Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation

Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1–T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation. •Cardiac autonomic innervation is highly variable and anatomical controversies exist.•The upper/lower limits of spinal segments involved in cardiac innervation can vary•Whether upper cervical ganglia are involved in sympathetic innervation is uncertain.•Thoracic cardiac nerves may emerge from ganglia lower than the 4th thoracic ganglia.•This variability may affect the outcome of cardiac neuronal modulation procedures.