1. Transcatheter mitral valve cerclage annuloplasty to treat functional mitral valve regurgitation
Robert J. Lederman, MD Division of Intramural Research National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, MD, USA
Disclosures:
No conflicts of interest.
These are non-clinical or investigational procedures.

2. Acknowledgements June-Hong Kim, MD; Pusan University, Korea
Ozgur Kocaturk, PhD; NHLBI Catheter Fab
Christina Saikus, PhD; NHLBI/Georgia Tech/Emory MSTP
Anthony Faranesh, PhD; NHLBI Imaging
Merdim Sonmez, BS; NHLBI Imaging
Venkatesh Raman, MD; NHLBI
William H. Schenke, BS, NHLBI Technologist
Victor J. Wright, BS, NHLBI Technologist
Cengizhan Ozturk, PhD, MD; Bogazici University, Istanbul
Smita Sampath, PhD; Yale University
Ann Kim, BS; NHLBI Student

3. Cerclage concepts: Functional Mitral Regurgitation
PROBLEMS
SOLUTIONS
Annular circumferential dilation
Annular circumferential tension
“Tilt” to accommodate papillary muscle
Leaflet traction

4. Cerclage concepts: Natural trajectories & “chronic total occlusion” procedures
Mitral valve
Tricuspid valve
Coronary sinus

5. Circumferential (“purse-string”) annuloplasty is not new
Glover & Davila, Circulation, 1957
We will focus on the mechanism of mitral repair that affects the majority of untreated patients who have so-called functional mitral regurgitation, associated with preserved valve leaflets.
Conventional surgical repair entails implantation of a rigid annuloplasty ring, with or without further leaflet reconstruction.
This is effective but morbid.
Our approach is inspired by work applied to rheumatic mitral disease in the era before cardiac imaging or cardiopulmonary bypass. Glover and Davila implanted pursestring sutures in beating hearts with some success.

6. Transcatheter mitral cerclage annuloplasty
The concept of mitral cerclage appears complex but is fairly simple.
We enter the coronary sinus, find a vein to introduce a guidewire into the basal septum, and then traverse a variable distance along the interventricular septum to reenter the right heart either at the ventricular or atrial side of the tricuspid valve.
We then create and fix circumferential tension by closing the loop at the coronary sinus ostium.
June-Hong Kim, et al, JACC 2009; 54:638

7. Co-registered MRI roadmaps (“XFM”)

8. 3: Microcatheter engage septal perforator
Cerclage technique
1: GCV angiogram
2: Balloon occlusion
3: Microcatheter engage septal perforator
4: Septal traversal
5: Snare
6: Snare, Tension, Lock

9. Transcatheter mitral cerclage annuloplasty
We are developing novel interventional cardiology techniques to treat functional mitral valve regurgitation.
This work-in-progess has not yet been presented publically or published.
Cerclage annuloplasty tries better to introduce circumferential tension around the mitral annulus, replicating surgical ring annuloplasty, yet overcome limitations of other coronary sinus techniques. Cerclage is insensitive to the discordant planes of the coronary sinus and mitral annulus, can protect entrapped coronary arteries, and probably will be conducted easily by interventional cardiologists without a bulky permanent prosthesis.
June-Hong Kim, et al, JACC 2009; 54:638

10. Necropsy after cerclage
Viewed from right ventricle
Anterior
septal reentry
Septum
R.Atrium

11. (-) Protection; 0-400 g Tension (+) Protection; 0-800 g TensionD
Coronary artery compression & protection
(-) Protection; g Tension
Coronary artery entrapment and protection. (A,B) show the typical great cardiac vein configuration passing outside a circumflex coronary artery branch. (C) Cerclage would compress the underlying artery. D A protection device along the cerclage suture redistributes compressive forces away from coronary artery. (E-I) circumflex coronary artery pressure during cerclage tension without (E,G) and with (F,H) a protection device in place. (E) shows angiographic stenosis (arrow) induced by cerclage and (F) the same segment during cerclage tension with a protection device (dashed arrow) in place. (G,H) shows distal coronary artery pressure (Pd, depicted in green, axis on left, mm), the aortic pressure (Pa) in red, and their ratio in yellow (axis on right, displayed as fractional flow reserve). Without a protection device (G), the distal coronary pressure falls by more than half when cerclage tension (400g) is applied. (H) With the protection device in place, there is no distal pressure drop after cerclage tension is introduced (dotted arrow) until tension is sufficiently high (solid arrow) to impede mitral valve inflow. Panels A-D courtesy of Lydia Kibiuk, NIH Medical Arts.
(+) Protection; g Tension 11

12. Immediate impact of cerclage
Regurgitation grade (1-4) I II
Categorical mitral regurgitation
p<0.01
1.7
0.8
0.7
0.5
Mitral regurgitation measured using MRI
(–) Tension
Regurgitant fraction (%) 10 20 30 40
p=0.04
(+) Tension
Quantitative (A) and qualitative (B) measures of mitral regurgitation before and application of cerclage tension.
Kim JH et al JACC 2009;54:638 12

13. Immediate impact of cerclage
Kim JH et al JACC 2009;54:638

14. Potential Pitfalls Tricuspid dysfunction Conduction system
Trabecular entrapment
Mural leaflet entrapment
Conduction system
AV node or His bundle compression

15. Serendipitous findings

16. Cerclage-Annulus Planar Mismatch Compensates for Sinus-Annular Discordance
Mitral annulus
Another serendipidous effect of the cerclage trajectory is that it compensates for the common anatomic finding that the coronary sinus can be remote from the mitral valve annulus. Because cerclage traction is directed toward the LVOT, it compensates for this sinus-annular discordance that has made other transcatheter repair approaches fail.
Cerclage Plane
Coronary Sinus

17. Reciprocal LVOT & MVA constraint by cerclage: Enhances coaptation while avoiding LVOT obstruction
Systole
Diastole
AV open
MV closed
MV open
AV closed
2.0 ± 0.3 cm
1.6 ± 0.4 cm
2.8 ± 0.4 cm
2.4 ± 0.4 cm
4.4 ± 0.5 cm
4.5 ± 0.7 cm
This phenomenon is demonstrated here.
Cerclage improves coaptation, and is associated with reciprocal enlargement of the LVOT during systole.

18. The posterior annulus tilts toward the papillary muscle, and The annulus remains mobile
Accommodation to papillary muscle traction.
Enhances leaflet coaption

19. Humans usually have suitable septal perforator veins
Human venous anatomy in vivo. (A) A pressurized venogram in a patient undergoing placement of a venous lead for cardiac resynchronization therapy. A basal septal perforator vein was evident (arrow) in all 8 patients with evaluable angiograms. (B) A CT angiogram showing a basal septal perforator vein (arrows) apparently suitable for cerclage.
Kim JH et al JACC 2009;54:638 19

20. Summary: Cerclage Annuloplasty
Circumferential tension around annulus
Treats mitral regurgitation in preclinical ischemic cardiomyopathy
Novel features
Effective despite coronary entrapment (protection device)
Effective despite distant coronary sinus (planar discordance)
Coaptation enhanced by reciprocal constraint of LVOT & Mitral annulus
Flexible cerclage can preserve annular motion & accomodate papillary traction

21. What’s next? SBIR “subsidized” clinical development
Phase I ($200k) + Phase II ($3M) direct costs
US Small Businesses (sbir.gov)
Clinical development in collaboration with NHLBI
Access to NHLBI intellectual property
Early clinical study expenses without additional direct costs
Solicitation pending 2012q1 in Federal Register or