Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study

Figure 1. Schematic description of 0-1-D multiscale modeling of the coronary circulation coupled to the global cardiovascular system. Note that coronary branch arteries in the RCA and LCx territories were modeled but are not presented in the figure in order to save space. A stenosis was introduced in the middle segment of LAD, with blood pressure immediately distal to it (Pd) being monitored along with blood pressure at the aortic root (Pa) for the purpose of calculating iFR or FFR. More details of model development, parameter assignment, and numerical methods have been described in our previous studies [21, 22]. Abbreviations: LM, left main artery; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; RCA, right coronary artery. Notations of main parameters: L, vascular inductance; R, vascular resistance; C, vascular compliance; E, elastance of cardiac chamber; Pit, intrathoracic pressure; Pim, intramyocardial tissue pressure.

Figure 2. Model-simulated changes in iFR/FFR with the increase in the severity (i.e., the diameter stenosis rate is increased from 0% to 70% at an interval of 10%) of a stenosis present in mid-LAD under the control resting/hyperemic condition. When FFR is at the cutoff value (i.e., 0.8), the corresponding stenosis rate (SR) is 51% and iFR is 0.913.

Figure 3. Model-simulated aortic and poststenosis coronary arterial pressure waves (a∼c), wave intensity in mid-LAD (d∼f), and poststenosis coronary microvascular resistance (g∼i) during iFR measurement under the control and two altered physiological conditions (one with a 67% increase in HR and the other with a 200% increase in aPWV). The wave-free period (WFP) during a cardiac cycle is highlighted by the gray shadow. The stenosis was present in mid-LAD, with the stenosis rate being fixed at 50% in all the simulations.

Figure 4. Percentage changes of iFR and FFR relative to their reference values upon the variations of each model parameter. The variations of all parameters except for EOAdia and EOAsys are expressed in normalized form relative to their reference values to facilitate the comparisons of the effects on iFR/FFR among different parameters. The stenosis is present in mid-LAD with its stenosis rate being set at 50% and 70%, respectively, and the corresponding reference values (computed with all model parameters being fixed at their reference states) of iFR/FFR are 0.920/0.813 and 0.677/0.534, respectively. (a) EOAdia. (b) EOAsys. (c) Elva. (d) Elvb. (e) HR. (f) aPWV. (g) Rsys. (h) Rcmv. Notations: EOAdia/EOAsys, effective orifice area of aortic valve during diastole/systole (an increase in EOAdia represents an increase in the severity of aortic valve regurgitation, whereas a decrease in EOAsys represents an increase in the severity of aortic valve stenosis); Elva/Elvb, peak systolic elastance/baseline diastolic elastance of the left ventricle; HR, heart rate; aPWV, aortic pulse wave velocity; Rsys, total systemic vascular resistance; Rcmv, total coronary microvascular resistance.

Figure 5. Comparisons of model-simulated aortic pressure wave and coronary arterial pressure wave distal to a 50% stenosis in mid-LAD and iFR/FFR (a∼d), flow wave in mid-LAD (e∼h), and poststenosis coronary microvascular resistance (i∼l) under control resting/hyperemic condition with those in the presence of severe AS (EOAsys = 1.0 cm2) or increased coronary microvascular resistance (increased by 120% relative to the reference value).

Figure 6. Effects of different combinations of AS (with its severity being controlled by the value of EOAsys) and increased coronary microvascular resistance (Rcmv, herein normalized by its reference normal value) on (a) iFR and (b) FFR. Increasing the severity of AS leads to a marked decrease in iFR and moderate increase in FFR, whereas increasing Rcmv causes a progressive increase in both iFR and FFR. As a consequence, increasing Rcmv counteracts or even reverses the decrease in iFR while augments the increase in FFR caused by AS. Note that the coronary stenosis is present in mid-LAD with its severity being fixed at 50% in all the simulations and that the values of iFR and FFR highlighted by the filled circles indicate their reference values computed under the condition that only the 50% coronary stenosis is present while AS and increased Rcmv are absent.