The fractional flow reserve grey zone: a blueprint for the future of coronary revascularisation

Forty years since Andreas Gruentzig performed the first percutaneous coronary intervention (PCI), the rationale for revascularisation in stable coronary artery disease (CAD) continues to evolve. The cardiology community has shifted from revascularisation of all anatomically obstructive lesions towards deferring and medically managing stenoses with preserved flow as measured by fractional flow reserve (FFR). Clinical trials have established the role of FFR in contemporary therapeutic decision making, with FFR-guided revascularisation associated with a reduction in the incidence of myocardial infarction, improved angina relief compared with optimal medical therapy (OMT) and reduced healthcare costs.1 2 ​Decision making in modern medicine is often driven by binary cut-offs, a strategy that has both strengths and limitations. On one hand, a binary cut-off can facilitate decision making and ease of interpretation, and therefore encourages the use of intracoronary physiology in clinical practice. In contrast, the use of a rigid cut-off does not account for the biological and measurement variability of FFR, thereby introducing a degree of inaccuracy around the diagnostic threshold. Initially an FFR value of 99% positive predictive value for inducible myocardial ischaemia across multiple non-invasive modalities.3 4 Given the observation that in a small proportion of lesions an FFR between 0.75 and 0.80 was associated with flow-limiting stenosis, the FFR threshold to guide revascularisation in the FAME trials was increased to 0.80 to improve its sensitivity in detecting ischaemia at the cost of specificity.2 Accordingly, an FFR grey zone for values between 0.75 and 0.80 was recommended in which decision making should be based on clinical judgement and the presence of additional information.1 Yet using binary cut-off values in interpreting FFR goes beyond diagnostic accuracy and has implications for its prognostic value. Previous …