Contact PD/PI: GORMAN, JOSEPH Ischemic Mitral Regurgitation (IMR) is a major clinical problem. Our group has demonstrated that IMR is a heterogeneous disease with two general subpopulations.(1) In one group, IMR results from moderate annular dilatation and profound leaflet tethering. We have shown these patients are best treated by valve replacement.(1, 2) In the second subpopulation, IMR is the result of severe annular dilatation (i.e. minimal leaflet tethering). Here, ring annuloplasty has been shown to be an effective treatment, provided the ring remains anchored to the annulus. The Achilles heel of these repairs is the higher suture forces required to downsize these large annuli, which predisposes to dehiscence. Ring dehiscence is estimated to underlie 13- 42% of reoperations for procedure-related repair failures.(3-5) Dehiscence occurs when the suture holding strength of the local tissue is exceeded by the force on the suture. We have developed novel transducers to measure ring suture force and quantified the effects of ring type, sizing, suture position, annular histology, and holding strength on dehiscence likelihood.(6-9) These studies have mechanistically demonstrated that ring flexibility significantly reduces suture forces, specifically in the weakest region of annular tissue. These results suggest that the incorporation of segmental ring flexibility to the already known functional benefits of saddle shape will produce IMR-specific rings that restore valve geometry while reducing dehiscence likelihood even in the setting of suboptimal suture placement. To this end, the following specific aims have been designed to prove the hypothesis: In the setting of IMR, new hybrid rigid-flexible annuloplasty rings are capable of both restoring normal valve geometry and reducing ring suture forces to a magnitude that overcomes the effect of suboptimal suture placement that otherwise would lead to an increased likelihood for dehiscence.

Public Health Relevance

Surgical repair has become the treatment of choice for mitral regurgitation. Ring annuloplasty is a key component of all repairs. Ring dehiscence has become an increasingly recognized form of repair failure. We have established regional material properties (i.e. ring flexibility) as the singular ring design parameter that can reduce dehiscence likelihood. We hypothesize that saddle shaped rings with regionally heterogeneous material properties will optimize annuloplasty by reducing dehiscence likelihood and maintaining normal leaflet geometry.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL147256-03
Application #
10155588
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Evans, Frank
Project Start
2019-04-01
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104