Heart failure is a deadly epidemic with few therapeutic options. Ventricular restraint represents a promising non-transplant treatment currently in clinical trials. In this surgery, the heart is wrapped with passive material to prevent it from dilating and remodeling. Currently, there is no methodology to measure or adjust restraint therapy level. No studies exist correlating restraint level to therapy efficacy or mechanism. Therapy is applied subjectively. This may ultimately limit overall effectiveness and impair safety. To address this, an adjustable, fluid-filled balloon was developed to quantitatively apply restraint to the entire ventricular epicardial surface. The long-term goals of this project are to quantitate how ventricular restraint influences the remodeling process and to identify rational criteria for improved therapy efficacy by applying restraint in a measurable and adjustable manner. By applying measurable, adjustable restraint with this unique restraint device to an ischemic ovine model of dilated cardiomyopathy, Specific Aim #1 will measure the acute and subacute effects of restraint level on remodeling pathophysiology.
In Specific Aim #2, the chronic effects of restraint on remodeling will be quantitated, and an optimal restraint level will be identified.
Specific Aim #3 will investigate whether measurable, adjustable restraint therapy results in increased reverse remodeling compared to standard, non-adjustable restraint therapy.
These specific aims are designed to provide a comprehensive quantification of the effect of restraint level on ventricular pathophysiology and remodeling. By measuring cause and effect with respect to restraint and reverse remodeling for the first time, these studies may provide an entire new approach to ventricular restraint that may lead to significant advance in the armamentarium against heart failure. Heart failure is an epidemic with few therapeutic options. Ventricular restraint is a promising non-transplant surgical option currently in clinical trials. This proposal seeks to better understand and improve restraint therapy for patients by adjusting and measuring the applied restraint level.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL090862-05
Application #
8209143
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Schwartz, Lisa
Project Start
2008-01-07
Project End
2014-02-28
Budget Start
2012-01-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2012
Total Cost
$391,022
Indirect Cost
$136,921
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Cevasco, Marisa; Kwon, Michael; Fiedler, Amy et al. (2014) Right heart failure: an ischemic model and restraint therapy for treatment. Ann Thorac Surg 97:1356-62; discussion 1362-3
Lee, Lawrence S; Ghanta, Ravi K; Mokashi, Suyog A et al. (2013) Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy. J Thorac Cardiovasc Surg 145:824-31
Mokashi, Suyog A; Lee, Lawrence S; Schmitto, Jan D et al. (2013) Restraint to the left ventricle alone is superior to standard restraint. J Thorac Cardiovasc Surg 146:192-7
Mokashi, Suyog A; Guan, Jian; Wang, Dahai et al. (2010) Preventing cardiac remodeling: the combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia. J Thorac Cardiovasc Surg 140:1374-80
Lee, Lawrence S; Ghanta, Ravi K; Mokashi, Suyog A et al. (2010) Ventricular restraint therapy for heart failure: the right ventricle is different from the left ventricle. J Thorac Cardiovasc Surg 139:1012-8
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