Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

© 2020 Creative Commons; the authors hold their copyright. Sudden cardiac death (SCD) from ventricular arrhythmias is a leading cause of mortality. Accurate arrhythmic risk stratification is vital for preventative clinical interventions. Ejection fraction (EF) is the primary metric used, but its accuracy is under debate, as many SCD cases exhibit preserved EF. Thus, identifying clear links between EF and arrhythmic risk is critical. Here, as a step forward, we investigate the ionic processes determining cellular pro-arrhythmic mechanisms and their relationship with active tension. A population of 2500 human ventricular electromechanical cellular models was created, and stimulated to produce pro-arrhythmic behaviour. We quantified their susceptibility to develop early afterdepolarizations (EADs) and action potential duration (APD) shortening, as key arrhythmic markers. The relationship between both arrhythmic markers and tension amplitude was found to be highly dependent on ionic mechanism. Variability in L-type calcium current was the primary determinant of active tension and arrhythmia susceptibility, alongside SERCA and hERG expression. Models with low tension could exhibit both high and low EAD susceptibility. APD shortening, however, displayed a weak positive correlation with active tension amplitude.

Original publication




Conference paper

Publication Date