Comparison of fractional flow reserve, instantaneous wave-free ratio and a novel technique for assessing coronary arteries with serial lesions

Aims: Physiological indices such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and resting distal coronary to aortic pressure (Pd/Pa) are increasingly used to guide revascularisation. However, reliable assessment of individual stenoses in serial coronary disease remains an unmet need. This study aimed to compare conventional pressure-based indices, a reference Doppler-based resistance index (hyperaemic stenosis resistance [hSR]) and a recently described mathematical correction model to predict the contribution of individual stenoses in serial disease. 

Methods and results: Resting and hyperaemic pressure wire pullbacks were performed in 54 patients with serial disease. For each stenosis, FFR, iFR, and Pd/Pa were measured by the translesional gradient in each index and the predicted FFR (FFR_pred) derived mathematically from hyperaemic pullback data. “True” stenosis significance by each index was assessed following PCI of the accompanying stenosis or measurements made in a large disease-free branch. In 27 patients, Doppler average peak flow velocity (APV) was also measured to calculate hSR (hSR=∆P/APV, where ∆P=translesional pressure gradient). FFR underestimated individual stenosis severity, inversely proportional to cumulative FFR (r=0.5, p<0.001). Mean errors for FFR, iFR and Pd/Pa were 33%, 20% and 24%, respectively, and 14% for FFR_pred (p<0.001). Stenosis misclassification rates based on FFR 0.80, iFR 0.89 and Pd/Pa 0.91 thresholds were not significantly different (17%, 24% and 20%, respectively) but were higher than FFR_pred (11%, p<0.001). Apparent and true hSR correlated strongly (r=0.87, p<0.001, mean error 0.19±0.3), with only 7% of stenoses misclassified. 

Conclusions: Individual stenosis severity is significantly underestimated in the presence of serial disease, using both hyperaemic and resting pressure-based indices. hSR is less prone to error but challenges in optimising Doppler signals limit clinical utility. A mathematical correction model, using data from hyperaemic pressure wire pullback, produces similar accuracy to hSR and is superior to conventional pressure-based indices.