Cardiac Sympathetic Innervation and Ventricular Arrhythmias in Structural Heart Disease: Current Peripheral Neuromodulation Therapies and Emerging Therapeutic Targets

Over the past several decades, substantial evidence has pointed to the role of the autonomic nervous system in the genesis and maintenance of ventricular arrhythmia. In particular, sympathetic activation has been shown to increase the risk of ventricular arrhythmia, particularly in the context of structural heart diseases, and is a key target of neuromodulatory therapies. Current peripheral sympathetic neuromodulatory approaches include temporary interventions, such as stellate ganglion block, proximal intercostal block, and thoracic epidural anaesthesia, as well as more definitive therapies, such as cardiac sympathetic denervation and renal denervation. Each of these approaches presents distinct strengths and limitations, as well as side effects that warrant careful consideration in clinical practice and highlight the need for more targeted strategies. Emerging interventions focusing on neuropeptide Y, sympathetic afferents ablation, high-frequency block of efferent nerves, and the restoration of sympathetic innervation after MI have shown promising potential. However, further research is needed to evaluate the feasibility and safety of these novel therapies prior to their implementation in patients with cardiovascular diseases.