This project explores the use of a novel biocompatible material (polyvinyl alcohol) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the properties of this biomaterial and its effect on the heart muscle and valvular function so that it can be used in the most effective way in patients with ischemic mitral regurgitation. Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles late mortality. The fundamental mechanism underlying ischemic mitral regurgitation is distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We have shown that this process can be reversed by re-shaping the heart surgically with plication or with an external patch; these approaches, however, immobilize a large portion of the heart and require open-heart surgery. We propose to explore an innovative approach toward achieving this goal with the use of biomaterials that are specifically designed for injection into the myocardium with subsequent crosslinking once injected. This results in myocardial tissue bulking and repositioning of the infarcted myocardial wall with relief of LV distortion and deformation, thereby assuming a more normal shape that relieves the tension on the mitral leaflets. This approach also has the potential for minimally invasive implementation such as through percutaneous delivery. To achieve this synthesis of clinical problem and developmental techniques, this proposal will bring together expertise in several areas: quantitative analysis of the mitral valve in animal models by three-dimensional echocardiography, development of a biomaterial with physical and mechanical properties adapted to relieve ischemic distortion of the ventricle (Drs. Orhun Muratoglu and Gavin Brathwaite of Biomaterials Laboratory at MGH and Cambridge Polymer Group, Inc, Charlestown, MA), MRI diffusion imaging for assessment of changes in myocardial fiber architecture :(Dr. Van Wedeen) and cardiovascular physiology and surgery (Dr. Vlahakes). ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB005294-01A1
Application #
7094689
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Moy, Peter
Project Start
2006-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$278,569
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Solis, Jorge; Levine, Robert A; Johnson, Benjamin et al. (2010) Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model. Circ Cardiovasc Interv 3:499-505
Solis, Jorge; Sitges, Marta; Levine, Robert A et al. (2009) Three-dimensional echocardiography. New possibilities in mitral valve assessment. Rev Esp Cardiol 62:188-98
Chua, Sarah; Levine, Robert A; Yosefy, Chaim et al. (2009) Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views. Eur J Echocardiogr 10:619-24
Chaput, Miguel; Handschumacher, Mark D; Guerrero, J Luis et al. (2009) Mitral leaflet adaptation to ventricular remodeling: prospective changes in a model of ischemic mitral regurgitation. Circulation 120:S99-103
Solis, Jorge; McCarty, David; Levine, Robert A et al. (2009) Mechanism of decrease in mitral regurgitation after cardiac resynchronization therapy: optimization of the force-balance relationship. Circ Cardiovasc Imaging 2:444-50
Neilan, Tomas G; Ton-Nu, Thanh-Thao; Kawase, Yoshiaki et al. (2008) Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes. Am J Physiol Heart Circ Physiol 294:H2106-11
Chu, John W; Levine, Robert A; Chua, Sarah et al. (2008) Assessing mitral valve area and orifice geometry in calcific mitral stenosis: a new solution by real-time three-dimensional echocardiography. J Am Soc Echocardiogr 21:1006-9
Poh, Kian Keong; Levine, Robert A; Solis, Jorge et al. (2008) Assessing aortic valve area in aortic stenosis by continuity equation: a novel approach using real-time three-dimensional echocardiography. Eur Heart J 29:2526-35
Hung, Judy; Solis, Jorge; Guerrero, J Luis et al. (2008) A novel approach for reducing ischemic mitral regurgitation by injection of a polymer to reverse remodel and reposition displaced papillary muscles. Circulation 118:S263-9

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