Abstract

The importance of physiologic assessments in ischemic heart disease is well recognized. Coronary flow reserve (CFR) is a novel physiologic imaging biomarker that complements both anatomic and semiquantitative perfusion assessments of coronary artery disease (CAD) severity. Beyond this, assessment of CFR may provide clinical insights useful for refining diagnosis, prognosis, and eventually, management of patients along the full range of ischemic heart disease phenotypes, from multivessel obstructive CAD to diffuse coronary microvascular dysfunction. We begin by defining the concept of noninvasive CFR, specifically focusing on quantification of blood flow using PET, for which robust observational data exist. Next, we describe the continuum of cardiovascular risk by CFR values in patients across the anatomic spectrum of CAD, including those with diabetes, chronic kidney disease, and nonobstructive CAD and coronary microvascular dysfunction. Finally, we summarize the impact of CFR on prognosis, with a focus on future directions for management strategies and potential novel therapies, particularly in patients with very low CFR and less obstructive CAD. This latter phenotype may provide a critical link to understanding hidden biological risk of ischemic heart disease in vulnerable populations, including women and patients with heart failure with preserved ejection fraction, metabolic syndrome, cardio-oncologic complications, and inflammatory-related disease.

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