Amyloidosis Center, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Amyloid. 2021 Jun;28(2):91-99. doi: 10.1080/13506129.2020.1855134. Epub 2020 Dec 7.
Hereditary transthyretin amyloidosis is caused by pathogenic variants in the gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited.
This retrospective study investigated ATTRv-PN patients treated at the Amyloidosis Centre of Heidelberg University Hospital between November 1999 and July 2020. Clinical symptoms, survival, prognostic factors and efficacy of treatment with tafamidis were analysed. Neurologic outcome was assessed using the Coutinho ATTRv-PN stages, and the Peripheral Neuropathy Disability (PND) score.
Of 346 subjects with genetic variants, 168 patients had symptomatic ATTRv-PN with 32 different TTR variants identified. Of these, 81.6% had the late-onset type of ATTRv-PN. Within a mean follow-up period of 4.1 ± 2.8 years, 40.5% of patients died. Baseline plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥900 ng/l (HR 3.259 [1.421-7.476]; = .005) was the main predictor of mortality in multivariable analysis. 64 patients were treated with tafamidis and presented for regular follow-up examinations. The therapeutic benefit of tafamidis was more pronounced when treatment was started early in ATTRv-PN stage 1 (PND scores II vs. I; HR 2.718 [1.258-5.873]; = .011).
In non-endemic, mostly late-onset ATTRv-PN, cardiac involvement assessed by NT-proBNP is a strong prognosticator for overall survival. Long-term treatment with tafamidis is safe and efficacious. Neurologic disease severity at the start of treatment is the main predictor for ATTRv-PN progression on tafamidis.
遗传性转甲状腺素淀粉样变性是由 基因的致病性变异引起的，通常表现为心脏和其他器官功能障碍，以及快速进展的感觉运动和自主神经病（ATTRv-PN），导致严重残疾。虽然大多数前瞻性研究都集中在地方性 ATTRv-PN 上，但关于非地方性、主要是迟发性 ATTRv-PN 的真实世界数据有限。
本回顾性研究调查了 1999 年 11 月至 2020 年 7 月期间在海德堡大学医院淀粉样变性中心治疗的 ATTRv-PN 患者。分析了临床症状、生存、预后因素和塔法米迪治疗的疗效。使用 Coutinho ATTRv-PN 分期和周围神经病变残疾（PND）评分评估神经学结局。
在 346 名携带遗传变异的患者中，有 168 名患者出现有症状的 ATTRv-PN，其中 32 种不同的 TTR 变异被确定。其中，81.6%为迟发性 ATTRv-PN 类型。在平均 4.1±2.8 年的随访期间，40.5%的患者死亡。多变量分析显示，基线时脑钠肽前体（NT-proBNP）≥900ng/l（HR 3.259[1.421-7.476]； = .005）是死亡率的主要预测因素。64 名患者接受了塔法米迪治疗，并定期进行随访检查。在 ATTRv-PN 1 期（PND 评分 II 与 I；HR 2.718[1.258-5.873]； = .011）早期开始治疗时，塔法米迪的治疗效果更为明显。
在非地方性、主要是迟发性 ATTRv-PN 中，NT-proBNP 评估的心脏受累是总生存的有力预后因素。长期使用塔法米迪治疗是安全有效的。治疗开始时的神经疾病严重程度是塔法米迪治疗后 ATTRv-PN 进展的主要预测因素。
