Abstract
Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy in which extracellular amyloid deposition leads to progressive structural and functional impairment. Beyond myocardial infiltration, growing evidence highlights the central role of autonomic nervous system dysfunction (ANS) —particularly the vagal nerve involvement—as a contributor to orthostatic intolerance, syncope, exercise limitation, arrhythmias, and reduced quality of life. Emerging data suggest that autonomic impairment may precede overt cardiac manifestations, offering a potential window for earlier recognition. This narrative review summarizes current knowledge on the mechanisms and clinical relevance of autonomic dysfunction in CA, emphasizing the novelty of the “vagal link” as a unifying framework connecting with a specific focus on the vagus nerve (VN) and its complex interplay with cardiac structure and function. We further discuss diagnostic approaches and the potential role of autonomic assessment in early detection, risk stratification, and personalized treatment strategies. A clearer understanding of vagal dysfunction may provide new insights into disease progression and identify opportunities for therapeutic innovation.