Anatomy of cardiac sensory innervation: A systematic review of current knowledge and implications for sex differences

PURPOSE: Sex differences in cardiac pain manifestation are reported in clinical studies, however, the underlying differences in the anatomy of cardiac sensory innervation remain unclear. METHODS: A systematic query across multiple datasets was conducted to extract all literature concerning anatomical studies on cardiac nociception with a focus on sex differences. RESULTS: Twenty-nine articles passed the inclusion criteria. Most studies applied nerve stimulation and nerve tracing techniques to study cardiac sensory innervation. Cardiac afferent fibres carry sensory information into the brainstem and the cervical and thoracic spinal cord segments C1-T11 with a main contribution to spinal segments T1-T4. Cervical spinal segments C1-C2, vagus nerve (CN X), and trigeminal nerve (CN V) appear to play an important role in cardiac pain referral to the jaw, neck and face regions. Only five studies discussed potential anatomical sex differences of cardiac afferents. These studies show that women are more likely to experience central convergence of cardiac nociceptive inputs at cervical levels, yet the underlying anatomy remains unknown. Additionally, a menopause-related decline of cardiac sensory innervation may contribute to delayed diagnosis in women compared to men. CONCLUSION: Our systematic review highlights the paucity of literature describing sex differences in the cardiac viscerosensory system. Dedicated research is required to address this knowledge gap and improve our understanding of sex-specific cardiovascular symptom presentation.