This revised application for a Midcareer Investigator Award in Patient- Oriented Research focuses on quantitative cardiac physiology in clinical cardiology. The goal is to mentor young investigators in multi- disciplinary clinical investigation aimed at maximizing the amount of useful information extracted. The applicant has an established record of mentoring. In 1991 he founded Washington University's Cardiovascular Biophysics Laboratory in part to serve as a training and hypothesis- testing venue for patient-oriented research. Trainees will be exposed to ongoing investigations that use novel methods to explore mechanisms of human disease (congestive heart failure, systolic and diastolic dysfunction) and elucidate physiology (four-chamber heart function). Main themes of investigations include: diastolic function assessment by Doppler echocardiography via model-based image processing (MBIP); four chamber equilibrium volume determination by cardiac MRI; and hemodynamic characterization by phase-plane analysis. The intrinsically multi-disciplinary methods include clinical, cognitive, and quantitative tools for testing causal and correlative hypotheses. Trainees' support is via the Cardiovascular Division's training grant (NIH: 5-T32-HL07081, M.E. Cain, PI). They will formulate hypotheses that require quantitative characterization of cardiac physiology via acquisition and processing of multi-channel physiological data, and test them via application of statistical methods and determination of clinical correlates. As part of the Research Plan, one completed, funded, retrospective pilot project and its natural prospective extension are described in which trainees will participate. The hypothesis project and its natural prospective extension are described in which trainees will participate. The hypothesis tested is that Doppler derived indexes of diastolic function generated by MBIP (a novel approach) are better indicators of 1-year mortality in selected elderly patients admitted to the hospital with heart failure than are conventional echocardiographic indexes (EF, deceleration time) from the same Doppler data.
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