Understanding the Mechanistic Links Between Mid-Wall Fibrosis and Arrhythmic Risk in Non-Ischemic DCM Using a Combined Modelling & Clinical Approach

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Non-ischemic dilated cardiomyopathy (NIDCM) is a common form of structural heart disease. It is characterised by enlargement of the heart's chambers, stretching and thinning the muscle walls, causing dilation. In many cases, the structure of the heart tissue itself changes with noticeable regions of fibrous tissue developing within the centre of the muscle wall. These structural changes associated with NIDCM can be seen and measured with the latest MR imaging techniques. Patients suffering from NIDCM have a very high chance of experiencing cardiac arrhythmias and associated sudden cardiac death. More specifically, a high-impact study from our Team showed a very clear link between these fibrous regions that develop within the centre of the heart wall in some NIDCM patients and death from arrhythmias. However, the reasons underlying this clear link between these structural changes associated with NIDCM and lethal arrhythmias is extremely poorly understood. Consequently, assessing this risk in patients and planning treatments remains a significant challenge. Understanding the link between structural changes identified in clinical MR data with the key physiological processes responsible for arrhythmias in NIDCM suggests the use of an image-based model to aid mechanistic interpretation. In this study, we aim to combine clinical MRI with advanced image analysis and computational modelling to improve our physiological understanding of the mechanisms underlying the link between changes in heart structure with cardiac arrhythmias. Gaining such knowledge will help to elucidate novel clinical risk-factors associated with NIDCM and help clinicians plan therapeutic interventions. Achieving our goals will provide more precise, informed decisions regarding the optimal way to treat an particular patient's heart, as well as the individual arrhythmia risk posed by a patient's NIDCM and the need for an implantable defibrillator, improving NIDCM survival rates and reducing health-service costs on unnecessary operations.