The interest in resting physiology to estimate the functional significance of an epicardial stenosis was first explored by Grüntzig [
5], and has recently been revisited. Compared to the FFR reference metric, alternative resting indices achieve a diagnostic accuracy of approximately 80% (80.4 and 82.5% from the RESOLVE and ADVISE-II analyses respectively) when compared to FFR [
37,
38]. This interest has been prompted by the desire to avoid adenosine hyperaemia due to short-lived patient side-effects including flushing and dyspnoea, and the cost and limited availability of adenosine in some parts of the world. ‘Whole-cycle resting Pd/Pa′ is the distal coronary pressure indexed to aortic pressure without the induction of hyperaemia, whereas iFR
® is defined as the pressure ratio at rest during a time interval starting 25% into diastole and ending 5 ms before onset of systole. iFR
® is calculated using proprietary software, whereas resting Pd/Pa is available generically using any FFR system. For an FFR ischaemic threshold of ≤0.75, whole-cycle resting Pd/Pa cut-offs of ≤0.85 to ≥0.93 have been proposed (with a positive predictive value of 95% and negative predictive value of 95.7% respectively) [
39]. iFR
® was initially proposed by the ADVISE investigators as an adenosine-free test with a threshold of 0.83 being equivalent to the clinical FFR threshold of 0.80 [
37,
40], however, research by the VERIFY investigators confirmed that iFR
® is lowered significantly when measured during intravenous adenosine infusion [
41]. This threshold has since been revised to 0.89 with a diagnostic accuracy of around 82.5% [
38]. Using a hybrid algorithm which incorporates hyperaemic FFR measurements, patients whose iFR
® falls in the 0.86–0.93 range receive adjunctive adenosine and undergo full FFR assessment due to diagnostic uncertainty in the so-called ‘adenosine zone’. This accounts for up to 35–45% of cases undergoing assessment but results in greater diagnostic accuracy versus FFR [
42‐
44]. Clinical trials designed to assess health outcomes with iFR versus FFR-guided management are ongoing [
45] (Fig.
4).