Research
University Cardiology Associates believe that robust research activities not only advance knowledge needed to reduce the toll from heart disease but also enhance the quality of clinical care by facilitating critical thinking. Accordingly, we are committed to active research programs in multiple areas as delineated below. Please see biographical information of individual faculty for grant support and recent publications.
Philip A. Ades, M.D.
Major Research Interests
Dr. Ades' research program has had consistent NIH funding since 1988. His research focuses on methods and benefits of weight loss in obese coronary patients. Other recent projects have addressed interventions to treat and prevent disability in older patients with coronary disease. A recent review on "Cardiac Rehabilitation and the Secondary Prevention of Coronary Heart Disease" in the New England Journal defines state-of-the-art practice in cardiac rehabilitation, much of it based upon local clinical research.
Kenneth A. Brown, M.D.
Major Research Interests
Dr. Brown has published extensively in the field of nuclear cardiology as a principle investigator on original research projects as well as in reviews, editorials and textbooks. He was the first to publish data showing that nuclear imaging results predict future cardiac events and has been a major contributor to the medical literature that has established the clinical utility of nuclear myocardial perfusion imaging for defining cardiac risk in patients with known or suspected coronary artery disease. This work has had a major impact in the practice of cardiology by allowing physicians to be selective in deciding which patients require invasive procedures and revascularization.
His ongoing research interests include the use of nuclear imaging to identify high and low risk patients treated with implantable defibrillators, the use of an adenosine challenge test to determine the vasodilator responsiveness of patients recently exposed to caffeine, and the use of nuclear imaging to identify patients with diabetes mellitus who are at risk for restenosis, progression of disease and future cardiac events following coronary revascularization.
Harold Dauerman, M.D.
Major Research Interests
Dr. Dauerman has utilized both single center and multi-center registry studies to elucidate interventional cardiology treatment options for high risk patient subsets—those with in stent restenosis, bifurcation lesions, ST elevation AMI and cardiogenic shock. Currently, his research focus has been on the identification of high risk patient subsets with the use of systemic markers of inflammation, and the impact of anti-inflammatory treatment options on the outcomes after PCI in those patient groups.
William Hopkins, M.D.
Major Research Interests
In addition to providing comprehensive care to patients and their families, we are committed to advancing knowledge in the fields of congenital heart disease, pulmonary hypertension, and genetic heart disease. We have an active research program focusing on the unique physiology of cyanotic congenital heart disease in adults, the relationship between chronic hypoxia and natriuretic peptides, the relationship of pulmonary hypertension and chronic hepatitis C infections, and vascular protection in adults with Down syndrome.
Martin M. LeWinter, M.D.
Major Research Interests
Dr. LeWinter has a longstanding interest in ventricular and myocardial and ventricular function. Current areas of interest include mechanoenergetics of the myocardium in acquired heart failure and genetic models of cardiomyopathy. His goal is to use whole heart mechanoenergetic, skinned strip and in vitro motility and force analyses to provide a comprehensive understanding of abnormalities of the myofilament in disease. A second area is diastolic left ventricular function, in particular the role of the giant cytoskeleton protein titin as a determinant of left ventricular stiffness and restoring forces. A third area is the effect of diabetes on myocardial function, both calcium handing and the myofilament. These studies utilize samples of human myocardium obtained in the operating room.
Markus Meyer, M.D.
Major Research Interests
Dr. Meyer's primary research interest is mechanisms responsible for and improved treatment of heart failure. His specific focus is to elucidate the role of cellular calcium handling in heart failure.
David J. Schneider, M.D.
Major Research Interests and Accomplishments
Delineated mechanisms responsible for altered fibrinolysis in the blood of patients with diabetes. Demonstrated that the combination of hyperinsulinemia, hyperglycemia and increased concentrations of free fatty acids in blood of healthy subjects increases the concentration and activity of the primary inhibitor of fibrinolysis, plasminogen activator inhibitor type 1. In vitro studies delineated that increased concentrations in blood of insulin increase expression of PAI-1 through stabilization of mRNA. In addition demonstrated that free fatty acids increase expression of PAI-1 by increasing transcription of PAI-1 through a fatty acid response region in the 5’ untranslated region of the PAI-1 gene.
Developed a semi-quantitative method to assess plaque morphology in mice. This model has been implemented to determine the role of genetic modifications such as increased vascular smooth muscle expression of PAI-1 in the genesis of atherosclerotic lesions.
Developed and implemented a sensitive and specific assessment of platelet function that utilizes flow cytometry to characterize specific components of platelet reactivity. Utilized this methodology to demonstrate the prognostic implications of platelet reactivity and to characterize the effects of selected treatments on platelet function.
