Flow restoration post revascularization predicted by stenosis indexes: sensitivity to hemodynamic variability.

The expected blood flow improvement following a coronary intervention is inversely related to the stenotic-to-normal flow ratio Qs/Qn. Since Qn cannot be measured prior to intervention, treatment decisions rely on stenosis-severity indexes, e.g., area stenosis (%AS), hyperemic stenosis resistance (HSR), and fractional flow reserve (FFR), where treatment cut-off levels have been established for each index based on presence of inducible ischemia. Here, we studied the dependence of these indexes-predicted Qs/Qn under physiological perturbations of stenosis features and of hemodynamic and mechanical conditions. Dynamic coronary flow was simulated based on measured coronary morphometric data and a physics-based computational model. Simulations were used to evaluate the relationship between each index level and Qs/Qn. Under each perturbation, an independence measure (IM) was calculated for each index based on the relative change in Qs/Qn associated with each perturbation. The results show that while %AS prediction of Qs/Qn is largely independent (IM > 90%) of physiological changes in heart rate, venous pressure, and lesion length and location on the epicardial tree, HSR is also independent of changes in left ventricle pressure. FFR-predicted Qs/Qn is also independent of changes in aortic pressure, blood hematocrit, and stenotic vessel stiffness. Nevertheless, independence of all indexes is substantially compromised (IM < 70%) under changes in vasculature stiffness. Specifically, a physiological stiffening elevates Qs/Qn value by 21% at the FFR cut-off value (0.75). These findings suggest that the current FFR cut-off value for treatment of stenotic lesions overestimates the benefit of coronary intervention in patients with a stiffer coronary vasculature (e.g., diabetics, hypertensives).