Early cardiovascular autonomic failure in ATTRv predicts poor prognosis and may respond to disease-modifying therapy.

IF 7.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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.

ATTRv的早期心血管自主功能衰竭预示预后不良,可能对疾病改善治疗有反应。
背景:遗传性甲状腺转蛋白淀粉样变性(ATTRv)是一种危及生命但可治疗的疾病,表现为自主神经功能障碍。本研究探讨自主神经衰竭的进展,对治疗的反应,以及自主神经衰竭在ATTRv中的影响。方法:对126例(治疗40例)和12例无症状TTR变异携带者的临床特征和自主神经功能试验(AFT)结果进行评价。一个亚组进行了随访(FU) AFT。Kaplan-Meier估计比较了有和没有神经源性直立性低血压(nOH)的参与者的生存时间,并评估了其对死亡率的影响。结果:早期接受疾病修饰疗法(DMT)治疗的患者进展较慢,未发生nOH。在59例重复AFT患者中,自主神经功能障碍恶化,Valsalva比值下降(p = 0.002),甚至在疾病早期(p = 0.019;FU的中位病程为4年)。首次评估nOH预测较差的结果(nOH患者的平均生存时间为7.0年,而无nOH患者的平均生存时间为14.9年,p p = 0.001)。结论:自主神经功能障碍和nOH的早期发展是ATTRv患者生存期缩短的独立预测因素。自主检测是捕捉疾病进展的有价值的生物标志物。前瞻性研究需要证实DMT对自主神经功能障碍的益处。
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来源期刊
Amyloid-Journal of Protein Folding Disorders
Amyloid-Journal of Protein Folding Disorders 生物-生化与分子生物学
CiteScore
10.60
自引率
10.90%
发文量
48
审稿时长
6-12 weeks
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.
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