Autonomic Regulation Therapy in Heart Failure

Abstract

Autonomic regulation therapy (ART) is a rapidly emerging therapy in the management of congestive heart failure secondary to systolic dysfunction. Modulation of the cardiac neuronal hierarchy can be achieved with bioelectronics modulation of the spinal cord, cervical vagus, baroreceptor, or renal nerve ablation. This review will discuss relevant preclinical and clinical research in ART for systolic heart failure. Understanding mechanistically what is being stimulated within the autonomic nervous system by such device-based therapy and how the system reacts to such stimuli is essential for optimizing stimulation parameters and for the future development of effective ART.

Figure 1

This figure demonstrates the complexity of the neuronal hierarchy for cardiac control. Autonomic regulation therapy (ART) can target different structures in the cardiac neuronal hierarchy with promising results utilizing carotid sinus (CSN), dorsal column spinal cord (SCS), and cervical vagus electrical stimulation (VNS). Autonomic control can likewise be impacted by interrupting aberrant cardiac afferent signalling with Resinferatoxin (RTX) or by renal denervation. Sympath: sympathetic; Parasym: parasympathetic; LCN: local circuit neuron; DRG: Dorsal root ganglia; Aff. – afferent; T1-T4: first to 4th level of thoracic cord; Ang: Angiotensin; β: beta adrenergic receptor; M: muscarinic receptor; Gs and Gi: g proteins ; AC: adenylate cyclase; ATP: adenosine triphosphate; cAMP: cyclic-adenosine monophosphate; Neurite: sensory endings embedded in myocardium; decent: decentralization.