Laura Sander, Giacomo Chiaro, Domenico Abelardo, Angelo Torrente, Gordon T Ingle, Patricia McNamara, Laura Watson, Carol J Whelan, Julian D Gillmore, Mary M Reilly, Christopher J Mathias, Valeria Iodice
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引用次数: 0
Abstract
Background: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening, but treatable disease presenting with autonomic dysfunction. This study investigates the progression of autonomic failure, response to treatment, and the impact of autonomic failure in ATTRv.
Methods: Clinical features and autonomic function test (AFT) results were evaluated in 126 patients (40 had treatment) and 12 asymptomatic TTR variant carriers. A subgroup had follow-up (FU) AFT. Kaplan-Meier estimates compared survival time between participants with and without neurogenic orthostatic hypotension (nOH), and logistic regression assessed its impact on mortality.
Results: Patients treated early with disease modifying therapies (DMT) had slower progression and did not develop nOH. In 59 individuals with repeat AFT, autonomic dysfunction worsened, with a decline in the Valsalva ratio (p = 0.002), even in early-stage disease (p = 0.019; median disease duration at FU 4 years). nOH at first assessment predicted worse outcome (mean survival time in individuals with nOH 7.0 vs. 14.9 years without nOH, p < 0.001) and death (OR = 5.27; 95%CI: 1.94 - 14.31; p = 0.001).
Conclusions: The early development of autonomic dysfunction and nOH is an independent predictive factor for shorter survival in ATTRv. Autonomic testing is a valuable biomarker to capture disease progression. Prospective studies need to confirm the benefit of DMT on autonomic dysfunction.
期刊介绍:
Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are:
etiology,
pathogenesis,
histopathology,
chemical structure,
nature of fibrillogenesis;
whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders.
Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.