The conceptual premise of the proposed research is that integrating new modeling and computational approaches into the analysis of heart function will enable the development of transformative simulation-guided analytical tools for characterizing heart function in the not-too-distant future. The goal of the project is to develop multi-physics models of ventricles in normal and abnormal hearts that run efficiently on large-scale, heterogeneous computer systems. The research will focus on applying these computational tools to healthy hearts and also to those with arrhythmia or other disorders. One novel aspect of the work incorporates the direct computation of heart sounds which should significantly advance non-invasive diagnosis of diastolic dysfunction. Beyond cardiac function and heart disease, the impact of the research extends to the areas of computational biophysics, biomechanics, computer engineering and fluid mechanics, as well as to other organ systems. The research will produce an integrated array of simulation tools for electromechanical/hemodynamical modeling in normal and diseased hearts that will be made available to the broader community though effective data management. Research training of students and postdocs will contribute to a new generation of scientists and engineers who can apply computational thinking across disciplinary boundaries. Educational impact within the PIs? universities will be enhanced by translating the research into new and existing courses; impact outside the PIs institutions will be achieved via planned high-school and minority-focused outreach activities.