Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Physics

Language

English (en)

Date of Award

Summer 9-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Sándor J Kovács

Abstract

Heart failure is the most common cause of hospitalization today, and diastolic heart failure accounts for 40-50% of cases. Therefore, it is critical to identify diastolic dysfunction at a subclinical stage so that appropriate therapy can be administered before ventricular function is further, and perhaps irreversibly impaired. Basic concepts in physics such as kinematic modeling provide a unique method with which to characterize cardiovascular physiology, specifically diastolic function (DF). The advantage of an approach that is standard in physics, such as the kinematic modeling is its causal formulation that functions in contrast to correlative approaches traditionally utilized in the life sciences.

Our research group has pioneered theoretical and experimental quantitative analysis of DF in humans, using both non-invasive (echocardiography, cardiac MRI) and invasive (simultaneous catheterization-echocardiography) methods. Our group developed and validated the Parametrized Diastolic Filling (PDF) formalism which is motivated by basic physiologic principles (LV is a mechanical suction pump at the mitral valve opening) that obey Newton's Laws. PDF formalism is a kinematic model of filling employing an equation of motion, the solution of which accurately predicts all E-wave contours in accordance with the rules of damped harmonic oscillatory motion. The equation's lumped parameters--ventricular stiffness, ventricular viscoelasticity/relaxation and ventricular load--are obtained by solving the `inverse problem'. The parameters' physiologic significance and clinical utility have been repeatedly demonstrated in multiple clinical settings.

In this work we apply our kinematic modeling approach to better understand how the heart works as it fills in order to advance the relationship between physiology and mathematical modeling. Through the use of this modeling, we thereby define and validate novel, causal indexes of diastolic function such as early rapid filling energy, diastatic stiffness, and relaxation and stiffness components of E-wave deceleration time.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7HM56K3

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