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This work aims at presenting a Discontinuous Galerkin (DG) formulation employing a spectral basis for two important models employed in cardiac electrophysiology, namely the monodomain and bidomain models. The use of DG methods is motivated by the characteristic of the mathematical solution of such equations which often corresponds to a highly steep wavefront. Hence, the built-in flexibility of discontinuous methods in developing adaptive approaches, combined with the high-order accuracy, can well represent the underlying physics. The choice of a semi-implicit time integration allows for a fast solution at each time step. The article includes some numerical tests to verify the convergence properties and the physiological behaviour of the numerical solution. Also, a pseudo-realistic simulation turns out to fully reconstruct the propagation of the electric potential, comprising the phases of depolarization and repolarization, by overcoming the typical issues related to the steepness of the wave front.

Cardiocirculatory mathematical models serve as valuable tools for investigating physiological and pathological conditions of the circulatory system. To investigate the clinical condition of an individual, cardiocirculatory models need to be personalized by means of calibration methods. In this study we propose a new calibration method for a lumped-parameter cardiocirculatory model. This calibration method utilizes the correlation matrix between parameters and model outputs to calibrate the latter according to data. We test this calibration method and its combination with L-BFGS-B (Limited memory Broyden - Fletcher - Goldfarb - Shanno with Bound constraints) comparing them with the performances of L-BFGS-B alone. We show that the correlation matrix calibration method and the combined one effectively reduce the loss function of the associated optimization problem. In the case of in silico generated data, we show that the two new calibration methods are robust with respect to the initial guess of parameters and to the presence of noise in the data. Notably, the correlation matrix calibration method achieves the best results in estimating the parameters in the case of noisy data and it is faster than the combined calibration method and L-BFGS-B. Finally, we present real test case where the two new calibration methods yield results comparable to those obtained using L-BFGS-B in terms of minimizing the loss function and estimating the clinical data. This highlights the effectiveness of the new calibration methods for clinical applications., Comment: 33 pages, 7 figures, submitted to International Journal for Numerical Methods for Engineering

Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19.

We present a novel mathematical model that simulates myocardial blood perfusion by embedding multiscale and multiphysics features. Our model incorporates cardiac electrophysiology, active and passive mechanics, hemodynamics, reduced valve modeling, and a multicompartment Darcy model of perfusion. We consider a fully coupled electromechanical model of the left heart that provides input for a fully coupled Navier-Stokes - Darcy Model for myocardial perfusion. The fluid dynamics problem is modeled in a left heart geometry that includes large epicardial coronaries, while the multicompartment Darcy model is set in a biventricular domain. Using a realistic and detailed cardiac geometry, our simulations demonstrate the accuracy of our model in describing cardiac perfusion, including myocardial blood flow maps. Additionally, we investigate the impact of a regurgitant aortic valve on myocardial perfusion, and our results indicate a reduction in myocardial perfusion due to blood flow taken away by the left ventricle during diastole. To the best of our knowledge, our work represents the first instance where electromechanics, hemodynamics, and perfusion are integrated into a single computational framework.

We present a loosely coupled scheme for the numerical simulation of the cardiac electro-fluid-structure interaction problem, whose solution is typically computationally intensive due to the need to suitably treat the coupling of the different submodels. Our scheme relies on a segregated treatment of the subproblems, in particular on an explicit Robin-Neumann algorithm for the fluid-structure interaction, aiming at reducing the computational burden of numerical simulations. The results, both in an ideal and a realistic cardiac setting, show that the proposed scheme is stable at the regimes typical of cardiac simulations. From a comparison with a scheme with implicit fluid-structure interaction, it emerges that, while conservation properties are not fully preserved, computational times significantly benefit from the explicit scheme. Overall, the explicit discretization represents a good trade-off between accuracy and cost, and is a valuable alternative to implicit schemes for fast large-scale simulations.

Two crucial factors for accurate numerical simulations of cardiac electromechanics, which are also essential to reproduce the synchronous activity of the heart, are: i) accounting for the interaction between the heart and the circulatory system that determines pressures and volumes loads in the heart chambers; ii) reconstructing the muscular fiber architecture that drives the electrophysiology signal and the myocardium contraction. In this work, we present a 3D biventricular electromechanical model coupled with a 0D closed-loop model of the whole cardiovascular system that addresses the two former crucial factors. With this aim, we introduce a boundary condition for the mechanical problem that accounts for the neglected part of the domain located on top of the biventricular basal plane and that is consistent with the principles of momentum and energy conservation. We also discuss in detail the coupling conditions that stand behind the 3D and the 0D models. We perform electromechanical simulations in physiological conditions using the 3D-0D model and we show that our results match the experimental data of relevant mechanical biomarkers available in literature. Furthermore, we investigate different arrangements in cross-fibers active contraction. We prove that an active tension along the sheet direction counteracts the myofiber contraction, while the one along the sheet-normal direction enhances the cardiac work. Finally, several myofiber architectures are analysed. We show that a different fiber field in the septal area and in the transmural wall effect the pumping functionality of the left ventricle.

In this work we address the issue of validating the monodomain equation used in combination with the Bueno-Orovio ionic model for the prediction of the activation times in cardiac electro-physiology of the left ventricle. To this aim, we consider our patients who suffered from Left Bundle Branch Block (LBBB). We use activation maps performed at the septum as input data for the model and maps at the epicardial veins for the validation. In particular, a first set (half) of the latter are used to estimate the conductivities of the patient and a second set (the remaining half) to compute the errors of the numerical simulations. We find an excellent agreement between measures and numerical results. Our validated computational tool could be used to accurately predict activation times at the epicardial veins with a short mapping, i.e. by using only a part (the most proximal) of the standard acquisition points, thus reducing the invasive procedure and exposure to radiation.

Since myocardial fibers drive the electric signal propagation throughout the myocardium, accurately modeling their arrangement is essential for simulating heart electrophysiology (EP). Rule-Based-Methods (RBMs) represent a commonly used strategy to include cardiac fibers in computational models. A particular class of such methods is known as Laplace-Dirichlet-Rule-Based-Methods (LDRBMs) since they rely on the solution of Laplace problems. In this work we provide a unified framework, based on LDRBMs, for generating full heart muscle fibers. First, we review existing ventricular LDRBMs providing a communal mathematical description and introducing also some modeling improvements with respect to the existing literature. We then carry out a systematic comparison of LDRBMs based on meaningful biomarkers produced by numerical EP simulations. Next we propose, for the first time, a LDRBM to be used for generating atrial fibers. The new method, tested both on idealized and realistic atrial models, can be applied to any arbitrary geometries. Finally, we present numerical results obtained in a realistic whole heart where fibers are included for all the four chambers using the discussed LDRBMs.

We consider a loosely coupled algorithm for fluid-structure interaction based on a Robin interface condition for the fluid problem (explicit Robin-Neumann scheme). We study the dependence of the stability of this method on the interface parameter in the Robin condition. In particular, for a model problem we find sufficient conditions for instability and stability of the method. In the latter case, we found a stability condition relating the time discretization parameter, the interface parameter, and the added mass effect. Numerical experiments confirm the theoretical findings and highlight optimal choices of the interface parameter that guarantee an accurate solution with respect to an implicit one.