Autonomic modulation of ventricular electrical activity: recent developments and clinical implications

Abstract

Purpose This review aimed to provide a complete overview of the current stance and recent developments in antiarrhythmic neuromodulatory interventions, focusing on lifethreatening vetricular arrhythmias. Methods Both preclinical studies and clinical studies were assessed to highlight the gaps in knowledge that remain to be answered and the necessary steps required to properly translate these strategies to the clinical setting. Results Cardiac autonomic imbalance, characterized by chronic sympathoexcitation and parasympathetic withdrawal, destabilizes cardiac electrophysiology and promotes ventricular arrhythmogenesis. Therefore, neuromodulatory interventions that target the sympatho-vagal imbalance have emerged as promising antiarrhythmic strategies. These strategies are aimed at different parts of the cardiac neuraxis and directly or indirectly restore cardiac autonomic tone. These interventions include pharmacological blockade of sympathetic neurotransmitters and neuropeptides, cardiac sympathetic denervation, thoracic epidural anesthesia, and spinal cord and vagal nerve stimulation. Conclusion Neuromodulatory strategies have repeatedly been demonstrated to be highly effective and very promising anti-arrhythmic therapies. Nevertheless, there is still much room to gain in our understanding of neurocardiac physiology, refining the current neuromodulatory strategic options and elucidating the chronic effects of many of these strategic options.

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation

“…Vagus nerve stimulation (VNS) has proven to be an organ-protective and potential alternative therapeutic approach to treat various pathological conditions by restoration of the autonomic balance, such as atrial fibrillation 13 , ventricular arrhytmias 15 , persistent tachycardia 35 , and heart failure 2,36,37 . However, previous studies have also shown that in-vivo VNS is still mainly performed at the cervical level of the VN, which has shown to often provoke unwanted off-target effects, and consequently limits the therapeutic efficacy of those applications 30,38,39 .…”

The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology

“…Animal models have helped us to better understand how endogenous circadian mechanisms, as well as daily rhythms in the environment and behaviour, each impact 24 h rhythms in cardiac electrophysiology. Additional studies translating this work in people are needed, but these studies suggest that targeting endogenous circadian mechanisms, as well as modifying the timing of environmental signals and behaviour, could lead to additional therapeutic strategies that can mitigate arrhythmogenic risk in people with different types of heart disease (Delisle et al, 2021a(Delisle et al, , 2021bTsimakouridze et al, 2015;van Weperen et al, 2021).…”

Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC—endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society

“…Electrical storm recurrences are common, especially within the first year after the acute event. The pro-arrhythmic effect of sympathetic–parasympathetic imbalance may still play an important role beyond the acute phase, 249 , 326 and initiation of long-term BB therapy is appropriate. 26 , 149 …”