2009 Research Award Winners

2009 ASE Research Awards
 
The ASE Foundation is pleased to announce the recipients of the 2009 ASE Research Awards. Through its annual research award program, the ASE Foundation supports innovative echocardiographic research activities that demonstrate the key role cardiovascular ultrasound plays in the diagnosis and management of patients with heart and vascular disease, and the role of emerging ultrasound technologies, such as 3D, contrast and hand-carried ultrasound, and their application to patient care. Awards are funded for one year beginning July 1, 2009.
 
 
2009 Cardiovascular Sonographer Research Award
Awarded to support the growth and development of basic and clinical sonographer research.
 
Ann Liner, RDCS, FASE, University Hospitals of Cleveland, Cleveland, OH – "Echocardiographic Assessment of Hypertrophic Cardiomyopathy Induced by Overexpression of C-Myc" – Read the abstract
 
 
2009 Echo Investigator Awards
Awarded to support a qualified physician or scientist performing meritorious and innovative research.
 
Jeanne DeCara, MD, FASE, University of Chicago Medical Center, Chicago, IL – "Determining the Genetics of Atherosclerosis Using a Vascular Ultrasound Phenotype" – Read the abstract
 
Judy Hung, MD, FASE, Massachusetts General Hospital, Boston, MA – "Polymer Injection Therapy for Treatment of Ischemic Mitral Regurgitation" – Read the abstract
 
 
 
 
 
 
 
 
 
 
 
 
 
Ann Liner, RDCS, FASE
University Hospitals of Cleveland, Cleveland, OH
 
Echocardiographic Assessment of Hypertrophic Cardiomyopathy Induced by Overexpression of C-Myc
 
Project Summary:
The objectives of these studies are to understand the role that cell cycle-related changes play in the development of cardiomyopathy and the ability of sophisticated echocardiographic measurements of myocardial motion to detect changes in ventricular function during that progression. To that end, we developed a conditional mouse model (MHC-MYC) that expresses the potent oncogene cell cycle-inducer, MYC, in a cardiomyocyte-specific manner. In our preliminary studies, MYC expression drives cardiomyocytes to enter the cell cycle, leads to pronounced hypertrophy and, ultimately, to death from heart failure. These findings led us to develop a novel “Cell Cycle Hypothesis” that predicts that cardiomyopathy, like cancer, is a disease of inappropriate cell cycle control. Importantly, early and transient MYC expression has been reported in various animal models of cardiomyopathy as well as in human disease; however, its functional role in pathogenesis is less clear. Importantly, MYC is potentially able to activate “pro-myopathic” pathways independent of cell cycle activation. Accordingly, the Specific Aims of this study are to examine the causal relationship between temporal expression patterns of MYC, hypertrophy, and heart failure (as determined echocardiographically and pathologically), and to use specific cell-cycle inhibitors to determine the effects of pharmacologic cell-cycle inhibition on these changes in MHC-MYC transgenic mice. In these aims, we will determine the ability of myocardial tissue motion, strain, and strain rate using velocity-vector imaging to provide insight into early and more subtle abnormalities of dysregulated myocardial function. The MHC-MYC mouse model provides an ideal tool to address these questions since the temporal expression of MYC (On & Off) can be easily regulated by doxycycline and cell cycle inhibition, and thus allow LV dysfunction to be titrated and assayed with sensitive measurements derived from velocity-vector imaging.
 
 
 
Jeanne DeCara, MD, FASE
University of Chicago Medical Center, Chicago, IL
 
Determining the Genetics of Atherosclerosis Using a Vascular Ultrasound Phenotype
 
Project Summary:
The health and economic impact of atherosclerosis on US and worldwide populations is significant. Early identification and treatment of risk factors is imperative. Unlike traditional cardiac risk factors, genetic risk factors for atherosclerosis are not incorporated into commonly used risk assessment models. Instead, genetic risk is merely inferred from family history. In this proposal we will identify genetic risk factors for atherosclerosis. We will use an ultrasound-acquired measurement, carotid intima-media thickness, as marker of atherosclerosis. This marker is heritable, suggesting that atherosclerosis has a genetic component. We will perform our studies in the Hutterites, an inbred population living on communal farms in Minnesota. Their uniquely uniform environment minimizes the variation in environmental risk factors for atherosclerosis, likely making the effect of genetic variation in atherosclerotic risk more evident. Our ultimate goal is to identify novel genes that contribute to atherosclerosis and, in the future, incorporate these genetic factors into models of disease risk.
To accomplish this, we request funds to increase our sample size of phenotyped individuals, which will provide additional power to detect atherosclerosis-susceptibility genes. To date, we have extensively defined cardiovascular traits for 460 Hutterites. If this proposal is funded, we will be able to collect, process, and analyze data from an additional 300 Hutterites during a multi-day research field trip to the Hutterite colonies in Minnesota in the summer of 2009. We are confident that this cumulative dataset will enable us to detect atherosclerosis-related genes in the Hutterites and set the stage to validate our findings in a non-Hutterite population.
 
 
 
Judy Hung, MD, FASE
Massachusetts General Hospital, Boston, MA
 
Polymer Injection Therapy for Treatment of Ischemic Mitral Regurgitation
 
Project Summary:
This project examines the use of a biocompatible and biologically inert biomaterial (polyvinyl alcohol (PVA) polymer) for treatment of ischemic mitral regurgitation. Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles late mortality. The fundamental mechanism underlying ischemic mitral regurgitation is distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We plan to test PVA polymer application in an established ovine model of ischemic mitral regurgitation, examining both acute and chronic ischemic MR.

The main objective of this proposal is to examine whether ischemic mitral regurgitation can be relieved by injection of a polymer (polyvinyl alcohol-PVA) that has been formulated specifically for this application, into the infarcted myocardium overlying the papillary muscles. Secondary objectives are to test the hypothesis that the polymer reduces MR by the following mechanisms: 1) by acting as a tissue strengthening and bulking agent to repositioning the papillary muscles and 2) injection of a polymer results in improved ventricular mechanics as reinforcement of the akinetic or dyskinetic myocardial wall, leads to improved regional and global mechanics of the remaining myocardium. The application of polymer therapy in order to reverse remodel the ventricle provides a unique opportunity to develop a less invasive and adjustable approach toward this important valvular disorder.
Advances in polymer chemistry have led to a tremendous variety of polymers, that can be selected and modified based on their physical properties and suitability for use in biologic systems. Polyvinyl alcohol (PVA) polymer is highly water-soluble and elicits little or no host biological response when implanted in animals.14-16 For these reasons, PVA polymers are used in a variety of biomedical applications including drug delivery, cell encapsulation, artificial tears, contact lenses, and more recently as nerve cuffs.15 Furthermore, PVA polymer can be formulated in situ with physical properties that are adjustable and capable of withstanding the pulsatile loading conditions in the beating heart. PVA can be designed for injection into the myocardium with subsequent crosslinking once injected by modifying PVA concentrations and physical properties so that crosslinking occurs at or near body temperature.

This project will highlight two roles of echocardiography: as a key participating technique for guiding new cardiac therapeutic interventions that are less invasive, such as PVA polymer injection into the beating heart; and as a quantitative approach for studying regional and global ventricular remodeling and its consequences for valvular function.