This project examines the use of a biocompatible and biologically inert biomaterial (polyvinyl alcohol (PVA) polymer) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the effectiveness of properties of this polymer and its effect on the heart muscle and mitral valve 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 propose to explore an innovative approach toward treating ischemic mitral regurgitation with the use of PVA polymer that has been 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 restoring mitral valve function. We plan a parallel approach of polymer material application and development with long- term in vitro testing of polymer and in vivo experimental studies using an established ovine model of ischemic mitral regurgitation. The in vivo animal experimentation will investigate the main therapeutic endpoint which effectiveness of PVA polymer injection in reducing ischemic mitral regurgitation. The in-vivo experiments will also address the biomechanical and physiological effects of the polymer injection in the beating heart with the use of hemodynamic monitoring, quantitative 3D echocardiography and sonomicrometry. MRI diffusion imaging will assess regional changes, if any, of myocardial fiber architecture. The physical and mechanical characteristics of PVA polymer will be optimized in an iterative fashion, based on data and feedback from the in-vivo animal experiments. Similarly, data from PVA testing will be shared to optimize the in-vivo application. This information sharing, inherent in the parallel design of this proposal, will foster the collaborative efforts of this multidisciplinary team.

Public Health Relevance

This grant examines an important and common cardiac valve disorder, ischemic mitral regurgitation, for which the therapies are invasive and inconsistent. The public health effects of ischemic mitral regurgitation are significant as it affects up to 20 to 30% of patients following a heart attack and up to 50% of patients with heart failure due to a cardiomyopathy. The presence of this valvular disorder is associated with a poor prognosis, doubling mortality when present. The purpose of this grant is to explore novel and less invasive therapies to treat this important valve disorder.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Evans, Frank
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Massachusetts General Hospital
United States
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Kataoka, Akihisa; Zeng, Xin; Guerrero, J Luis et al. (2018) Application of polymer-mesh device to remodel left ventricular-mitral valve apparatus in ischemic mitral regurgitation. J Thorac Cardiovasc Surg 155:1485-1493
Capoulade, Romain; Bowdish, Michael; Kron, Irving L et al. (2017) Response by Capoulade et al to Letter Regarding Article, ""Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty"". Circulation 135:e785-e786
Capoulade, Romain; Zeng, Xin; Overbey, Jessica R et al. (2016) Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty. Circulation 134:1247-1256
Zeng, Xin; Zou, Lin; Levine, Robert A et al. (2015) Efficacy of polymer injection for ischemic mitral regurgitation: persistent reduction of mitral regurgitation and attenuation of left ventricular remodeling. JACC Cardiovasc Interv 8:355-363
Zeng, Xin; Nunes, Maria Carmo P; Dent, John et al. (2014) Asymmetric versus symmetric tethering patterns in ischemic mitral regurgitation: geometric differences from three-dimensional transesophageal echocardiography. J Am Soc Echocardiogr 27:367-75
Nunes, Maria Carmo P; Tan, Timothy C; Elmariah, Sammy et al. (2014) The echo score revisited: Impact of incorporating commissural morphology and leaflet displacement to the prediction of outcome for patients undergoing percutaneous mitral valvuloplasty. Circulation 129:886-95
Dudzinski, David M; Hung, Judy (2014) Echocardiographic assessment of ischemic mitral regurgitation. Cardiovasc Ultrasound 12:46
Nunes, Maria Carmo P; Hung, Judy; Barbosa, Marcia M et al. (2013) Impact of net atrioventricular compliance on clinical outcome in mitral stenosis. Circ Cardiovasc Imaging 6:1001-8
Mehrotra, Praveen; Jansen, Katrijn; Flynn, Aidan W et al. (2013) Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis. Eur Heart J 34:1906-14
Hung, Judy; Solis, Jorge; Handschumacher, Mark D et al. (2012) Persistence of mitral regurgitation following ring annuloplasty: is the papillary muscle outside or inside the ring? J Heart Valve Dis 21:218-24

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