Genetic Determinants Affecting the Relationship Between the Autonomic Nervous System and Sudden Death

The autonomic nervous system with its sympathetic and parasympathetic limbs and its neurohormones (nor)epinephrine and acetylcholine is a well-recognized modulator of cardiac electrophysiology. Inherited or congenital inhomogeneities of cardiac autonomic innervation, sympathovagal imbalance, autonomic nervous system hyperactivity, autonomic conflict, and/or genetic variants of α- and β-adrenergic receptors can predispose even structurally normal hearts to life-threatening arrhythmias. Remodeling of the autonomic nervous system found in patients with epilepsy and sudden infant death syndrome can also predispose to sudden death. The overlap between small fiber neuropathy, cardiac conduction disease, and Brugada syndrome possibly via genomic modulation is briefly addressed. Alternatively, the heart itself may be intrinsically susceptible to variations in autonomic nervous function. Inherited arrhythmia syndromes like the long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome can lead to sudden death under conditions of altered autonomic nervous system tone. In this chapter we focus on the genetic determinants affecting the relationship between the autonomic nervous system and sudden death.