Quantification of the influence of detailed endocardial structures on human cardiac haemodynamics and electrophysiology using hpc
- Autores: Federica Sacco
- Directores de la Tesis: Jazmin Aguado Sierra (dir. tes.), Oscar Camara Rey (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Jose María Guerra Ramos (presid.), Miguel Ángel González Ballester (secret.), Darrel Jay Swenson (voc.)
- Programa de doctorado: Programa de Doctorado en Tecnologías de la Información y las Comunicaciones por la Universidad Pompeu Fabra
- Materias:
- Texto completo no disponible (Saber más ...)
- Resumen
In the last decade computational modelling has been playing an important role as a non-invasive technology that may significantly impact the diagnosis as well as the treatment of cardiac diseases. As an example, the Food and Drugs Administration (FDA) has created new guidelines for in-silico trials for advancing new device pre-clinical testing and drug cardio-toxicity testing applications, since simulation studies have the potential to accelerate the discovery while reducing the need for expensive lab work and clinical trials. On the European side, the Avicenna Alliance4 aims to develop a road-map for in-silico clinical trials and establish the bases for the technology, methods and protocols required in order to make possible the use of computer simulations before the clinical trials. A common characteristic of the existing human cardiac models is that personalised geometries usually come from in-vivo imaging and the majority of computational meshes consider simplified ventricular geometries with smoothed endocardial (internal) surfaces, due to a lack of high-resolution, fast and safe in-vivo imaging techniques. Acquiring human high-resolution images would mean for the patient to undergo long, expensive and impractical scans, in the case of magnetic resonance images (MRI), or could present a risk for the patient’s health, in the case of computed tomography (CT), since this process involves a considerable amount of radiation. Smoothed ventricular surfaces are indeed considered by the majority of existing human heart computational models, both when modelling blood flow dynamics and electrophysiology. However the endocardial wall of human (and other mammals species) cardiac chambers is not smooth at all; it is instead characterised by endocardial sub-structures such as papillary muscles (PMs), trabeculations and false tendons (FTs). Additionally, fundamental anatomical gender differences can be found in cardiac sub-structural heart configuration as female hearts present less amount of FTs. Since there is little information about the role of endocardial substructures in human cardiac function, considering them in the human in-silico cardiac simulations would present a first step towards the understanding of their function. Additionally, comparing simulations results including sub-structural anatomical information with those obtained when considering simplified human cardiac geometries (representing common existing models) would shed a light on the errors introduced when neglecting human endocardial sub-structures. Another important aspect which is often ignored in in-silico simulations and could influence their outcome is gender phenotype. Female hearts have reduced resources for repolarization due to differences in K+ channels as compared to male phenotypes, leading to longer action potential durations (APDs). Longer APDs are consistent with clinical observation that females have longer QT intervals (time the heart takes to depolarize and repolarize) than males. Gender specificity can lead then to arrythmogenesis differences and so it may be important to consider different gender phenotypes when running in-silico electrophysiological simulations, in order to obtain results which are of clinical relevance and that can be compared to the subject-specific clinical data. In this thesis, therefore, we have created highly detailed human heart models from ex-vivo high-resolution MRI data, to study the role of cardiac sub-structures and gender phenotype in human cardiac physiology, through computational fluid dynamics (CFD) and electrophysiological high performance computing (HPC) simulations.
The contributions of the thesis can be summarised as follows:
• A pipeline of anatomically detailed cardiac volumetric mesh reconstruction was set up, starting from an ex-vivo high-resolution human heart MRI database.
• The impact of trabeculae and PMs on the blood flow within human left ventricular (LV) chambers was analysed using CFD simulations. This study demonstrated how the presence of trabeculae and PMs increase the intra-ventricular pressure drop, reduce thewall shear stress (WSS) and disrupt the main dominant single vortex, usually present in the smoothed endocardium models, generating secondary small vortices. Moreover, human female LVs were found to be less trabeculated than the male ones.
• A methodology to incorporate the effect of trabeculations into smoothed ventricular geometries was proposed. By adding a porous layer along the LV endocardial walls, both the intra-ventricular pressure drops and the vorticities, observed in the detailed models, could be reproduced also within smooth-walled LV geometries.
• The effect of detailed endocardial structures on human right ventricular (RV) haemodynamics was analysed using CFD simulations. RV endocardial walls are even more trabeculated than the LV ones, but even less is known about the effect of the presence of the endocardial structures on RV haemodynamics. In this study, it was shown how detailed endocardial structures increase the degree of RV intra-ventricular pressure drop, decrease the WSS and disrupt the dominant vortex creating secondary small vortices. In addition, turbulent blood flow was observed within the detailed RV chambers. Moreover, human female RV were less trabeculated and presented lower intra-ventricular pressure drops than the male ones.
• The influence of both highly detailed anatomical endocardial structures and gender phenotype on the electrophysiology of four biventricular, anatomically normal human heart models was investigated.
Furthermore, a comparison to smoothed-endocardium geometries was done to quantify the errors introduced by neglecting such structures. Simulations showed a significant repolarization times increase in the detailed female phenotype cases, coinciding with the observed QT prolongation in the female hearts. Moreover, the pseudo-electrocardiograms showed that the absence of trabeculations has an influence on the magnitude of the T waves. Finally, the presence of FTs shortcuts the signal propagation leading to faster total activation times.
