Department of Cardiology, Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C. C. Iliescu', 3rd Cardiology Department, 258 Fundeni Street, Bucharest, 022328, Romania.
University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania.
ESC Heart Fail. 2021 Aug;8(4):2380-2396. doi: 10.1002/ehf2.13443. Epub 2021 Jun 5.
Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo-embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo-embolic risk) and the disease-modifying therapy.
心脏淀粉样变是一种由淀粉样物质积累引起的限制型心肌病，淀粉样物质由心脏细胞外空间中错误折叠的蛋白质片段组成。系统性淀粉样变的主要分类取决于引起非常异质疾病谱的淀粉样前体蛋白，但涉及心脏的主要淀粉样变类型是轻链 (AL) 和转甲状腺素蛋白淀粉样变 (ATTR)。AL 中，淀粉样前体由错误折叠的免疫球蛋白轻链组成，几乎可以涉及携带淀粉样变患者中预后最差的任何系统。然而，随着新型治疗方法（如蛋白酶体抑制剂和造血细胞移植）的使用增加，在及时诊断和开始治疗的情况下，这种情况在过去几年中已经有了显著改善。在存在严重心脏受累的情况下，血液科医生与心脏病专家密切合作，指导 AL 的治疗。转甲状腺素 (TTR) 是一种由肝脏产生的蛋白质，参与甲状腺激素，尤其是甲状腺素和视黄醇结合蛋白的运输。ATTR 是由于不同器官和系统（尤其是心脏和神经系统）中 TTR 淀粉样物质的积累而导致的。针对 ATTR 的特定治疗方法作用于 TTR 的各个水平，从合成到沉积：TTR 四聚体稳定、寡聚体聚集抑制、基因治疗、淀粉样纤维降解、抗淀粉样蛋白 P 抗体和抗 TTR 抗体。近年来，AL 和 ATTR 中的系统性淀粉样变治疗有了显著进展，改善了疾病预后。此外，最近的研究表明，及时治疗可以改善临床状况，并通过影像学（尤其是心脏磁共振）显示 AL 和 ATTR 中的淀粉样心肌浸润的消退。然而，由于系统性充血和低血压、血栓栓塞和出血风险平衡、患者虚弱以及一般预后不良之间的频繁关联，治疗心脏淀粉样变是一项复杂的任务。本综述的目的是描述在这个不断发展的领域中，心脏淀粉样变治疗的最新知识状况，分为心脏淀粉样变并发症（心力衰竭、节律和传导障碍以及血栓栓塞风险）的治疗和疾病修饰治疗。
