## 3 Results  
_Model FFR during the cardiac cycle:_ Time-dependent FFR in the three major coronary arteries (LAD, LCX, and RCA) under predefined large vessel stenosis and microvascular disease is illustrated in Figure 2. The control simulation (Figure 2, top row) devoid of stenosis or microvascular disease shows that FFR is high (more than 0.8) during the complete cardiac cycle in all three vessels. Due to flow distribution from the aorta to the smaller coronary network, the time dependent FFR was seen to reduce during systole. The time dependent FFR when either LAD, LCX, or RCA were focally stenosed by 90% (\(\alpha=0.9\)) is shown in Figure 2, middle row. When there was a full vessel length stenosis the FFR values reduced to 0.56 for the LAD, 0.52 for the LCX, and 0.5 for the RCA. Whereas the overall FFR was observed to reduce significantly in all three simulations, large vessel stenosis led to minimal FFR during the cardiac cycle's diastole. Simulated microvascular disease, simulated by augmenting all terminal impedances by 50% (\(\varepsilon=2.55\), a reduction of \(\varepsilon\) increases impedance, Z), led to amplifying the difference between the aortic and respective distal pressures and gave a minimal FFR estimate during the systole (Figure 2, bottom row). When microvascular disease was simulated, the maximum time dependent FFR value was calculated to be 1 and minimum to be 0.7 in all three blood vessels. The coronary flow in the control coronary model (Figure 3, top row) and its reduction due to focal stenosis (Figure 3, middle row) and microvascular disease (Figure 3, bottom row) was computed. Relative to the control case (Figure 3, top row), focal stenosis (Figure 3, second row) restricted flow significantly in all three blood vessels. When microvascular disease was implemented, the maximum flow and overall flow in the network decreased. Further, the impact of individual artery resistances, inertances, and compliances were blunted as reflected in the flow profiles (Figure 3, bottom row). Figure 2: Pressure profiles and FFR in the LAD (column **A**), LCX (column **B**), and RCA (column **C**). In all columns, top row shows non-stensored model behavior, second row shows the result of focal stenosis (\(\alpha=90\%\)), and third row shows the result of downstream microvascular disease in the absence of focal stenosis (\(\alpha=100\%\); \(\epsilon=2.33\)). In all panels, black lines and axis represent aortic pressure (proximal pressure) while red lines and axis represent the pressure of vessel of interest (distal pressure). Time dependent FFR is shown as orange dashed lines. _Focal and diffuse stenosis interplay:_ The dependence of average flow (flow), maximum flow, and FFR on simultaneous presence of reduced vessel diameters (focal stenosis) and diffuse stenosis (reduction of diameters along a predefined length) were quantified (Figure 4). In all vessels, the detrimental effects of stenosis on flow (Figure 4, top row) and maximum flow (Figure 4, middle row) were impacted by the severity of focal stenosis (horizontal axis) to a greater extent than the severity of diffuse stenosis (vertical axis). Progressive focal stenosis alone was found to minimally impact the estimated FFR (Figure 4, bottom row) due to the model formulation (see above). As such, a reduction of FFR was observed when the stenosis was diffuse to a certain extent. Conversely, diffuse stenosis in the absence of focal stenosis (vertical axis in Figure 4) also did not reduce FFR. Progressive focal stenosis in the RCA caused the largest reduction in FFR (Figure 4, third row) as compared to focal stenosis in the LAD and LCX in the presented model. In the presented model, the RCA was more susceptible to FFR reduction due to stenosis in comparison to the LAD and LCX. Simultaneous presence of focal and diffuse stenosis caused the most severe reduction of FFR in the RCA, followed by the LAD and LCX.