A lthough atherosclerotic lesion burden and severity is a continuum, the decision to revascularize a patient or not is a dichotomous one. Therefore, like other quantitative cutoffs used in stress testing, angiography, or intravascular ultrasound imaging, thresholds of fractional flow reserve (FFR) have been sought and validated (1). Initially, an FFR value of 0.75 was established as the best threshold to discern an ischemia-provoking lesion. Subsequently, recognition of some variability in FFR measurement, both biological and technical, occurred, resulting in the description of a “gray zone” between 0.75 and 0.80, where other clinical and angiographic factors can inform revascularization decisions (2). Even though large studies, such as the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) and FAME II studies established a binary FFR cutoff of 0.80 as the threshold for clinical decision making, understanding and correcting the sources of variability in pressure measurements is critical for optimal FFR assessment. FFR measurement has a lower coefficient of variation than other physiological tests such as coronary flow reserve. Yet, some intrinsic FFR variability related to dynamic changes in preload, afterload, coronary flow, and myocardial contractility and resistance may occur. Another issue that can impact
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