Effect of Varying Hemodynamic and Vascular Conditions on Fractional Flow Reserve: An In Vitro Study

BACKGROUND The aim of this study was to investigate the impact of varying hemodynamic conditions on fractional flow reserve (ratio of pressure distal [Pd] and proximal [Pa] to stenosis under hyperemia) in an in vitro setting. Failure to achieve maximal hyperemia and the choice of hyperemic agents may have differential effects on coronary hemodynamics and, consequently, on the determination of fractional flow reserve. METHODS AND RESULTS An in vitro flow system was developed to experimentally model the physiological coronary circulation as flow-dependent stenosis resistance in series with variable downstream resistance. Five idealized models with 30% to 70% diameter stenosis severity were fabricated using VeroClear rigid material in an Objet260 Connex printer. Mean aortic pressure was maintained at 7 levels (60-140 mm Hg) from hypotension to hypertension using a needle valve that mimicked adjustable microcirculatory resistance. A range of physiological flow rates was applied by a steady flow pump and titrated by a flow sensor. The pressure drop and the pressure ratio (Pd/Pa) were assessed for the 7 levels of aortic pressure and differing flow rates. The in vitro experimental data were coupled with pressure-flow relationships from clinical data for populations with and without myocardial infarction, respectively, to evaluate fractional flow reserve. The curve for pressure ratio and flow rate demonstrated a quadratic relationship with a decreasing slope. The absolute decrease in fractional flow reserve in the group without myocardial infarction (with myocardial infarction) was on the order of 0.03 (0.02), 0.05 (0.02), 0.07 (0.05), 0.17 (0.13) and 0.20 (0.24), respectively, for 30%, 40%, 50%, 60%, and 70% diameter stenosis, for an increase in aortic pressure from 60 to 140 mm Hg. CONCLUSIONS The fractional flow reserve value, an index of physiological stenosis significance, was observed to decrease with increasing aortic pressure for a given stenosis in this idealized in vitro experiment for vascular groups with and without myocardial infarction.