We hypothesize that LV filling dynamics are altered in patient groups known to have cardiac dysfunction (ie. HF with EF >0.50, HF with EF <0.40, and LV hypertrophy) compared to normals. These alterations are manifested by a reduction of the initial Vp and reduction of the distance from the mitral valve to the point where the deceleration occurs. The relationship between the deceleration of the filling wave and the onset of the adverse pressure gradient within the LV establishes the physical mechanism governing the filling. In addition we hypothesize that a novel parameter, the early filling strength (Vs), that combines the initial Vp and the deceleration distance, better separates these patient groups from normals compared to conventional measures of diastolic function (i.e. VP, e , E/e , or iso-volumetric strain rate). Our preliminary work demonstrates the feasibility of our proposal, and our initial observations are consistent with our hypotheses. We will explore the above hypothesis by pursuing the following specific aims: 1) Automate the CMM analysis to objectively assess diastolic filling and eliminate inter-operator variability. In our preliminary work we have accomplished this by using a semi-automated algorithm analyzing single heartbeats. We will now extend this method to automatically assess data from multiple beats, improving the ease of use and accuracy of the analysis. 2) Develop a physics-based method for characterizing diastolic filling by measuring the velocity of flow propagation and its temporal variations and assessing the intraventricular pressure gradients from clinically obtained CMM echocardiograms. 3) Assess early diastolic flow propagation velocities and intraventricular pressure gradients in a prospective study that will include healthy patients and diseased patients both with preserved and reduced EF, allowing us to test our hypothesis regarding the physical basis for normal and abnormal early diastolic LV filling and compare to conventional measures of diastolic function (i.e. Vp, e', E/e', isovolumetric strain rate).

Public Health Relevance

The goal of this project is to overcome limitations with the accurate estimation of the propagation velocity and delineate the filling mechanics related to Vp. Subsequently, utilize this knowledge to develop a physically consistent, accurate and robust methodology for quantifying the early diastolic filling. A new parameter, the early filling strength (Vs), that combines the initial Vp and the deceleration distance, will be developed and we will show that it better separates patient groups from normals. Success in this effort will allow better insight in the physics of diastolic dysfunction and will re-assert Vp as a reliable metric that will work in concert with other diagnostic parameters.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL106276-02
Application #
8309025
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Adhikari, Bishow B
Project Start
2011-08-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$184,541
Indirect Cost
$27,288
Name
Virginia Polytechnic Institute and State University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061
Charonko, John J; Kumar, Rahul; Stewart, Kelley et al. (2013) Vortices formed on the mitral valve tips aid normal left ventricular filling. Ann Biomed Eng 41:1049-61
Iwano, Hiroyuki; Little, William C (2013) Heart failure: what does ejection fraction have to do with it? J Cardiol 62:1-3
Ohara, Takahiro; Ohte, Nobuyuki; Little, William C (2012) Pulmonary hypertension in heart failure with preserved left ventricular ejection fraction: diagnosis and management. Curr Opin Cardiol 27:281-7
Kitzman, Dalane W; Little, William C (2012) Left ventricle diastolic dysfunction and prognosis. Circulation 125:743-5