Periodic Reporting for period 1 - HI-SiMed (Hemodynamics in an Infarcted heart:from multi-physics Simulations to Medical analysis)
Reporting period: 2019-09-01 to 2021-08-31
Cardiac disease remains the most common cause of mortality in the industrialized world with risk factors including high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol intake. Detailed understanding of the heart functioning is fundamental for the improvement of diagnoses and therapies. In this framework, computational engineering is becoming an added value in medical research since it provides more details on heart pathologies and could predict the most favorable medical treatment. Over the last two decades, indeed, computational engineering has gained credibility and nowadays it is mature enough to produce reliable in silico experiments, which provide potentially unlimited access to hemodynamics data and dynamical features of the system that would be exceedingly difficult or impossible to obtain otherwise. Furthermore, novel technological solutions (prostheses or surgical procedures) can be virtually tested, thus avoiding the extensive use of hardware models or in vivo experiments on animals. On the other hand, a computational model yields a high-fidelity representation of the cardiovascular dynamics only when all the main features of the system are properly considered; these include actively (myocardium) and passively (valves and artery/vein walls) deforming nonlinearly elastic tissues, the electrophysiology of the heart with the propagation of the electrical signal over a complex path, the unsteady (pulsatile) of the blood flow, its non-Newtonian dynamics and the strong interplay among all the systems. With the above motivations, in this project we have developed and validated a multi-physics model of the left heart that can cope with the electrophysiology of the myocardium, its active contraction and passive relaxation, the dynamics of the valves (aortic and mitral) and the hemodynamics within ventricle, atrium and the first tract of the aorta.
In this project we have developed an innovative and versatile multi-physics model to simulate the left heart (LH) functioning. The pulsatile and transitional character of the hemodynamics is obtained by solving directly the incompressible Navier–Stokes equations using a staggered finite differences method. The code is complemented with various immersed boundary (IB) techniques to handle complex moving and deforming geometries. The structural mechanics is based on the Fedosov’s interaction potential method to account for the mechanical properties of the biological tissues, which are anisotropic and nonlinear. The electrophysiology, responsible for the active potential propagation in the cardiac tissue triggering the active muscular tension, is incorporated by means of a bidomain model that can account for the different cellular models of the various portions of the heart. All these models are three-way coupled with each other, thus capturing the fully synergistic physics that allows the heart to function continuously using only 8 W of power. The resulting electro-fluid–structure interaction (FSEI) code is tailored to investigate the pulsatile flow in an animated LH beating at 70 bpm. The LH is composed by realistic geometries of the left ventricle and atrium, whose active muscular contraction triggers a structural deformation of the endocardium that originates the hemodynamics, which, in turn, generates stresses on the surrounding cardiac tissue. The numerical framework also includes the bi-leaflet mitral valve, the three-leaflets aortic valve and the thoracic aorta, which are passive tissues experiencing continuous stretching and bending through the cardiac cycle.
The computational framework is seen to provide realistic cardiovascular simulations both in terms of muscular activation, intraventricular hemodynamics and wall shear stresses. In particular, we have shown the propagation of the transmembrane potential over the myocardium triggered by a localized electrical input in the Bachmann and His bundles. The consequent action potential and heart chambers depolarization yields an active muscular tension and tissue contraction that is oriented according to the local direction of the muscular fibers. Hence, the model reproduces also the vigorous three–dimensional twist of the left ventricle from the apex to the valvular plane observed in-vivo. This electro-mechanical activity of the LH chambers originates a complex hemodynamics and valve dynamics, which is in qualitative and quantitative agreement with in-vivo and ex-vivo measurements. The mitral valve connecting the left atrium and ventricle, opens during diastole and closes when the ventricle contracts, owing to the external hydrodynamics loads exerted on its leaflets. At the same time the mitral valve prevents an undesired back-flow of oxygenated blood during systole, the aortic valve opens and blood is propelled in the thoracic aorta. Furthermore, the numerics well reproduces the Wiggers diagram of a healthy human adult reported in medical atlas. This diagram shows the time variation over a heart beat of the pressure in the left ventricle, atrium and thoracic aorta, with the typical pressure variation of 0–120 mmHg in the ventricle. During a heart beat, the ventricular volume diminishes from the maximum (tele-diastolic) volume, which is given as input through the ventricle geometry, to its minimum (tele-systolic) value, which is not imposed and computed as part of the solution. This volume variation of the ventricle corresponds to an ejection fraction of about 60% and a cardiac output of 5.06 l/min, which are typical physiological values for the heart of a healthy adult.
The computational framework is seen to provide realistic cardiovascular simulations both in terms of muscular activation, intraventricular hemodynamics and wall shear stresses. In particular, we have shown the propagation of the transmembrane potential over the myocardium triggered by a localized electrical input in the Bachmann and His bundles. The consequent action potential and heart chambers depolarization yields an active muscular tension and tissue contraction that is oriented according to the local direction of the muscular fibers. Hence, the model reproduces also the vigorous three–dimensional twist of the left ventricle from the apex to the valvular plane observed in-vivo. This electro-mechanical activity of the LH chambers originates a complex hemodynamics and valve dynamics, which is in qualitative and quantitative agreement with in-vivo and ex-vivo measurements. The mitral valve connecting the left atrium and ventricle, opens during diastole and closes when the ventricle contracts, owing to the external hydrodynamics loads exerted on its leaflets. At the same time the mitral valve prevents an undesired back-flow of oxygenated blood during systole, the aortic valve opens and blood is propelled in the thoracic aorta. Furthermore, the numerics well reproduces the Wiggers diagram of a healthy human adult reported in medical atlas. This diagram shows the time variation over a heart beat of the pressure in the left ventricle, atrium and thoracic aorta, with the typical pressure variation of 0–120 mmHg in the ventricle. During a heart beat, the ventricular volume diminishes from the maximum (tele-diastolic) volume, which is given as input through the ventricle geometry, to its minimum (tele-systolic) value, which is not imposed and computed as part of the solution. This volume variation of the ventricle corresponds to an ejection fraction of about 60% and a cardiac output of 5.06 l/min, which are typical physiological values for the heart of a healthy adult.
The HI-SiMed project provides an advanced computational tool to study, with unprecedented resolution, the hemodynamics of the heart in physiological and pathological conditions and support medical decision.
For the first time the hemodynamics of the whole left heart is described in all its details by the state-of-the-art direct numerical simulation of the Navier-Stokes equations and could be used to improve prognoses for cardiovascular diseases. Furthermore, the computational model is predictive because the kinematic of the active heart chambers and valve leaflets are not imposed but come as a result of the full electro-fluid-structure coupling. The intrinsic interdisciplinarity of the project and the two-way transfer of knowledge from medicine to fluid dynamics, in order to simulate heart conditions at best, and from fluid dynamics to medicine, with the aim of improving patient treatments, naturally widens the impact of the research.
For the first time the hemodynamics of the whole left heart is described in all its details by the state-of-the-art direct numerical simulation of the Navier-Stokes equations and could be used to improve prognoses for cardiovascular diseases. Furthermore, the computational model is predictive because the kinematic of the active heart chambers and valve leaflets are not imposed but come as a result of the full electro-fluid-structure coupling. The intrinsic interdisciplinarity of the project and the two-way transfer of knowledge from medicine to fluid dynamics, in order to simulate heart conditions at best, and from fluid dynamics to medicine, with the aim of improving patient treatments, naturally widens the impact of the research.