Model‐based analysis of the sensitivities and diagnostic implications of FFR and CFR under various pathological conditions

Although fractional flow reserve (FFR) and coronary flow reserve (CFR) are both frequently used to assess the functional severity of coronary artery stenosis, discordant results of diagnosis between FFR and CFR in some patient cohorts have been reported. In the present study, a computational model was employed to quantify the impacts of various pathophysiological factors on FFR and CFR. In addition, a hyperemic myocardial ischemic index (HMIx) was proposed as a reference for comparing the diagnostic performances of FFR and CFR. Obtained results showed that CFR was more susceptible than FFR to the influence of many pathophysiological factors unrelated to coronary artery stenosis. In particular, the numerical study proved that increasing hyperemic coronary microvascular resistance significantly elevated FFR while reducing CFR despite fixed severity of coronary artery stenosis, whereas introducing aortic valve disease only caused a significant decrease in CFR with little influence on FFR. These results provided theoretical evidence for explaining some clinical observations, such as the increased risk of discordant diagnostic results between FFR and CFR in patients with increased hyperemic microvascular resistance, and significant increase in CFR after surgical relief of severe aortic valve disease. When evaluated with respect to the predictive value for hyperemic myocardial ischemia, the performance of FFR was found to be considerably compromised in the presence of severe coronary vasodilation dysfunction or aortic valve disease, whereas the relationship between CFR and HMIx remained relatively stable, suggesting that CFR may be a more reliable indicator of myocardial ischemia under complex pathophysiological conditions.