Selvanayagam Joseph B, Hawkins Philip N, Paul Biju, Myerson Saul G, Neubauer Stefan
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
J Am Coll Cardiol. 2007 Nov 27;50(22):2101-10. doi: 10.1016/j.jacc.2007.08.028. Epub 2007 Nov 13.
Cardiac amyloidosis describes clinically significant involvement of the heart by amyloid deposition, which may or may not be associated with involvement of other organs. The purpose of this review is to summarize the current state of evidence for the effective evaluation and management of cardiac amyloidosis. Acquired systemic amyloidosis occurs in more than 10 per million person-years in the U.S. population. Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis. Furthermore, newer echocardiographic techniques such as strain and strain rate imaging can demonstrate impairment in longitudinal function before ejection fraction becomes abnormal. Recent observational studies also suggest that cardiovascular magnetic resonance imaging yields characteristic findings in amyloidosis, offering promise for the early detection of cardiac involvement, and the presence of detectable cardiac troponin and elevated B-type natriuretic peptide in serum of affected patients portends an adverse prognosis. Management strategies for cardiac amyloid are largely based on nonrandomized single-center studies. One of the few published randomized studies shows the superiority of oral prednisolone and melphalan compared with colchicine in systemic AL amyloidosis. Intermediate-dose infusional chemotherapy regimes (such as vincristine, adriamycin, and dexamethasone) and high-dose chemotherapy with peripheral stem cell rescue have been used widely, but treatment-related mortality remains substantial with chemotherapy. Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs.
心脏淀粉样变性是指淀粉样物质沉积导致临床上显著的心脏受累，这种沉积可能与其他器官受累有关，也可能无关。本综述的目的是总结目前关于心脏淀粉样变性有效评估和管理的证据现状。在美国人群中，获得性系统性淀粉样变性的发病率超过每百万人年10例。虽然没有单一的非侵入性检查或异常对心脏淀粉样变性具有诊断特异性，但病例对照研究表明，超声心动图显示左心室壁增厚、双房扩大、回声增强，同时心电图电压降低，强烈提示心脏淀粉样变性。此外，应变和应变率成像等更新的超声心动图技术可以在射血分数异常之前显示纵向功能受损。最近的观察性研究还表明，心血管磁共振成像在淀粉样变性中产生特征性表现，为早期发现心脏受累提供了希望，并且在受影响患者的血清中检测到心脏肌钙蛋白和B型利钠肽升高预示着不良预后。心脏淀粉样变性的管理策略主要基于非随机的单中心研究。少数已发表的随机研究之一表明，在系统性AL淀粉样变性中，口服泼尼松龙和马法兰优于秋水仙碱。中等剂量的输注化疗方案（如长春新碱、阿霉素和地塞米松）以及外周干细胞救援的大剂量化疗已被广泛应用，但化疗相关的死亡率仍然很高。最近的研究还表明，使用抗体、合成肽和小分子药物来稳定淀粉样蛋白原性蛋白质的天然结构、抑制原纤维形成以及破坏已形成的沉积物等策略具有前景。
