Analysis of cardiac electrogram morphology and its relationship with the underlying substrate using biological models and in silico tools
File(s)
Author(s)
Li, Shengzhe
Type
Thesis or dissertation
Abstract
The extracellular contact electrogram is a valuable tool for understanding the relationship between the electrical activity and the structural characteristics of the myocardium. Commonly used in the cardiac catheterisation laboratory, it provides important information on the electrical behaviour and conduction properties of the heart. Although the morphology of the electrogram can reveal important insights into conduction abnormalities and electrophysiological disturbances, its interpretation remains challenging due to the complex relationship between the electrical signals of the heart and its underlying structural and functional properties. The central hypothesis of this thesis is that the left ventricular electrogram morphology is affected by the underlying substrates and that these electrical activities can be effectively modelled using in-silico simulations.
To test this hypothesis, several biological models were characterised. Unipolar electrograms were recorded from rat and human biomimetic myocardial slices, neonatal rat ventricular myocytes, and ex-vivo porcine whole hearts. These electrograms were analysed using custom-developed signal processing and feature extraction tools to examine their morphological characteristics. In parallel, fluorescence microscopy was used to observe structural and functional changes, which were then quantified and correlated with electrogram features. This analysis revealed significant correlations between electrogram morphology and the underlying myocardial substrates, illustrating how conditions such as heart failure can alter both the structural and functional underlying myocardial substrates of the heart, ultimately affecting the electrogram.
In addition to the experimental work, computational models were developed to further explore the link between myocardial substrates and electrogram morphology. A multi-domain computational model and a continuum model of action potential propagation were used, incorporating gap junction remodelling to simulate the effects of structural changes on the electrogram. These simulations, performed using the spectral/hp element method, successfully demonstrated the feasibility of integrating substrate-related effects into numerical models of electrogram behaviour.
To test this hypothesis, several biological models were characterised. Unipolar electrograms were recorded from rat and human biomimetic myocardial slices, neonatal rat ventricular myocytes, and ex-vivo porcine whole hearts. These electrograms were analysed using custom-developed signal processing and feature extraction tools to examine their morphological characteristics. In parallel, fluorescence microscopy was used to observe structural and functional changes, which were then quantified and correlated with electrogram features. This analysis revealed significant correlations between electrogram morphology and the underlying myocardial substrates, illustrating how conditions such as heart failure can alter both the structural and functional underlying myocardial substrates of the heart, ultimately affecting the electrogram.
In addition to the experimental work, computational models were developed to further explore the link between myocardial substrates and electrogram morphology. A multi-domain computational model and a continuum model of action potential propagation were used, incorporating gap junction remodelling to simulate the effects of structural changes on the electrogram. These simulations, performed using the spectral/hp element method, successfully demonstrated the feasibility of integrating substrate-related effects into numerical models of electrogram behaviour.
Version
Open Access
Date Issued
2025-06-16
Date Awarded
2025-10-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Kanagaratnam, Prapa
Chowdhury, Rasheda
Wang, Liliang
Cantwell, Christopher
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)