Autonomic Unit, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust, London, UK.
Nemo SUD Clinical Centre, University Hospital "G. Martino", Messina, Italy.
Clin Auton Res. 2024 Jun;34(3):341-352. doi: 10.1007/s10286-024-01038-z. Epub 2024 May 20.
The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.
Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score.
A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)].
Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.
遗传性转甲状腺素蛋白淀粉样变的心肌病变和神经病变表型已得到广泛认可。心血管自主神经功能障碍的评估则不够系统和客观。
在遗传性转甲状腺素蛋白淀粉样变患者及疾病发作时（T0）和首次定量自主神经评估时（T1）的 TTR 变异无症状携带者队列中，记录自主神经和临床特征、定量心血管自主神经功能以及潜在的自主神经疾病进展预后标志物。根据多发性神经病残疾评分对周围神经病变的严重程度及其进展进行分层。
共纳入 124 名患者（111 名确诊为遗传性转甲状腺素蛋白淀粉样变，13 名 TTR 变异无症状携带者）。27%的患者在 T0 时报告有自主神经功能障碍症状。在自主神经检测时（T1），疾病持续时间为 4.5±4.0 年（均数±标准差）。78%的患者在 T1 时报告有自主神经功能障碍症状。75%的患者和 64%的 TTR 携带者通过功能检测发现心血管自主神经衰竭。从多发性神经病残疾 I/II 期进展到 III/IV 期的速度，在发病时有自主神经症状的患者似乎更快[2.33±0.56 年对比 4.00±0.69 年（均数±标准差）]。
遗传性转甲状腺素蛋白淀粉样变患者在发病后 4.5 年内，心血管自主神经功能障碍即较早且频繁发生。心血管自主神经衰竭在个体和无症状携带者中可能为亚临床，仅通过自主神经功能检测才能发现，这应被视为早期诊断和疾病进展的潜在生物标志物。
