1. MITRALIGN: Direct Annuloplasty
CRT 2010
Washington DC, January 21, 2010
MITRALIGN: Direct Annuloplasty
Device Evolution, Technique and
Clinical Trial Update
Eberhard Grube, MD, FACC, FSCAI
St.Elisabeth Hospital, Heart Center Rhein-Ruhr, Essen, Germany
Instituto Cardiologico Dante Pazzanese, São Paulo, Brazil

2. Eberhard Grube, MD DISCLOSURES Consulting Fees Honoraria
Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson Company, Medtronic CardioVascular, Inc.
Honoraria
Biosensors International , Boston Scientific Corporation, Medtronic CardioVascular, Inc
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Biosensors International , Medtronic CardioVascular, Inc.
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference off-label use of stents and valve prosthesis.

3. Disclosure Eberhard Grube, MD Mitralign: C
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 Mitralign: C
Key
G – Grant and or Research Support E – Equity Interests S - Salary
C – Consulting fees, Honoraria R – Royalty Income I – Intellectual Property Rights
SB – Speaker’s Bureau O – Ownership OF – Other Financial Benefits‘ 3

4. MITRALIGN Concept
Surgical approaches for treatment of FMR are focused on size reduction of the mitral valve annulus.
A relatively small (1 cm) plication of the posterior annulus can normalize the septo-lateral dimension and reduce MR.
Mitralign concept emulates suture annuloplasty.
Retrograde LV approach
Surgical pledgets are delivered percutaneously through the posterior annulus
Plicate the annulus

5. Trident Design 12.5 Fr. Guide Catheter Steerable catheter
provide ventricular access for all catheters
Steerable catheter
access mitral annulus at P2 center
deliver crossing wire (RF) to penetrate the annulus
A triple lumen catheter (Trident)
advanced over the P2 crossing wire
provide positioning of P1 and P3 locations
deliver P1 and P2 crossing wires to penetrate the annulus
Pledget delivery catheter
tracked over a crossing wire through the annulus
deliver the pledget
Plication catheter
plicate by exerting tension via the sutures
deploy a stainless steel lock to lock the three sutures
Suture cutter
cut the sutures following deployment of the lock

6. Concept Annular Plication
Mitralign Concept
Interventional surrogate of surgical suture annuloplasty
Anchors are placed along the posterior annulus
Plication using these anchores, herewith reducing the circumference which restores leaflet coaptation P3 P1 P2
Concept Annular Plication 6

7. First in Man Experience Paraguay
Pre-Plication
Final Implant P1 P2 P3 P1 P2 P3
Baseline
12 months FU MR 3+ 2+
EDV (ml)
168
115
ESV (ml) 85
MVA (cm2)
4.0
2.83
NYHA
III I

8. Trident Concept First in Man Experience
Four patients implanted in Paraguay by Dr. A. Ebner
3 patients with all 3 pledgets
1 patient with 2 pledges only
Surgical pledgets can be delivered through the mitral annulus
Mitralign approach can be developed further
Difficult to manage 3 components (wires, pledgets and sutures) at the same time:
Simpler design is needed

9. New MITRALIGN Design Bident Catheter
A double lumen catheter (Bident) to be advanced over a crossing wire and to provide positioning of a pair of wires
Two pairs of pledgets to be delivered in
P1-P2 location
P2-P3 location
Span of the bident catheter available:
1.4 cm or
1.7 cm.

10. MITRALIGN Bident Design Permanent Implants
Atrial Side
Ventricle Side
Two plications in two locations: P1-P2 and P2-P3
Minimum permanent implants
4 surgical pledgets
2 locks to lock the sutures after plication

11. Mitralign System Steerable Guide Steerable Wire Delivery Catheter
Crossing Wire
Translation Catheter
Pledget Delivery Catheter
Plication Lock and Cut Catheter

12. Bench Test: Bident vs. Trident
Before Plication
After Plication
20 mm
16 mm
TRIDENT
27mm
26 mm
20 mm
12 mm
BIDENT
27 mm
22 mm
Bident 2x2 plication outperforms Trident plication

13. Pre-Clinical Study: Bident
MITRALIGN Bident Design simplifies the procedure.

14. Normal Healing Response 30 Days After Implantation

15. 30-Day Histology

16. Finite Element Analysis: Trident vs Bident
Model
Initial Position
Plication
TRIDENT
BIDENT
Model
SL distance (mm)
CC-distance (mm)
MVA (cm2)
Baseline
27.6
43.1
9.50
TRIDENT plication
26.6
44.4
8.30
BIDENT– 2x2 plication
23.5
39.9
7.43
Bident 2x2 plication outperforms Trident plication

17. Finite Element Analysis Selecting Bident Location
Control
Placement
Plication
MR due to annulus dilatation
Intermediate placement of pledgets in P2/P1 and P2/P3 seems to be the best
Plication causes an anterior displacement of the posterior wall of 5-10 mm

18. Mitralign FIM Studies South America and Europe
Phase I
(Trident)
Phase II
(Bident)
Device optimization
in Paraguay
Limited number of implanted patients (n=4)
One patient with complete FU at 1 year
Significant changes in the MPAS
Feasibility and safety of Bident MPAS (optimized design)
12 patients to be enrolled at 4 sites
Echo Core Lab
Primary objective:
- to assess the safety and feasibility of MPAS for treatment of FMR
Primary enpoint:
- Device related NACE (net adverse clinical events) at 30 days. Device-related NACE include: Death, MI, Cardiac tamponade, Cardiac surgery, Stroke

19. Bident FIM Study Clinical Sites
Study PI:
Eberhard Grube, MD
Study sites and Site PIs
St.Elisabeth Krankenhaus,Heart Center Rhein-Ruhr
Dr. E. Grube
Helios Heart Center, Siegburg, Germany:
Dr. L. Buellesfeld
Asklepios Klinik St. Georg, Hamburg, Germany:
Dr. K.H. Kuck
Dante Pazzanesse Cardiology Center, Sao Paulo, Brazil:
Drs. A. Abizaid, C. Esteves, E. Grube
Klinikum-Oldenburg, Oldenburg, Germany:
Dr. A. Elsaesser
Echo Core Lab
MedStar, Washington , DC, USA
Dr. Neil Weissman

20. Inclusion Criteria Patient is ≥18 years old
Functional Mitral Regurgitation ≥ 2+
NYHA Class: II-IV
EF% ≥ 30%
Mitral plane to apex dimension ≥ 5 cm
Structurally normal mitral valve
No significant calcification
No thrombus in LV or LA

21. Conclusions
Mitralign Percutaneous Annuloplasty System is emerging technology for direct annuloplasty.
First experience with the Trident System was promising but change in design concept was needed.
To simplify the procedure
To possibly improve outcomes
Safety and feasibility of the new Bident System will be studied in the new FIM study in Germany and Brazil.

22. Thank you for your attention !