Approximately 7.9 million Americans suffer from heart failure every year. Among these, nearly 2.5 million develop Ischemic Mitral Regurgitation (IMR), a 33% increase since 1995. Even with such high prevalence, little is known of the cause and progression of chronic IMR, resulting in the current lack of effective medical options for these patients. What is known for certain is that IMR is secondary to gross three dimensional geometric alterations of the patient's Left Ventricle (LV), resulting in alterations in the geometry of the Mitral Valve (MV). Present surgical repair techniques to restore native LV and MV geometries lack satisfactory long-term patient outcomes. Consequently, long-term survival rates for IMR are poor and worse as compared to many types of cancer. The most important reason for the poor outcome is the lack of knowledge of the exact 3D geometric alterations of the patient's MV responsible for IMR, without which appropriate surgical treatment is not possible. The objective of this proposal is to delineate and understand the geometric distortions of the MV that lead to IMR and develop appropriate repair procedures that can be directly translated to clinical practice in the near future. The central hypothesis driving our long objectives is: Ischemic Mitral Regurgitation is strongly related to geometric alterations of the native mitral valve at the annular and/or sub-valvular levels. Understanding these alterations will clarify the geometric determinants of Ischemic Mitral Regurgitation and will help in designing better and efficient repair procedures thus leading to better surgical outcomes. Our hypothesis has been formulated based on strong preliminary data produced in our laboratories at Georgia Tech and the University of Pennsylvania. The proposed study consists of a sophisticated methodology combining in-vitro and in-vivo approaches to design an efficient IMR model that can not only test the hypothesis but also develop novel surgical approaches. The in-vivo model of IMR though effective is very reproducible and mimics only one representation of the human IMR disease. The in-vitro IMR model is a versatile model that provides precise control over the geometric distortions imposed on the valve. Also, the in-vitro model will be a potential test-bed with additional studies (beyond the currently proposed 2 year experiments) for developing novel MV surgical repair techniques that may be easily translated to clinical practice.

Public Health Relevance

Approximately 8 million Americans suffer from heart failure, of which 2.5 million have mitral valve dysfunction. Mitral valve failure is a common symptom of congestive heart failure and valve replacement was the procedure of choice. However, clinical data report high mortality rates. It is now accepted in the cardiac surgery community that repairing the mitral valve is a better choice than replacing it. But these repairs are not durable and show sub-optimal long term results. The primary objective of this proposal is to understand the effects of geometric alterations on the mitral valve and develop novel repair techniques using a combination of bench testing and animal studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL090661-01A2
Application #
7727112
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Evans, Frank
Project Start
2009-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$394,311
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
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
Padala, Muralidhar; Sweet, Michael; Hooson, Sarah et al. (2014) Hemodynamic comparison of mitral valve repair: techniques for a flail anterior leaflet. J Heart Valve Dis 23:171-6
Siefert, Andrew W; Rabbah, Jean-Pierre M; Pierce, Eric L et al. (2014) Quantitative Evaluation of Annuloplasty on Mitral Valve Chordae Tendineae Forces to Supplement Surgical Planning Model Development. Cardiovasc Eng Technol 5:35-43
Padala, Muralidhar; Gyoneva, Lazarina I; Thourani, Vinod H et al. (2014) Impact of mitral valve geometry on hemodynamic efficacy of surgical repair in secondary mitral regurgitation. J Heart Valve Dis 23:79-87
Siefert, Andrew W; Icenogle, David A; Rabbah, Jean-Pierre M et al. (2013) Accuracy of a mitral valve segmentation method using J-splines for real-time 3D echocardiography data. Ann Biomed Eng 41:1258-68
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
Siefert, Andrew W; Rabbah, Jean Pierre M; Koomalsingh, Kevin J et al. (2013) In vitro mitral valve simulator mimics systolic valvular function of chronic ischemic mitral regurgitation ovine model. Ann Thorac Surg 95:825-30
Herrmann, Tarrah A; Siefert, Andrew W; Pressman, Gregg S et al. (2013) In vitro comparison of Doppler and catheter-measured pressure gradients in 3D models of mitral valve calcification. J Biomech Eng 135:94502
Padala, Muralidhar; Cardinau, Benedicte; Gyoneva, Lazarina I et al. (2013) Comparison of artificial neochordae and native chordal transfer in the repair of a flail posterior mitral leaflet: an experimental study. Ann Thorac Surg 95:629-33
Padala, Muralidhar; Gyoneva, Lazarina; Yoganathan, Ajit P (2012) Effect of anterior strut chordal transection on the force distribution on the marginal chordae of the mitral valve. J Thorac Cardiovasc Surg 144:624-633.e2

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