Stellate Ganglia: A Key Therapeutic Target for Malignant Ventricular Arrhythmia in Heart Disease

Malignant ventricular arrhythmias (VAs), such as ventricular tachycardia and ventricular fibrillation, are the cause of approximately half a million deaths per year in the United States, which is a common lethal event in heart disease, such as hypertension, catecholaminergic polymorphic ventricular tachycardia, takotsubo cardiomyopathy, long-QT syndrome, and progressing into advanced heart failure. A common characteristic of these heart diseases, and the subsequent development of VAs, is the overactivation of the sympathetic nervous system. Current treatments for VAs in these heart diseases, such as β-adrenergic receptor blockers and cardiac sympathetic ablation, aim at inhibiting cardiac sympathetic overactivation. However, these treatments do not translate into becoming efficacious as long-term suppressors of ventricular tachycardia/ventricular fibrillation events. As a key regulatory component in the heart, cardiac postganglionic sympathetic neurons residing in the stellate ganglia (SGs) release neurotransmitters (such as norepinephrine and NPY [neuropeptide Y]) to perform their regulatory role in dictating cardiac function. Growing evidence from animal experiments and clinical studies has demonstrated that the remodeling of the SG may be intimately involved in malignant arrhythmogenesis. This identifies the SG as a key potential therapeutic target for the treatment of malignant VAs in heart disease. Therefore, this review summarizes the role of SG in ventricular arrhythmogenesis and updates the novel targeting of SG for clinical treatment of VAs in heart disease.