Extension to Coronary Flow Reserve to Assess Hidden Risk: Focus on Women, Heart Failure, and Inflammation

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7. PROJECT SUMMARY/ABSTRACT: Dr. Viviany Taqueti is an early career cardiologist and physician-scientist at Brigham and Women's Hospital in Boston with a longstanding interest in endothelial and cardiomyocyte function and vascular inflammation. Her goal is to become a leading clinical investigator using functional imaging biomarkers to provide innovative mechanistic insights to clinical outcome studies at the intersection of inflammation and ischemia to inform future therapeutic trials. Her K23 award with requested administrative supplement present a comprehensive career development plan, including a detailed training proposal, structured mentorship, a well-developed advisory committee, and unequivocal institutional support, which together will provide Dr. Taqueti with the necessary support to transition successfully into an independent investigator. For over 2 decades, the annual cardiovascular disease (CVD) mortality rate has been higher for women as compared to men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Thus, even patients without significant obstructive CAD may be at high risk for adverse CVD events. The objective of the ongoing K23 research is to utilize an emerging, noninvasive imaging method of quantifying coronary blood flow to understand mechanisms of CVD outcomes in women and men across the anatomic CAD spectrum. Coronary flow reserve (CFR), calculated as the ratio of hyperemic to rest myocardial blood flow as quantified noninvasively by positron emission tomography (PET), is an integrated noninvasive measure of large and small vessel CAD and myocardial ischemia, and identifies patients at risk for CVD death independently of angiographic disease severity. This may be especially important for women, in who diffuse atherosclerosis and microvascular dysfunction likely contribute to CVD outcomes, especially heart failure, but are often undiagnosed. Our central hypothesis is that impaired CFR mediates excess CVD risk in women relative to men, and that this increased risk may be related to increased myocardial strain and increased inflammation. Dr. Taqueti is applying state of the art analyses to 2 complementary populations (CFR-Registry and CIRT-CFR, an ancillary study of the NHLBI sponsored multicenter Cardiovascular Inflammation Reduction Trial) to address the following specific aims: (1) To identify the relationship between sex, CFR and CAD plaque severity in symptomatic patients with suspected CAD [CFR Registry], (2) To define the extent to which CVD risk (especially heart failure events) is associated with impaired CFR in women relative to men, independently of CAD [CFR Registry], and (3) To define the relationship between CFR, myocardial strain, and inflammation in women and men with stable CAD [CIRT- CFR]. The results of this early career development award will (1) define the contribution of CFR to hidden CVD risk in women and men with varying levels of anatomic CAD, (2) clarify the role of microvascular dysfunction and inflammation in heart failure, (3) improve risk assessment to inform future preventive and therapeutic studies, and (4) serve as an ideal vehicle for Dr. Taqueti to transition to an independent investigator.