## 4 Discussion  
A coupled FSI model is used to simulate the cardiac cycle of virtual patients with hypertrophic and dilated cardiomyopathy. The simulations are performed using the PAKBio FE solver while the parametric LV models are generated using the in-house CAD Solid and Field interface software. A simple parametric \"virtual patient\" model can be easily adapted to patient-specific parameters and run for a range of clinical metrics detected using MRI and catheterization. The presented approach using variations in LV geometry and simulations, including the effects of various parameters on the PV diagrams, is directly linked to the drug effects on cardiac function obtained using the MUSICO platform. The PV diagrams, velocity, and pressure fields are calculated for different Ca2+ concentrations, wall stiffnesses, and inlet and outlet velocities. A quantitative evaluation of the effects of various medicines (digoxin, dATP, disopyramide, and mavacamten) on the cardiac output, encompassing both systolic and diastolic pressures, as well as the ejection fraction, is also provided by the FE simulations. As can be seen from Figure 4a, the mitral valve pressure reaches its greatest value at t = 0.4 s, during the first 0.5 s of the cycle, as fluid is pumped into the ventricle and its volume rises. When the first part of the cardiac cycle finishes and the mitral valve closes, the ventricle contracts (contraction is shown towards the end of the systole at 0.9 s in Figure 4a), and fluid flows out of the aortic valve. Regarding the velocity field, in Figure 4b, during diastole, there is a noticeable peak inside the input branch (mitral valve). During systole, the peak is noticeable at the output branch (aortic valve). When the wall contracts and fluid starts to flow out, the bottom part of the wall deforms the most. The velocities diminish over the remaining time as the solid wall progressively reverts to its initial state. As can be seen from Figures 6a and 7a, the triangular calcium concentration has the slowest decrease rate. Then, the LV muscle is activated for a prolonged period and, as a result, the surface bonded by the PV curve is large and therefore the amount of blood ejected from the LV is high. The parabolic calcium concentration function has the earliest rise of calcium and, since the muscles are activated prematurely, the isovolumetric contraction occurs earlier with respect to the other two cases. With the steep concentration function,  
Figure 8: Dependence of the ejection fraction in DCM and HCM models on (**a**) inlet velocity, (**b**) outlet velocity, and (**c**) wall elasticity (stiffness). Percentages are with respect to the nominal (referent) conditions, (**d**) calcium concentration functions for different drugs, and (**e**) corresponding PV diagrams. less blood is ejected than with the triangular function, and the muscle is activated later than with the parabolic function. In the case of a shifted and wider parabolic Ca2+ concentration (Figures 6b and 7b), the calcium concentration rises with the shifted parabolic function, and the muscles are activated later, leading to a delayed isovolumetric contraction. With a wider parabolic Ca2+ concentration, the decrease rate is slower and more blood is ejected during systole. By analysing the influence of the wall stiffness on the PV diagrams, Figures 6c and 7c, when the stiffness is lower, we can see that the pressure during isovolumetric contraction and systole is lower, while the total volume during diastole is increased. By contrast, with higher wall stiffness, larger pressure is generated during isovolumetric contraction, as well as a smaller total volume during diastole. Regarding the influence of the inlet velocity value, as expected, when the outlet velocity is lower, less blood is ejected during systole. With 75% of the nominal inlet velocity, the total volume during diastole is also lower in comparison to the case with the nominal inlet velocity. A similar linear trend occurs when the inlet and outlet velocities are increased.