Ischemic mitral regurgitation (IMR) occurs when a structurally normal mitral valve (MV) is rendered incompetent as a result of myocardial infarction induced left ventricular remodeling. IMR effects between 1.6 to 2.8 million Americans. Mitral valve repair with undersized flat ring annuloplasty has become the preferred treatment. However, recent studies have demonstrated this approach is associated with a failure rate of 30% within 6 months of surgery. Most failures result from progressive leaflet tethering and annuloplasty ring dehiscence which implicates annular and chordal stress distribution as a mechanism. These suboptimal stress profiles are due, in part, to the fact that undersized annuloplasty likely accentuates the LV remodeling process by further impairing basal LV geometry and function. The inadequacy of undersized annuloplasty results from its failure to fulfill two of Carpentier's fundamental requirements for successful mitral valve repair: it does no reestablish normal annular geometry nor does it adequately restore leaflet mobility. Preliminary work has demonstrated the promise of saddle-shaped annuloplasty and leaflet augmentation in improving IMR repair. However, there are currently no data to support a consensus as to the optimal repair technique for IMR. Therefore, we have designed the specific aims of this project to test the hypothesis that IMR repair techniques that normalize annular geometry and restore leaflet mobility will result in more durable repairs by promoting better basal LV function, less exacerbation of LV remodeling and reduced annular and chordal stress distribution. Our innovative approach to this critical clinical problem leverages our group's unique combination of surgical and engineering expertise. Using both in vivo and in vitro models of IMR in combination with novel imaging and force transducer technology, we will assess the effect annuloplasty shape and leaflet tissue augmentation on valvular force distribution. Such an experimental approach allows for the preclinical optimization of a mitral valve repair procedures for IMR so only the most promising techniques need to be tested in patients.

Public Health Relevance

Ischemic mitral regurgitation (IMR) occurs when a structurally normal mitral valve becomes incompetent as a result of myocardial infarction. IMR effects between 1.6 to 2.8 million Americans. Recent studies indicate that IMR repair procedures are significantly less durable than previously thought. This proposal uses an innovative approach to improve the success of IMR repair techniques.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL113216-01A1
Application #
8439920
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Evans, Frank
Project Start
2013-07-01
Project End
2017-03-31
Budget Start
2013-07-01
Budget End
2014-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$707,189
Indirect Cost
$177,045
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pierce, Eric L; Gentile, Javier; Siefert, Andrew W et al. (2016) Real-time recording of annuloplasty suture dehiscence reveals a potential mechanism for dehiscence cascade. J Thorac Cardiovasc Surg 152:e15-7
Pierce, Eric L; Siefert, Andrew W; Paul, Deborah M et al. (2016) How Local Annular Force and Collagen Density Govern Mitral Annuloplasty Ring Dehiscence Risk. Ann Thorac Surg 102:518-26
Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan et al. (2015) Isolated effect of geometry on mitral valve function for in silico model development. Comput Methods Biomech Biomed Engin 18:618-27
Lee, Chung-Hao; Amini, Rouzbeh; Gorman, Robert C et al. (2014) An inverse modeling approach for stress estimation in mitral valve anterior leaflet valvuloplasty for in-vivo valvular biomaterial assessment. J Biomech 47:2055-63
Rabbah, Jean-Pierre M; Siefert, Andrew W; Bolling, Steven F et al. (2014) Mitral valve annuloplasty and anterior leaflet augmentation for functional ischemic mitral regurgitation: quantitative comparison of coaptation and subvalvular tethering. J Thorac Cardiovasc Surg 148:1688-93
Witschey, Walter R T; Contijoch, Francisco; McGarvey, Jeremy R et al. (2014) Real-time magnetic resonance imaging technique for determining left ventricle pressure-volume loops. Ann Thorac Surg 97:1597-603
Siefert, Andrew W; Pierce, Eric L; Lee, Madonna et al. (2014) Suture forces in undersized mitral annuloplasty: novel device and measurements. Ann Thorac Surg 98:305-9
Clark, James E; Marber, Michael S (2013) Advancements in pressure-volume catheter technology - stress remodelling after infarction. Exp Physiol 98:614-21
Siefert, Andrew W; Touchton Jr, Steven A; McGarvey, Jeremy R et al. (2013) In-vivo mitral annuloplasty ring transducer: implications for implantation and annular downsizing. J Biomech 46:2550-3