Burton E. Sobel, M.D.
Major Research Interests
Developed and validated methods by which biochemical quantification of the extent of myocardial infarction could be accomplished in vivo based on sequential analyses of concentration in plasma of macromolecules (CK, MB CK isoenzymes, and other moieties such as tryponin I and tryponin T) and applied them to determine whether the extent of infarction was an important determinant of prognosis after myocardial infarction and furthermore, whether the extent of infarction could be modified by interventions that reduce myocardial oxygen requirements or increase myocardial oxygen supply. This work has had a major impact on how patients with acute myocardial infarction are treated and led to a reduction of mortality secondary to treatments, such as thrombolysis, that were validated initially with the methods developed;
Contributed to the initial development of cardiac positron emission tomography with the use of positron-emitting radionuclides including carbon-11 labeled palmitate, the physiological fuel of myocardium, and applied it to further delineate the nature of evolution of infarction and its interdiction with interventions salvaging ischemic myocardium including coronary thrombolysis with clot-selective fibrinolytic agents;
Pioneered coronary thrombolysis with the use of the clot-selective plasminogen activator, tissue-type plasminogen activator (t-PA), in studies of cells in culture, experimental animals, and mechanistic clinical studies in patients with acute myocardial infarction with quantification of the extent of infarction by positron emission tomography and analysis of time activity curves in blood of enzymes liberated from myocardium. This work provided a foundation for subsequent large-scale, multicenter clinical trials in which Dr. Sobel played a leadership role that demonstrated the efficacy of coronary thrombolysis with clot-selective agents, heparin, and aspirin in the reduction of death associated with coronary artery disease and acute myocardial infarction;
Recently delineated altered fibrinolysis in blood and altered proteolytic activity in vessel walls as mediators of deleterious effects of hyperinsulinemia associated with insulin resistance, impaired glucose tolerance, and type 2 diabetes thereby helping to elucidate the pathophysiology of macrovascular angiopathy in type 2 diabetes. This work, coupled with results of studies demonstrating that insulin sensitizers normalize fibrinolysis in patients with type 2 diabetes, is changing the approach to their treatment directed at reducing the risk of heart attack and cardiac death.
Peter Spector, M.D.
Major Research Interests
Dr. Spector's research has focused on three areas:
Characterization of paroxysmal atrial fibrillation: development of clinical ablation for treatment of paroxysmal atrial fibrillation, single cell electrophysiology and superfused tissue physiology.
Enhancement of mapping and ablation techniques for treatment of arrhythmias following repair of complex congenital heart disease, atriotomy, accessory AV pathways.
Elucidation of potassium ion channel function as it relates to cardiac repolarization and the Long QT syndrome.
Marc D. Tischler, M.D.
Major Research Interests
Research in the Echocardiography Laboratory has focused on the natural history and pathophysiology of mitral regurgitation and the differential effects of mitral valve repair and replacement surgeries. We have characterized the effects of alteration in ventricular geometry on exercise performance and ventricular filling in patients with congestive heart failure. Active collaborations exist with Dr. Ades studying the effects of resistance training in elderly patients with coronary disease and with Dr. LeWinter in his studies of left ventricular restoring forces.
Peter VanBuren, M.D.
Major Research Interests
Delineation of the role of sarcomeric proteins in the contractile deficit of human myocardial failure, applying human myocardial biopsy samples to an in vitro model of muscle contraction, and identifying key molecular defects in the contractile machinery. The knowledge be acquired should characterize promising targets for therapeutic modification of maladapted myocardial signaling pathways. Through novel therapy developed for identified targets improved survival in patients with heart failure may be achievable.
Matthew W. Watkins, M.D.
Dr. Watkins has participated in a gene therapy program at the University of Vermont and Fletcher Allen Health Care. He has played a significant role in the early clinical development of therapeutic angiogenesis for the treatment of advanced coronary artery disease. His research focuses on intracoronary delivery of genes with the use of a modified viral vector of the gene, FGF4 (fibroblast growth factor 4) that is designed to initiate an angiogenic response in chronically ischemic myocardium. The first intracoronary gene therapy treatment in the United States was performed at our institution with subsequent publication of the report of the initial phase one trial (AGENT I) demonstrating safety and preliminary efficacy of this treatment. A second multi-center investigation demonstrated a positive impact of FGF4 treatment on myocardial perfusion. An international phase three trial of therapeutic angiogenesis employing intracoronary delivery of FGF4 gene therapy is currently underway. Dr. Watkins is a member of the Steering Committee.
