Projects and Grants per year
Grants and Contracts Details
Description
Treatment options for the 5.7 million Americans afflicted with heart failure remain limited, with ~50% of patients
dying within 5 years of their diagnosis. Nearly 500,000 Americans are afflicted with familial hypertrophic
cardiomyopathy and another 60,000 suffer from familial dilated cardiomyopathy, both of which are caused by
genetic mutations that alter sarcomeric proteins, such as myosin. This U01 project seeks to mitigate these dire
numbers through innovative research that could ultimately lead to the development of personalized multiscale
computer models for optimizing heart failure treatments, including pharmaceutical interventions. To accomplish
this goal, the structural scales between single myosin molecules and organ-level ventricular function, as well
as the time scales from individual heart beats to long-term ventricular remodeling will need to be bridged. We
propose to develop, calibrate, and validate a multiscale computer model that predicts how modulation at the
molecular-level, via mutation and/or pharmaceutical alteration of myosin, impacts chronic cardiac performance.
Experiments will be conducted to longitudinally measure changes in structure and function at multiple scales.
This data will drive the development and validation of multiscale growth and remodeling algorithms that, for the
first time, will be able to account for the alterations in both the structure and function of the ventricle. The
specific aims of the proposed work are to: (1) Integrate a multi-step myosin kinetic model into an organ-level
finite element framework for predicting the effects of mutation and pharmaceutical treatment, (2) Develop
growth and remodeling algorithms to model chronic changes in ventricular structure and function resulting from
mutation and pharmaceutical treatment, and (3) Calibrate and validate the multiscale model using chronic
measurements made at different spatial and temporal scales. The software and techniques developed in this
project can be used to help accelerate translational research that focuses on the long-term effects resulting
from molecular modulation of cardiac contractile function. In the future, one could envision clinicians testing
drug treatments in-silico and selecting the intervention with the greatest long-term benefit for their patient.
Status | Finished |
---|---|
Effective start/end date | 8/3/17 → 7/31/19 |
Funding
- National Heart Lung and Blood Institute: $722,478.00
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Projects
- 1 Finished
-
Multiscale Modeling of Inherited Cardiomyopathies and Therapeutic Interventions
National Heart Lung and Blood Institute
8/3/17 → 7/31/19
Project: Research project