Heart failure is one of the most common, costly, disabling, and deadly medical conditions that affects more than 5 million Americans, generating annual health care costs of $34 billion. Despite the wide variety of pharmacological, surgical, device, and tissue engineered therapies currently under investigation, patients with heart failure continue to experience progressive weakening of the heart muscle, reduced pumping efficiency, frequent admission to the hospital, and premature death. Strategies designed to reverse strain abnormalities by providing structural support to the ventricular wall are recognized as a new paradigm to prevent disease progression. The objective of this work is to investigate the potential of passive cardiac support in heart failure using computational mechanics. Traditionally, the development of heart failure therapies has been primarily empirical rather than simulation-based. Novel continuum theories combined with modern imaging modalities and computational techniques now offer the potential to provide greater insight into the complex pathways of heart failure, and guide the design of new treatment strategies. Motivated by a recent 4D videofluoroscopic chronic ovine heart failure study performed in the laboratory of Professor Ellen Kuhl at Stanford University, the specific aims of this project are (i) to explore local alterations in fiber strains during infarct-induced remodeling using the nonlinear field theories of mechanics, (ii) to characterize the in vivo material properties and wall stress profiles during the progression of heart failure using inverse finite element analysis, and (iii) to create subject-specific test beds to virtually probe distinct passive support therapies and identify the most effective treatment strategy. The immediate deliverables from this project include: (i) a functional relationship between local cardiomyocyte overstretch and global ventricular dilation, (ii) fiber strain maps to identify akinetic and dyskinetic regions, (iii) a unique database of in vivo passive and active material property values in the beating heart, (iv) a mechanical quantification of property changes in failing hearts, (v) in vivo tension-length relationships in healthy and diseased hearts, and (vi) a sound physical understanding of passive cardiac support mechanisms. The expected long-term outcome is a subject-specific simulation tool that enables the precise prediction of global cardiac strains, local fiber strains, wall stresses, and remodeling-induced alterations in cardiac form and function.
Dao C, Tsamis A, Swanson JC, Rodriguez A, Kvitting JP, Bothe W, Kuhl E, Ingels NB, Miller DC, Liang DH. Experimental validation of circumferential and radial strains in the beating ovine heart using speckle tracking imaging. Journal of the American Society of Echocardiography. Submitted.
Tsamis A, Cheng A, Nguyen TC, Langer F, Miller DC, Kuhl E. Kinematics of cardiac growth: In vivo characterization of growth tensors and strains. Journal of the Mechanical Behavior of Biomedical Materials 8: 165-177, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22402163
Tsamis A, Bothe W, Kvitting JP, Swanson JC, Miller DC, Kuhl E. Active contraction of cardiac muscle: In vivo characterization of mechanical activation sequences in the beating heart. Journal of the Mechanical Behavior of Biomedical Materials 4(7): 1167-1176, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21783125