Abstract
Cardiac resynchronisation therapy (CRT) is one of the few effective treatments for heart failure (HF). Through ventricular pacing, CRT synchronises cardiac electrical activation, leading to more efficient and effective cardiac pumping function and improved patient outcomes. However, between 30% and 50% of CRT patients do not experience clinical improvement.Three-dimensional computational models of cardiac electromechanics have the capacity to link anatomy and physiology to simulate the patient’s heart, and can then be used to predict and optimise CRT response. The growing interest in the role of the atria and major vessels in CRT response motivates the extension of previous models focused on the ventricles to the whole heart.
This thesis aims at building a framework for a four-chamber electromechanics model of the heart coupled with the whole circulatory system to optimise and predict response to CRT. Chapters 1 and 2 provide an introduction to the clinical problem of interest and a summary of the state of the art of cardiac modelling, respectively, while Chapter 3 presents all clinical data this thesis made use of. In Chapter 4, a semi-automatic pipeline to generate four-chamber heart meshes from computed tomography images is presented, followed by a mathematical framework to simulate ventricular activation and contraction on a four-chamber heart mesh. This is then used to study the effect of the pericardium on the ventricles, which is identified as a key feature for reproducing the patient’s physiological motion (Chapter 5). In Chapter 6, electrical activation and contraction of the whole heart are simulated, together with the effect of the pericardium on the atria and coupling with a closed-loop model for the systemic and pulmonary circulations based on the CircAdapt framework. The fully coupled model is used to study the effect of ventricular fibre orientation on atrial dynamics. Chapter 7 presents the first virtual cohort of four-chamber heart meshes, based on clinical data from twenty-four HF patients. This cohort is then used in Chapter 8 to carry out a CRT virtual clinical trial. Electrical activation of the ventricles is simulated during left bundle branch block and conventional and novel methods for CRT delivery. Patient responses are compared and the most efficient pacing strategies identified.
This thesis constitutes a significant step forward in four-chamber electromechanics simulations. The framework presented in Chapter 6 represents the first simulation platform that can simulate atrial contraction, ventricular contraction, pericardium boundary conditions, and circulatory system dynamics. The physiological boundary conditions imposed to represent the effect of the pericardium on the whole heart allow the model to replicate physiological motion of the atrioventricular plane. This leads to a better representation of the interaction dynamics between the atria and ventricles.
| Date of Award | 1 Jul 2021 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Steven Niederer (Supervisor) & Martin Bishop (Supervisor) |