Background: Cardiomyopathy is a major cause of death in patients with systemic transthyretin amyloidosis. Long term effect of therapy designed to inhibit hepatic production of the amyloid precursor has not been established in cardiomyopathy. The purpose of this study was to evaluate the long term safety and efficacy of transthyretin specific antisense oligonucleotide therapy, inotersen, in transthyretin cardiomyopathy.Methods: Patients with hereditary or wildtype transthyretin cardiomyopathy (NYHA I-III) with an LV wall thickness [Formula: see text]1.3 cm and clinical evidence of congestive heart failure were eligible for this single centre, open label protocol. Safety and cardiac structural and functional parameters were prospectively studied.Results: As of October 2018, 33 subjects have entered the study. Twenty have completed 1 year, 16 have completed 2 years, and 14 have completed three years. At the 2 year time point, mean LV mass decreased by 8.4% as measured by MRI, and exercise tolerance increased by 20.2 metres as measured by 6 minute walk test. Further positive indicators were noted at 3 years, with LV mass decreasing by 11.4% and 6MWT increasing by 16.2 metres.Conclusion: Long term treatment of amyloid cardiomyopathy with inotersen is safe and effective in inhibiting progression and potentially reversing amyloid burden.

中文翻译：

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甲状腺素治疗转甲状腺素蛋白淀粉样心肌病。

背景：心肌病是全身性甲状腺素转运蛋白淀粉样变性病患者的主要死亡原因。在心肌病中尚未确立旨在抑制淀粉样蛋白前体在肝脏中产生的治疗的长期效果。这项研究的目的是评估转甲状腺素蛋白特异性反义寡核苷酸疗法inotersen在转甲状腺素蛋白心肌病中的长期安全性和有效性。见文字] 1.3 cm和充血性心力衰竭的临床证据均符合该单一中心，开放标签方案。结果：截至2018年10月，已有33位受试者参加了这项研究。20年完成了1年，16个已经完成2年，而14个已经完成3年。在2年的时间点，通过MRI测得的平均LV质量下降了8.4％，通过6分钟步行测试测得的运动耐量增加了20.2米。在3年时还发现了其他积极指标，左室重量减少了11.4％，而6MWT增加了16.2米。结论：用inotersen长期治疗淀粉样变性心肌病是安全有效的抑制进展并可能逆转淀粉样变性负担。