and risks of erosion, perforation, coronary artery thrombosis
Edge-to-edge repair is technically demanding, limited to a subset of patients, and long-term durability still under investigation
Combinations of repair technologies may be necessary
Surgeons have a more robust toolbox when deciding how to repair a valve
Increasing evidence that percutaneous approaches are more limited than surgical techniques and unlikely to achieve equal efficacy
For these reasons we believe it is important to offer clinicians and patients a less invasive, valve-sparing means of performing a MV replacement

3. Mehta R. H. et al.; Ann Thorac Surg 2002;74:1459-1467
Mortality by age for low-risk, medium-risk, and high-risk categories of patients undergoing surgical mitral valve replacement
STS Database: 31,688 pts
Use of bio-prostheses:
20% (<50 yrs) to 80% (>80 yrs)
Mortality risk increased with age:
4.1% (<50 yrs) to 17.0% (>80 yrs)
Morbidity (stroke, prolong vent, reop, renal failure, sternal infection) increased with age:
13.5% (<50 yrs) to 35.5% (>80 yrs)
Multivariable predictors M&M:
Age, hemo instability, NYHA IV, renal failure, CABG
> 10% Mortality
Mehta R. H. et al.; Ann Thorac Surg 2002;74:

4. Mitral Pericardial Bioprosthesis (Edwards PERIMOUNT)
> 70 yrs
> 65 yrs
> 60 yrs
< 60 yrs

5. Evaluation of Outcomes Following Mitral Valve Repair vs Replacement in Severe Ischemic MR (NIH Sponsored CT Surgery Network Research Group Study)
250 subjects with severe MR (ERO > 0.4 cm2) (+ CABG)
MV repair (annuloplasty w subvalv procedure if severe tethering)
MV replacement with complete subvalvular preservation
1° endpoint = LV remodeling (LVESVI) at 12 mos
Statistical power 90% to detect 15 ml/m2 diff in LVESVI between groups (15% additional reduction after 20%)
2° endpoint = mortality, functional status, QOL, etc.
Highlights
High recurrence rate of severe MR after annuloplasty alone
Need to address subvalvular changes with repair in IMR
Lack of data comparing replacement to repair in other than observational or case series with mixed patient populations

6. Transcatheter Mitral Valve Replacement With Stent Prostheses
D. Paniagua 1
Acute human insertion of aortic prosthesis in mitral position
G. Lutter 2
Transapical off-pump insertion porcine prosthesis self-expanding nitinol stent
Acute success but 7/8 pigs died early due to:
Paravalvular leaks
Suboptimal positioning
Failure of fixation
Subsequent report of fixation to 60 min (1 death, multiple attempts to position)
Perc Cardiovasc Solutions (S. Thambar 1)
CardiAQ
1 Personal communication
2 Lozonschi et al, Ann Thorac Surg 2008;86:745; EJCTS 2009

7. Transcatheter MVR: Challenges
Delivery
Fold/compress, size (larger than aortics)
Fixation
More complex structure
No calcium to grab radially
Not a round valve
Orientation may be important
Seal
Paravalvular leak likely less well tolerated than aortic (hemolysis)
Function
LVOT obstruction a concern
Need to preserve the subvalvular apparatus

8. Endovalve Inc.
Endovalve Inc is a cardiovascular device company developing a mitral valve replacement system designed for insertion during a minimally invasive surgical (MIS) procedure
The proprietary Endovalve system is designed to allow for a complete mitral valve replacement without the risks and complications usually associated with open-heart surgery, avoiding both sternotomy and cardio-pulmonary bypass.
Clinical advantages of this approach include:
Reduction in MR as good as surgery
Takes advantage of improving durability of bioprosthetic leaflets
Fully valve-sparing (similar to repair)
Initially based on patented technology from the Univ of PA, our platform will allow for later development of a percutaneous system utilizing the same valve design.

10. Bench testing
Established baseline flow performance of first engineering prototypes
Pressure drop
Effective orifice area
Meets acceptable limits per ISO5840
Flow visualization
Image leaflets through cardiac cycle, closure characteristics
Image of open leaflets
Influence leaflet design and shape
Measure MR
Georgia Tech (Dr. Ajit Yoganathan)

11. Transcatheter Mitral Valve Replacement Engineering Prototype – Sheep Implant
No MR at 6 hours post CPB
Mean transmitral gradient = 2 mm Hg
No LVOT gradient

12. Conclusions
Minimally-invasive surgical insertion of a foldable bio-prosthetic mitral valve is feasible
Advantages of this approach include:
Avoidance of the complications of conventional cardiac surgery
Cardiopulmonary bypass
Sternotomy
Fully valve sparing
MR reduction equivalent to surgical valve replacement
Product development in process
Detailed design
Verification
Clinical validation