Instantaneous wave-free ratio to guide coronary revascularisation: physiological framework, validation and differences from fractional flow reserve

Determining the optimal treatment strategy for revascularisation of coronary artery stenosis involves the use of fractional flow reserve (FFR). To improve the low clinical uptake of physiological lesion assessment to guide revascularisation, the instantaneous wave-free period (iFR) was proposed as a simpler alternative to FFR that does not require adenosine administration. iFR is calculated as the ratio of blood pressure distal and proximal to a coronary artery stenosis during the diastolic wave-free period. The wave-free period is a part of the cardiac cycle where generation of new pressure wavefronts does not occur and resting microvascular resistance is relatively minimised. iFR indicates the haemodynamic severity of a stenosis, by assessing the extent to which the epicardial stenosis depletes the microcirculatory, autoregulatory reserve. The introduction of iFR and the potential to assess haemodynamic stenosis severity without the need for administration of potent vasodilators such as adenosine sparked an interesting debate about the fundamentals of human coronary physiology. The outcomes of two randomised clinical trials investigating iFR are pending. These studies are designed to evaluate whether iFR-guided revascularisation is non-inferior to an FFR-guided approach. The purpose of this review article is to discuss the physiological concepts underlying iFR, examine the existing validation studies and discuss the advantages and disadvantages of iFR as compared to FFR.