Less Invasive Detection and Treatment of Very Early Coronary Artery Disease in Patients With Diabetes Mellitus Using Regadenoson Stress Cardiac Magnetic Resonance Imaging

Type II Diabetes has become an epidemic in the United States. Cardiovascular disease is the most common cause of death in this population and is two to four fold higher than the general population. This increased risk is at least partially attributable to the high prevalence of the metabolic syndrome with its multiple coronary heart disease risk factors including central obesity, hypertension, glucose intolerance, chronic inflammation, and dyslipidemia. However, recent trials have demonstrated that traditional risk factors alone are not completely predictive of disease burden particularly early in the disease process prior to the development of flow-limiting coronary stenoses. Diagnosis and prevention of cardiovascular disease development has, thus, been elusive in this high risk population. It is not entirely clear which factors, known or novel, contribute the most in very early disease and which therapies may be most beneficial.

It has been suggested that microvascular dysfunction, a composite of endothelial dysfunction, abnormal blood cell rheology, and abnormal blood viscosity, precedes the development of overt coronary stenoses and contributes to increased cardiovascular risk very early in disease development. Microvascular reactivity is affected by many aspects of the metabolic syndrome. Commonly used tools may not be adequate to evaluate microvascular function in the heart at baseline or in response to therapy. Myocardial contrast echocardiography (MCE) and cardiac magnetic resonance imaging (CMR) provide noninvasive technology capable of directly measuring microvascular function within the heart. Our preliminary data with these modalities shows significantly reduced microvascular function in diabetes in the absence of distinct coronary stenoses.

Prior to development of stenoses in the coronary arteries, plaque accumulates via positive remodeling preserving the lumen. This can be detected invasively through the use of intravascular ultrasound (IVUS). Coronary CT is a potential noninvasive modality able to assess this early remodeling process, but it requires a substantial radiation dose and iodinated contrast dye. In addition, CT requires calcification to have occurred within the plaque, a finding believed to occur well into the life of the plaque. It is unclear how early plaque development is related to microvascular function and if stabilization or regression of plaque with available therapies improves microvascular function.

The overall hypothesis is that risk factors for the metabolic syndrome will predict invasive findings on IVUS and noninvasive findings on CMR perfusion imaging. Secondary objectives will include demonstrating the relative importance of individual risk factors early in disease, demonstrating the positive effects of aggressive risk factor modification on disease, demonstrating the relative importance of treatment of individual risk factors on disease progression or stabilization, and that invasive findings on IVUS will predict noninvasive findings with CMR. Such techniques may allow earlier noninvasive detection of disease as well as tailor treatment early in the disease process making prevention more cost effective.

The specific aims of this proposal are as follows: