Division of Cardiology, Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles, California, USA.
Pharmacotherapy. 2021 Dec;41(12):1081-1091. doi: 10.1002/phar.2639. Epub 2021 Oct 30.
Transthyretin cardiac amyloidosis (ATTR-CA) has been recognized as an underdiagnosed and undertreated cause of heart failure with often unrecognized multiorgan involvement. Guideline development and the establishment of nonbiopsy criteria for diagnosis of ATTR-CA have led to an increased rate of diagnosis and hence patients referred for therapies. ATTR is a protein misfolding disorder where the TTR tetramer disassociates into monomers which form insoluble amyloid depositions in organs, including the heart. ATTR-CA can be due to autosomal dominant transmitted gene mutation or due to misfolding of wild-type TTR. Prior to 2019, there were no FDA-approved pharmacological treatments for ATTR-CA. Understanding of ATTR-CA pathogenesis has enabled development of targeted strategies with novel disease-modifying therapies. Current and emerging therapies for ATTR-CA include (1) TTR gene silencing (siRNA, ASO, CRISPR/Cas9), (2) TTR tetramer stabilization, and (3) TTR amyloid fibril degradation. This review focuses on the pathophysiology of ATTR-CA, diagnostic criteria, and addresses current and emerging treatments for this diverse disorder.
转甲状腺素蛋白心脏淀粉样变（ATTR-CA）是一种被低估和治疗不足的心力衰竭病因，常伴有多器官受累而未被识别。指南的制定和非活检诊断ATTR-CA 的标准的确立，导致诊断率提高，从而使更多患者接受治疗。ATTR 是一种蛋白质错误折叠疾病，其中 TTR 四聚体解离成单体，在包括心脏在内的器官中形成不溶性淀粉样沉积物。ATTR-CA 可由常染色体显性遗传基因突变引起，也可由野生型 TTR 错误折叠引起。在 2019 年之前，还没有 FDA 批准的治疗 ATTR-CA 的药物。对 ATTR-CA 发病机制的理解使靶向治疗策略和新型疾病修饰疗法得以发展。目前和新兴的 ATTR-CA 治疗方法包括：（1）TTR 基因沉默（siRNA、ASO、CRISPR/Cas9）；（2）TTR 四聚体稳定化；（3）TTR 淀粉样纤维降解。这篇综述重点介绍了 ATTR-CA 的病理生理学、诊断标准，并探讨了这种多样化疾病的现有和新兴治疗方法。
