Beyond stenosis with fractional flow reserve via computed tomography and advanced plaque analyses for the diagnosis of lesion-specific ischemia

In the treatment of stable coronary artery disease (CAD), the determination of stenosis severity by invasive coronary angiography (ICA) is a critical procedure, and for borderline lesions, the detection of ischemia through invasive fractional flow reserve (FFR) is the gold standard. With advances in computational fluid dynamics, FFR can now be calculated noninvasively using anatomic data from coronary computed tomographic angiography (CCTA). This technique is known as FFR_CT. The purpose of this review is to summarize the science of FFR_CT, describe its diagnostic accuracy, discuss its clinical and economic impact, and elucidate factors beyond stenosis severity that may mechanistically relate to lesion-specific ischemia. These factors include adverse atherosclerotic plaque characteristics such as positive remodelling, low-attenuation plaque, and spotty calcification, as well as aggregate plaque volume. These factors can be appreciated noninvasively by CCTA but not by ICA. The diagnostic accuracy of FFR_CT, compared with the gold standard of FFR, has been validated in 3 prospective multicentre blinded core laboratory–controlled trials, and as a result FFR_CT has been approved by the US Food and Drug Administration for clinical use. FFR_CT has also been shown in a clinical utility trial to better identify patients without obstructive CAD when compared with standard noninvasive assessment of stable CAD, thereby avoiding unnecessary angiograms. In addition, the use of FFR_CT has been shown to allow for a significant cost savings compared with traditional care. It is therefore important for cardiologists to appreciate the value of this important new methodology.