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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Special Emphasis Panel (ZHL1-CSR-F (M1))
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Commarato, Michael
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Barnes-Jewish Hospital
Saint Louis
United States
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Lloyd, Christopher W; Shmuylovich, Leonid; Holland, Mark R et al. (2011) The diastolic function to cyclic variation of myocardial ultrasonic backscatter relation: the influence of parameterized diastolic filling (PDF) formalism determined chamber properties. Ultrasound Med Biol 37:1185-95
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Boskovski, Marko T; Shmuylovich, Leonid; Kovacs, Sandor J (2008) Transmitral flow velocity-contour variation after premature ventricular contractions: a novel test of the load-independent index of diastolic filling. Ultrasound Med Biol 34:1901-8
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Zhang, Wei; Chung, Charles S; Riordan, Matt M et al. (2007) The kinematic filling efficiency index of the left ventricle: contrasting normal vs. diabetic physiology. Ultrasound Med Biol 33:842-50
Chung, Charles S; Kovacs, Sandor J (2007) Pressure phase-plane based determination of the onset of left ventricular relaxation. Cardiovasc Eng 7:162-71
Riordan, Matt M; Kovacs, Sandor J (2007) Stiffness- and relaxation-based quantitation of radial left ventricular oscillations: elucidation of regional diastolic function mechanisms. J Appl Physiol 102:1862-70
Riordan, Matt M; Kovacs, Sandor J (2007) Absence of diastolic mitral annular oscillations is a marker for relaxation-related diastolic dysfunction. Am J Physiol Heart Circ Physiol 292:H2952-8
Shmuylovich, Leonid; Kovacs, Sandor J (2007) E-wave deceleration time may not provide an accurate determination of LV chamber stiffness if LV relaxation/viscoelasticity is unknown. Am J Physiol Heart Circ Physiol 292:H2712-20

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