Fractional flow reserve-guided percutaneous coronary intervention: does coronary pressure never lie?

Fractional flow reserve (FFR)-guided coronary revascularization is associated with an unequivocal clinical benefit compared with angiographic guidance. However, the well-documented clinical merit of FFR-guided revascularization has resulted in several misunderstandings as to its diagnostic characteristics. Moreover, it has led to the use of FFR as a gold-standard reference test for the identification of stenosis-related inducible myocardial ischemia. Frequently overlooked is the fact that FFR was originally validated against noninvasive stress-testing to document its ability to identify ischemia-generating stenoses, as well as its optimal cut-off value to do so, which illustrates the paradox of using FFR as a gold-standard reference for this purpose. The diagnostic characteristics of FFR are more complex than is widely understood, and its conceptual validity is based on multiple assumptions that are not considered in clinical practice. In contrast, the validity of FFR as a clinical tool is based on empirical evidence derived from multiple large-scale randomized controlled trials. It is, therefore, of great importance to understand the fundamental physiological basis of FFR, and to be aware of the underlying assumptions and their implications, for appropriate application and interpretation of FFR on an individual basis. This review aims to elucidate the assumptions that underlie the concept of FFR, to provide insight into their consequences for daily practice, and to highlight the practical methodology that is critical for its interpretation in clinical practice.