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Research Studies
Cardiovascular/Vascular
| Detection and Assessment of Free Fatty Acid Utilization by Cardiac Muscle in Patients with Lipoprotein Lipase Deficiency using PET (5214) |
We plan to study myocardial blood flow, oxygenation and free fatty acid, and glucose uptake by the cardiac muscle using Positron Emission Tomography (PET).
Fatty Acids (FA) are an important fuel source for heart and skeletal muscle, providing over 70% of the energy needs for cardiac function. FA is delivered to cardiac myocytes in three ways:
1) FA are derived from the hydrolysis of triglyceride (TG) stored in adipose tissue via hormone-sensitive lipase and circulate in the blood with albumin;
2) FA are produced from intracellular hydrolysis of TG in the core of internalized lipoproteins;
3) FA are also generated in the local capillary bed by lipoprotein lipase (LPL)-mediated hydrolysis of TG in circulating chylomicrons and very low-density lipoproteins (VLDL).
The purpose of this investigation is to determine how the hearts of patients with LPL deficiency obtain fatty acids or glucose as a source of energy. In addition, the myocardial blood flow and oxygenation of the heart of individuals with LPL deficiency will be evaluated.
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| Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease (SPARC) () |
SPARC, including its Pilot CT angiographic study, is a prospective, open-label, multicenter, sequentially sampled, observational registry to define the clinical value of stress perfusion (stress SPECT, stress PET), noninvasive angiography (CTA) and combined perfusion-anatomy (PET/CT) studies in patients with known or suspected CAD with respect to post-test resource utilization and prediction of cardiac death and non-fatal myocardial infarction.
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| Novel Radionuclide Imaging Approaches for the Early Diagnosis of Pulmonary Arterial Hypertension and the Detection of its Later Sequelae () |
Pulmonary artery hypertension as a familial disease, associated with scleroderma, or congenital heart disease, it is an uncommon disorder but highly lethal. Frequently the diagnosis is not made until the patient develops symptoms associated with hemodynamic compromise that is a late sequela of the disease. The cause of death in these patients is most likely due to right ventricle (RV) failure.
It would be clinically important to identify these patients earlier in the course of the disease. This study is designed to study subjects’ right ventricle functions (blood flow, substrate metabolism, etc.) with a non-invasive imaging modality, Positron Emission Tomography (PET). The data obtained from this study may prove valuable in early diagnosis, determinant of prognosis, selection of patients for therapy, and for evaluating new drugs.
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| FDG Uptake on PET is a Marker for Internal Carotid and Aortic Plaque Instability
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Specific Aims: To test the hypothesis that F-18 FDG uptake is a marker of plaque instability in patients with documented plaque in the internal carotid arteries and/or in the aorta.
Subject Population: This study will enroll up to 30 patients with a lower age cut off of 40 years. Patients with atherosclerosis, including those with type II diabetes and vascular disease, will be referred for PET scanning from the vascular and cardiac (TEE) ultrasound laboratories. All patients will have laboratory evaluation of C-reactive protein at the time of enrollment. Positron emission tomography will be performed on all patients from the base of the skull to the proximal thighs after injection of F-18 fluorodeoxyglucose. Uptake of tracer will be localized and scored by extent and intensity.
Data Analysis: All patients will be followed for events including CNS events (stroke, TIA) as well as myocardial infarction since vascular inflammation may be a widespread process. Levels of CRP will also be correlated with events as well as with scan uptake. F-18 FDG PET scan results will be both dichotomized as +/- and considered as a continuous variable based on quantitative uptake.
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| Phase III, Randomized, Double Blind Study of Intravenous CVT-3146 vs. Adenosine in Patients Undergoing Stress Myocardial Perfusion Imaging () |
CVT-3146 is a novel A2A adenosine vasodilator receptor agonist that has been found to cause selective coronary vasodilatation in isolated heart preparations and in animal models. CVT3146 has begun clinical investigation for use as a pharmacologic stress agent during radionuclide myocardial perfusion imaging.
In 2001, almost 3 million or 42% of patients who underwent stress myocardial perfusion imaging were tested with the pharmacological agents adenosine and dipyridamole (both are vasodilators), or the inotropic agent dobutamine. The most frequent reasons cited for using pharmacological stress in place of exercise are the inability of the patient to exercise sufficiently on the treadmill due to deconditioning, or the complications associated with withholding certain medications during exercise.
Because adenosine activates all four known adenosine receptors (A1, A2a, A2b, and A3, A4) it is responsible for several associated undesirable side effects. Since CVT3146 causes a potent and selective coronary vasodilatation, with a rapid onset and short duration of action it suggests it would be a useful agent during radionuclide myocardial perfusion imaging. In addition since CVT3146 is a selective A2a agent it is anticipated to have less undesirable side effects such as atrioventricular block, which is a results of stimulation of the A1 receptors, and broncoconstriction, which is due to stimulation of the A3 adenosine receptors.
The primary objective of this study is to demonstrate the strength of agreement between CVT-3146 and adenosine images is not inferior to two sequential adenosine images.
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Patients
