Heart failure (HF) is a worldwide epidemic that contributes considerably to the overall cost of health care in developed nations. The number of people afflicted with this complex disease is increasing at an alarming pace-a trend that is likely to continue for many years to come. The overall goal of our proposed research is to optimize a therapy for HF that involves percutaneous injection of a hydrogel (Algisyl-LVR) in the failing myocardium. Given the cardiovascular system's complexity, a multi-disciplinary expertise across experimental and computational domains is required to fully investigate this novel HF therapy. The three specific aims include the following: First, we will validate mathematical (finite element models of failing left ventricles that have been treated with Algisyl-LVR + coronary artery bypass grafting or Algisyl-LVR alone. The finite element models will have realistic 3D geometries based on magnetic resonance imaging and validated with in-vivo myocardial strain versus left and right ventricular pressure measurements. Additionally, ex-vivo 3D myofiber orientation and direct force measurements in skinned fiber preparations will be made. Second, we will use the validated finite element models and our method for automatically optimizing medical devices for treating HF to design the optimal Algisyl-LVR injection pattern and test it in swine with systolic HF. Lastly, we will deliver Algisyl-LVR percutaneously, using the optimal injection pattern determined in Aim 2, and test it in swine with systolic HF. The proposed approach and methodologies are innovative in simulation of animal-specific device therapy that holds very significant promise for treatment of the epidemic of HF.

Public Health Relevance

Medical and/or surgical treatment of cardiovascular disease, especially heart failure, stands to vastly improve both the longevity and quality of life. Magnetic resonance imaging (MRI) with heart tissue tagging or cardiac tagged MRI combined with physics-based mathematical (finite element) modeling allows for non-invasive quantification of heart wall mechanical properties. If these mechanical properties can be correlated to disease state and the potential effect of therapeutic intervention, then the cardiology community will be able to add a significant new methodology to its armamentarium regarding patient care protocols and in particular the surgical treatment of heart failure as is the focus of this proposa.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL118627-01
Application #
8480136
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Lee, Albert
Project Start
2013-09-01
Project End
2017-06-30
Budget Start
2013-09-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$779,694
Indirect Cost
$119,925
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
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Genet, M; Rausch, M K; Lee, L C et al. (2015) Heterogeneous growth-induced prestrain in the heart. J Biomech 48:2080-9

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