Coronary Flow Reserve in Adults: Pathophysiology, Assessment Modalities, Clinical Applications, and Prognostic Significance

Coronary flow reserve (CFR) is a fundamental physiological index defined as the ratio of maximal coronary blood flow during hyperemia to resting flow. It provides an integrated assessment of the entire coronary circulation, from epicardial arteries to the microvasculature. Non-invasive assessment, particularly with transthoracic Doppler echocardiography (TTDE), is valuable in clinical practice for evaluating the functional impact of moderate obstructive lesions and determining the status of coronary microcirculation. Impairment of coronary microcirculation, detected by reduced CFR, is present in diverse conditions such as Tako-Tsubo cardiomyopathy, cardiac syndrome X, hypertension, and slow coronary flow. CFR also serves as a non-invasive tool to examine the effects of various interventions. CFR can be assessed invasively using Doppler guidewire or thermodilution techniques and non-invasively using transthoracic Doppler echocardiography, PET, CMR, CT perfusion, and dynamic SPECT. Lower CFR is observed with advancing age, in females, and in individuals of African descent. An impaired CFR is a powerful, independent predictor of major adverse cardiovascular events (MACEs) across a wide spectrum of diseases, including stable obstructive coronary artery disease (CAD), ischemic syndromes with no obstructive coronary arteries (INOCAs), heart failure, cardiomyopathies, and systemic diseases like diabetes and chronic kidney disease. Beyond risk stratification, CFR is used to guide therapeutic decisions, including revascularization strategies and tailoring of pharmacological interventions. The integration of CFR assessment into clinical practice, supported by recent guideline recommendations, represents a shift towards personalized, physiology-based cardiovascular care.