Despite recent advances in the treatment of human heart failure, the overall impact on morbidity and mortality has been limited and heart failure remains the preeminent cardiovascular health problem is this country. In particular, right ventricular (RV) dysfunction is implicated in nearly 20% of all deaths associated with congestive heart failure. The proposed research will focus on three models of heart failure: RV pressure overload, RV volume overload, and RV ischemia. Cardiac surgery procedures, including heart transplantation, may be associated with any or all of these conditions. Failure to recognize and quantitatively assess RV dysfunction can result in fatal perioperative RV depression. Limitations in our understanding can be attributed to the paucity of information concerning right heart function and the lack of mathematical and engineering models for the analysis of RV performance. Thus, the primary aim of the proposed research is to develop and apply state-of- the-art methods of instrumentation and mathematical/engineering analyses to improve quantitative assessment of right ventricular diastolic function, dysfunction and failure. A secondary aim is to provide definitive cardiodynamic indices of RV diastolic dysfunction. Main hypotheses to be addressed include: 1. RV relaxation abnormalities are associated with RV dysfunction and heart failure. 2. RV diastolic pressure-volume relations reflect the progressive pathogenesis of RV hypertrophy and failure. 3. RV filling patterns in heart failure depend on specific diastolic myocardial, loading and geometric abnormalities. Micromanometric, sonomicrometric, and velocimetric measurements will be obtained in chronic closed-chest swine experiments. Echocardiography and magnetic resonance imaging techniques will be used to further develop RV geometric volume models and to identify geometric derangements. The severity and extension of myocardial ischemia will be assessed by SPECT. These large animal model data will be used to validate the biomechanical, mathematical and computational models of RV diastolic function which will be developed. The facilities for cardiac research at Duke University are outstanding, and the investigators involved in the proposed studies have a history of strong collaboration, work in close proximity and have all the necessary tools to fulfill the goals of the research program, including access to supercomputers at NCSC.
Showing the most recent 10 out of 23 publications
