Electrophysiological Remodelling Secondary to Metabolic, Inflammatory and Cardiomyopathic Processes

Obesity, rheumatoid arthritis (RA) and gene-specific dilated cardiomyopathy (DCM) are common medical conditions. Small-scale studies have shown that these are associated with proarrhythmic changes on 12-lead electrocardiogram (ECG) and a higher risk of sudden cardiac death (SCD). However, these studies lack the deep electrophysiological phenotyping required to explain their observations. Electrocardiographic imaging (ECGi) is a non-invasive alternative to 12-lead ECG, by which epicardial potentials, electrograms and activation sequences can be recorded to study adverse electrophysiological modelling in greater depth and on a more focussed, subject-specific scale. Therefore, this study proposes to better define the risk of arrhythmia and understand the underlying adverse electrophysiological remodelling conferring this risk in three groups (obesity, RA and DCM). Firstly, data from two large, national repositories will be analysed to identify associations between routine clinical biomarkers and proarrhythmic 12-lead ECG parameters, to confirm adverse electrophysiological remodelling and a higher risk of arrhythmia. Secondly,ECGi will be performed before and after planned clinical intervention in obese and RA patients, and at baseline in titin-truncating variant (TTNtv)-positive and -negative DCM patients, to characterise the specific and potentially reversible conduction and repolarisation abnormalities that may underlie increased arrhythmic risk.