Bradyarrhythmias: New mechanisms and treatments

Cardiac conduction system (CCS) disease is common, as are arrhythmias arising from the diseased CCS. Current therapy is limited to palliation by surgical implantation of a pacemaker or an intracardiac device, and in order to provide refined therapeutic strategies and better risk prediction for arrhythmic events, there is a need for an improved working understanding of how electrical excitability is regulated. In this seminar I will demonstrate how our laboratory has taken an active lead in the identification of new cellular pathways in the control of CCS electrophysiology, focusing on recent advances we have made in understanding dysfunctional pacemaking in endurance athletes, in aged and failing hearts, and in elucidating the circadian control of arrhythmogenesis. I will illustrate how epigenetic and transcriptional control mechanisms modulate pacemaker electrophysiology in these scenarios and delve into work we are currently undertaking towards translation of new fundamental insight on ion channel modulation into therapies for CCS disease and related arrhythmias.


Alicia D’Souza is a Reader in Cardiac Electrophysiology at the National Heart and Lung Institute at Imperial College London. Alicia’s research focuses on understanding the mechanisms by which ion channels in the hearts electrical wiring system are controlled. Trained as a cardiac physiologist during her PhD (2012), Alicia completed postdoctoral studies in the laboratory of Professor Mark Boyett at the University of Manchester investigating pacemaking in endurance athletes. Subsequently she was awarded a BHF Intermediate Fellowship in 2019 during which she established an independent research group that has advanced understanding of the cellular mechanisms that underlie conduction system function in health and in disease. Alicia’s work has been popularised in the media and led to numerous awards including the International Society for Heart Research/SERVIER Fellowship Prize, the (inaugural) Cairn Research ‘New and Notable’ Prize Lecture and The Physiological Society’s (inaugural) R Jean Banister Prize Lecture. Alicia’s group is also part of a Fondation Leducq Transatlantic Network of Excellence focused on novel pharmacotherapies for sinus node dysfunction.