Fractional flow reserve (FFR) measurement under hyperemic conditions has been the gold standard for invasively determining the physiologic significance of coronary artery disease. Recently, two large-scale randomized controlled trials using a nonhyperemic resting measurement for physiological assessment of moderate coronary stenoses, the instantaneous wave-free ratio (iFR), reported noninferiority for major adverse cardiovascular events (MACE) comparing iFR to FFR at one-year follow-up. These studies demonstrated a statistically significant reduction in patient discomfort and in cost by avoiding adenosine. However, iFR has a number of inherent limitations including sensitive automated landmarking of components of the pressure waveform and the assumption that maximal flow and minimal resistance during resting conditions occur during a precise period within diastole, which previous evidence contests.

The VALIDATE-RFR aimed to validate a novel hyperemia-free resting measure of pressure at the point of absolute lowest resting diastolic pressure (Pd) to aortic pressure (Pa) ratio (Pd/Pa) during the cardiac cycle, the resting full-cycle ratio (RFR). The RFR represents the maximal relative pressure difference in the cardiac cycle completely independent of the ECG and irrespective of systole or diastole, thus being an unbiased physiological assessment of coronary artery stenosis. RFR was shown to be diagnostically equivalent to iFR but unbiased in its ability to detect the lowest Pd/Pa during the full cardiac cycle, thus unmasking physiologically significant coronary stenoses that can be missed by assessment focused on specific segments of the cardiac cycle.

TAKE HOME MESSAGE: The resting full-cycle ratio (RFR) may be used as an alternative to resting distal coronary pressure to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) as a nonhyperemic index to assess coronary artery stenosis severity. Unlike iFR, RFR is not limited by sensitive landmarking of components of the pressure waveform or specific to the wave-free period, and thus may have greater clinical utility as a result of its versatility. Nonetheless, RFR is diagnostically equivalent to iFR, justifying its extension to all guidelines and clinical recommendations for iFR.