The Vagal Link: Autonomic Nervous System Dysfunction in Cardiac Amyloidosis

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.

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Publication Details

Journal
Journal of Clinical Medicine
Published
2025-12-18
DOI
https://doi.org/10.3390/jcm14248963
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
Type
article
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article

The Vagal Link: Autonomic Nervous System Dysfunction in Cardiac Amyloidosis

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Journal of Clinical Medicine
Amyloidosis: Diagnosis, Treatment, Outcomes
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The Vagal Link: Autonomic Nervous System Dysfunction in Cardiac Amyloidosis

Antonio Crocamo, Alessandro D’Orsi, Maria Francesca Notarangelo, Livia Ruffini, Alberto Bettella, Giampaolo Niccoli, F Russo, Laura Torlai Triglia, Isabella Allegri, Angela Guidorossi, Federico Barocelli, Nicola Gaibazzi, Filippo Luca Gurgoglione, Eleonora Canu, Nicolò Pasini
article en

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.

Journal of Clinical MedicineVol. 14(24)
University of Parma (IT)
Openalex Percentile: Top 63%
Amyloidosis: Diagnosis, Treatment, Outcomes
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