Supervisors

Suitable for

Abstract

Prerequisites: Computational Medicine (recommended)

 

Abstract

Hypertrophic cardiomyopathy (HCM) presents a complex pattern of electrical, mechanical, and structural changes that evolve throughout the course of the disease. Early hypercontractility, altered calcium handling, myofilament dysfunction, and progressive hypertrophy interact across scales to shape clinically observed phenotypes including repolarisation abnormalities, diastolic impairment, and increased arrhythmic risk. Despite extensive clinical and experimental evidence, the mechanistic links between subcellular, tissue-level, and whole-organ dynamics in HCM progression remain poorly understood.

This project will use advanced multiscale electromechanical models of the human ventricle to investigate how specific forms of ionic remodelling, sarcomeric dysfunction, and structural adaptation contribute to stage-dependent alterations in cardiac function. Simulations will explore how progressive remodelling modifies action potential morphology, ventricular deformation, wall stress, pressure–volume loops, and surface ECG features. The student will also examine how different classes of therapeutic mechanisms influence electromechanical behaviour under early and advanced disease conditions.

Possible research directions include:
(i) modelling progressive ion-channel, calcium-handling, or myofilament changes characteristic of HCM;
(ii) quantifying electromechanical biomarkers of disease progression;
(iii) exploring how mechanism-specific therapeutic interventions alter cardiac performance across disease stages.

This project will contribute to a deeper mechanistic understanding of how HCM evolves and how therapy interacts with underlying biophysical abnormalities.

• References

[1] In-silico human electro-mechanical ventricular modelling and simulation for drug-induced pro-arrhythmia and inotropic risk assessment. https://doi.org/10.1016/j.pbiomolbio.2020.06.007

[2] Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy. https://doi.org/10.1016/j.yjmcc.2015.09.003