The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies

Cardiovasc Res. 2024 Jan 9:cvae009. doi: 10.1093/cvr/cvae009. Online ahead of print.ABSTRACTVentricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system (ANS) and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Specific pro-arrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada Syndrome, Early Repolarisation Syndrome, Long QT Syndrome and Catecholaminergic Polymorphic VT will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/-attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilising invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto- or sonogenetics allowing cell-sp...
Source: Cell Research - Category: Cytology Authors: Source Type: research