The study of the hemodynamic relevance of coronary stenoses is a well-validated method to identify coronary lesions to be treated. A number of studies show that FFR-guided PCI is superior to angiography guided PCI2-4. The achievement of maximal hyperemia is a prerequisite for FFR measurements. Hyperemia is usually achieved with the intravenous or intracoronary infusion of adenosine, which requires time and is potentially associated with discomfort for the patient. To avoid this, resting indexes have been developed. The instantaneous flow reserve (iFr) was the first of these indexes, and two large studies have shown that this parameter is non-inferior to FFR in terms of patient prognosis5. More recently, a number of other parameters have been developed, among which the RFR (resting flow ratio), which can be measured with the same intracoronary wire as the FFR and therefore requires no additional procedures. Studies show that these methods are equivalent6. The advantage of these resting indexes (which are all included in the most recent AHA/ACC guidelines7, 8), is that they do not require hyperemia. This might represent a particular advantage in the setting of tandem stenoses or diffuse disease. Since hyperemic flow in a vessel is limited by each one of the stenoses present in that vessel, each individual stenosis limits the capacity of FFR to assess the hemodynamic relevance of the other ones. In other words, invasive measurements of coronary hemodynamics using FFR in the setting of diffuse or tandem lesions are complicated by the fact that maximal hyperemia cannot be achieved, which limits the capacity of FFR to assess the hemodynamic relevance of individual focal stenoses. In this setting, the usual binary system (FFR \< or \> 0.80) cannot be easily applied.

This limitation is independent of the sequence of the stenoses: proximal lesions limit the reliability of FFR measurements in distal stenoses and vice versa (as long as no significant side branches are present between the two lesions). Since hyperemic flow declines significantly as soon as a 50% reduction in lumen diameter is present, even apparently non-relevant lesions may compromise any assessment based on hyperemia. This phenomenon, called hemodynamic interdependence of stenoses under conditions of hyperemia represents a significant limitation that applies to FFR but not to hyperemia-free indexes.

In order to address this issue in routine practice, FFR is measured first, then a pullback is performed and the lesion/segment where the pullback identifies the highest gradient is treated first. The removal of this stenosis increases maximal achievable hyperemic flow, thus increasing the significance of the remaining lesions. FFR is then measured again to test the hemodynamic significance of the other stenoses at a higher level of hyperemia. The capacity of FFR to predict whether removal of the first stenosis will be associated with the normalization of FFR is very limited, which requires that FFR be measured multiple times, prolonging the procedure and increasing the discomfort for the patient.

When studying coronary stenoses, the advantage of resting hemodynamic indexes is that non-critical stenoses (ie below 90%) do not modify resting blood flow. Because resting flow is more constant, and the effect of PCI is minimal, resting pressure changes measured across sequential lesions are likely to be more predictable.The hypothesis of the study is that, as compared to FFR, RFR will provide a better estimate of post-PCI hemodynamic outcomes.