Abstract：
BACKGROUND: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.
METHODS: 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.
RESULTS: 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)].
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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)].
CONCLUSIONS: 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.
摘要：
背景：遗传性转甲状腺素蛋白淀粉样变性的心肌病和神经病学表型已得到公认。心血管自主神经功能障碍的系统和客观评估较少。
方法：自主神经和临床特征，定量心血管自主神经功能，在一组患有遗传性转甲状腺素蛋白淀粉样变性的个体中以及在疾病发作时(T0)和首次定量自主神经评估时(T1)的无症状TTR变异携带者中记录了疾病进展的潜在自主神经预后标志物.周围神经病变的严重程度及其进展与多发性神经病残疾评分分层。
结果：共纳入124例（111例确诊为遗传性转甲状腺素蛋白淀粉样变性，和13种TTR变体的无症状携带者)。在T0时，有27％的人报告了自主神经功能障碍的症状。在自主神经测试（T1）时，疾病持续时间为4.5±4.0年[平均值±标准偏差（SD）]。在T1时，有78％的人报告了自主神经功能障碍的症状。通过功能测试在75％的个体和64％的TTR携带者中发现了心血管自主神经衰竭。对于具有自主神经症状的个体，从多发性神经病残疾I/II期到III/IV期的进展率似乎较短[2.33±0.56对4.00±0.69年（平均值±SD）]。
结论：心血管自主神经功能障碍在遗传性转甲状腺素蛋白淀粉样变性患者发病4.5年内早期发生且频繁发生。心血管自主神经衰竭在个体和无症状携带者中可以是亚临床的，只有通过自主功能测试才能检测到，应被认为是早期诊断和疾病进展的潜在生物标志物。
方法：自主神经和临床特征，定量心血管自主神经功能，在一组患有遗传性转甲状腺素蛋白淀粉样变性的个体中以及在疾病发作时(T0)和首次定量自主神经评估时(T1)的无症状TTR变异携带者中记录了疾病进展的潜在自主神经预后标志物.周围神经病变的严重程度及其进展与多发性神经病残疾评分分层。
结果：共纳入124例（111例确诊为遗传性转甲状腺素蛋白淀粉样变性，和13种TTR变体的无症状携带者)。在T0时，有27％的人报告了自主神经功能障碍的症状。在自主神经测试（T1）时，疾病持续时间为4.5±4.0年[平均值±标准偏差（SD）]。在T1时，有78％的人报告了自主神经功能障碍的症状。通过功能测试在75％的个体和64％的TTR携带者中发现了心血管自主神经衰竭。对于具有自主神经症状的个体，从多发性神经病残疾I/II期到III/IV期的进展率似乎较短[2.33±0.56对4.00±0.69年（平均值±SD）]。
结论：心血管自主神经功能障碍在遗传性转甲状腺素蛋白淀粉样变性患者发病4.5年内早期发生且频繁发生。心血管自主神经衰竭在个体和无症状携带者中可以是亚临床的，只有通过自主功能测试才能检测到，应被认为是早期诊断和疾病进展的潜在生物标志物。
