Evaluation of autonomic dysfunction in hereditary transthyretin amyloidosis

Autonomic dysfunction is a common manifestation of hereditary transthyretin (ATTRv) amyloidosis that frequently appears early and has a major impact on disease severity, survival, and quality of life. Early detection of autonomic symptoms is paramount to avoid delayed diagnosis or misdiagnosis of ATTRv amyloidosis and thereby achieve timely interventions with novel therapies. We thus require a better understanding and recognition of the warning signs of autonomic nervous system involvement in patients with ATTRv amyloidosis.

According to the literature and the expertise of key opinion leaders on ATTRv amyloidosis, early signs and symptoms of autonomic dysfunction often include orthostatic hypotension, gastrointestinal disturbances, and cardiac and sudomotor sympathetic denervation. Assessment methods for a rapid and accurate diagnostic thus comprise blood pressure monitoring, nutritional status evaluation, cardiac imaging techniques, and pathological and neurophysiological tests assessing small fiber function. The COMPASS-31 and Norfolk QOL-DN tests allow assessment of the severity of autonomic dysfunction and its impact on quality of life, respectively.

The screening strategy for autonomic dysfunction should involve diverse neurological and non-neurological tests to encompass the wide variety of potential manifestations of autonomic dysfunction in ATTRv amyloidosis. Further studies addressing the correlations among different tests and their prognostic value in different TTR variants are required to establish a single standardized method or the minimum set of tests needed to assess autonomic dysfunction in ATTRv amyloidosis patients.