Background Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease.

Methods and results We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r²=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r²=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR.

Conclusions Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.