The purpose of this proposal is to promote scientific development and investigative skills of the candidate in order that she may become an independent clinical investigator. The noninvasive cardiovascular imaging center at the Brigham and Women's Hospital provides the Ideal setting in which the candidate will study the prognostic value of coronary microvascular function, while enrolled in a Masters degree in Public Health at the Harvard School of Public Health. Through the collaboration with the clinical mentor, and highly experienced scientific advisors, the candidate will obtain a foundation for the development of an independent academic career. The link between myocardial ischemia, epicardlal coronary artery disease (CAD) and survival Is well established. More recently, coronary microvascular dysfunction has been reported in several clinical syndromes such as hypertensive heart disease, cardiomyopathy and syndrome X, In subjects without obstructive epicardlal CAD. Preliminary evidence suggests that microvascular dysfunction is associated with worse outcomes. Until recently, evaluation of coronary microvascular function has been impeded by methodological limitations, and hence, its nature and mechanisms remain speculative. Positron emission tomography (PET) represents an extremely powerful tool to assess coronary microvascular function. The central goal of this study is to determine the prognostic value of coronary microvascular function using Rubldlum-82 PET. The candidate has demonstrated the prognostic value of relative Rubldium-82 PET, reflecting severity of epicardlal CAD.
In specific Aims 1 -3, the candidate will study the value of coronary microvascular function to predict major adverse cardiac events of sudden death, risk of left ventricular remodeling/heart failure, and risks from progression to obstructive epicardlal CAD. We anticipate that the proposed studies outlined here will provide important mechanistic links between coronary microvascular dysfunction and cardiac events. The results of these studies will serve as a foundation to design future studies of specific therapies directed at improving coronary microvascular function and clinical outcomes.

Public Health Relevance

The big coronary arteries supplying blood to the heart course on the surface and are visible by dye injection (angiography), but the vessels entering the heart muscle are very small and not seen on angiography. These microvessels play a major role in blood flow to the heart, especially during activity. The purpose of this study is to find out If microcirculatory abnormalities can predict risk of future adverse outcomes from heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (M1))
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Roltsch, Mark
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Brigham and Women's Hospital
United States
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