Design of a multi-scale canine-specific model of cardiac electromechanics : a step toward patient-specific modeling

Motivated by the growing wealth of biological data and the increasing pathophysiological knowledge at different scales, spectacular progress have been made in comprehensive modeling to understand the complex nature of biological organs, such as the heart. Today, the complexity of cardiac electromechanical models is outstanding; they couple multiple scales, from a genetic level to cellular, organ, and until including whole body interactions, and they already proved their importance to understand the pathophysiology of human diseases such as heart failure and dyssynchrony (Kerckhoffs et al., 2008). However these models fail to faithfully reproduce the behavior of an individual heart. This last decade, a relatively novel approach has emerged as an excellent answer to that drawback: the specific modeling! With the continual grow of computing power; we strongly believe that we now have reached a state where specific models are increasingly feasible and almost ready to be used clinically to assist the physicians. In this study, we present the methodology developed to design a realistic whole heart dog-specific model that includes the four most important components for models of cardiac electromechanics: anatomical, electrophysiology, mechanics and hemodynamics. To specifically fit these components into the model, mechanical anisotropy of the myocardium, active and passive tissue properties, and muscle activation sequence were measured during canine experimental studies. Additionally, high-end imaging tools such as Magnetic Resonance Imaging, Diffusion Tensor Imaging, and micro Computed Tomography were performed on each animal to acquire specific morphological details on anatomy and muscle fibers orientation. Collectively, the methods presented in this paper will lay the framework toward the development of cardiac patient-specific models. These models will be invaluable clinically to predict and optimize the outcome of therapies and interventional surgery on patients

Effects of a stiffened arterial tree on ventricular-arterial coupling in healthy and diseased hearts

David Jegger

In this thesis we study ventricular-arterial coupling in rodents under the influence of arterial stiffening and myocardial infarction (MI), combination of the two considered as a novel cardiovascular research model for diseased hearts pumping against an aged, stiffened arterial tree. The stiffened arterial tree yields isolated systolic hypertension and is obtained by administration of vitamin D and nicotine (VDN). The investigation cardiac performance and ventricular-arterial coupling using such a combined model (VDN/MI) is of particular relevance to cardiac research, as cardiac disease in elderly often takes place in presence of a atherosclerotic or stiff arterial tree.. The thesis consists of an Introduction, 4 scientific papers and a brief Conclusion. The Introduction is an overview of the epidemiology of heart failure, structure and functional changes that occur during MI and VDN, material and methods used in evaluating cardiac function invasively and non-invasively (using trans-thoracic echocardiography, TTE), methods for evaluating arterial function, and finally an overview of the interaction between the heart and vessels. Paper 1: This paper addresses the issue of the universality of the normalized time-varying elastance curve. It is demonstrated that the waveform of the normalized time-varying elastance curve (En(tn)) is qualitatively comparable between the control and MI hearts, however, when En(tn) is compared quantitatively between the two groups, statistical significance is found at the ejection phase and during diastole. These differences need to be taken into account when assessing cardiac contractility based on a generalized En(tn) in different animal models or in the human in different physiological or pathological states. Paper 2: Using trans-thoracic echo (TTE), we were able to follow serial changes of cardiac function post MI using two novel parameters, the myocardioal performance index (MPI) and its ratio to left ventricular fractional shortening (LVFS/MPI), both indices being monitor successfully and as efficiently as other classical TTE parameters. More so, LVFS/MPI visually expressed better the serial modifications in cardiac function. Both MPI and LVFS/MPI were correlated to the load-independent contractile parameter, PRSW, and to the preload parameter, LVEDP, being thus pertinent in following preload changes post MI. Finally, chamber remodeling post MI can successfully be followed due to the fact that ESV and EDV both correlate to MPI and LVFS/MPI. Paper 3: We studied hemodynamics, arterial function, cardiac function and ventricular-arterial coupling in a rat model of reduced arterial compliance. The results show that arterial stiffening after VDN treatment provokes important changes in vascular impedance and wave reflections, leading to isolated systolic hypertension and LV hypertrophy, Ventricular-arterial coupling was also altered. The effects are quantitatively similar to those of arterial stiffening with age. Paper 4: We studied changes in cardiac geometry, structure and function in response to MI in control and VDN-treated (stiffened aorta) rats. The combined VDN/MI model showed the largest compromise in cardiac structure and function and exhibited the strongest biochemical signs of heart failure as compared to all other groups. The addition of MI on top of a raised afterload, seems to have accelerated the progression of heart failure. Vascular alterations also reflected well a model of ageing and calcification. This combined pathology model of failing hearts in presence of a stiff arterial tree might be fruitful in better understanding the evolution of disease and may help improving or developing novel treatment therapies. The Conclusion chapter summarizes the findings of the thesis and brings into perspective their importance and future relevance into cardiovascular research models.

EPFL2006

Reduced order models for the simulation of pathological heart valves

Lidia Stepanova

Numerical modeling of the human cardiovascular system (CVS) represents an active branch of research which allows the medical specialists to advance in understanding of underlined processes of blood circulation and the heart work at any scale, moreover, it helps to analyze the potential problems which can arise in the CVS by modifying the parameters inside the mathematical models. Due to inability to capture in details the pressure and flow parameters without invasion into heart chambers, the process of diagnosing heart diseases can become very complicated, the limited data on atrial pressure and cardiogram results can give only overall representation of the heart condition and the exactness of the diagnosis is based mainly on experience of the doctor. Nevertheless, the development of numerical models of CVS helps to get better understanding on processes which can cause particular disease (reverse flow leakage in heart chambers, improper contraction of heart muscles due to infarction of tissue). Mathematical model allows the analysis of all physical values of the system during the heart beat as well as possibility to adjust individual parameters specific to each patient. Therefore, it becomes an efficient tool for doctors to diagnose properly the heart disease, to assign the necessary treatment and surgery, and to predict the effect of implanting cardiac-assist devices.

2013

Effects of a stiffened arterial tree on ventricular-arterial coupling in healthy and diseased hearts

David Jegger

EPFL2006