De Michieli Laura, Lupi Alessandro, Sinigiani Giulio, Tietto Angela, Salvalaggio Alessandro, Branca Antonio, Da Pozzo Stefano, Rizzo Stefania, Cecchin Diego, Perazzolo Marra Martina, Berno Tamara, Corrado Domenico, Briani Chiara, Cipriani Alberto
Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, 35128 Padua, Italy.
Cardiology Unit, University Hospital of Padua, 35128 Padua, Italy.
J Clin Med. 2025 May 16;14(10):3481. doi: 10.3390/jcm14103481.
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive disease that has emerged as a significant cause of heart failure. Advances in the understanding of ATTR-CM pathophysiology have revolutionised its therapeutic landscape over the past decade, with the development of targeted therapies that are able to improve survival and quality of life. TTR stabilizers, such as tafamidis and acoramidis, can reduce TTR instability and subsequent amyloid fibril formation. Clinical trials have demonstrated their efficacy both in improving survival and quality of life in patients with ATTR-CM. Gene-silencing therapies using small interfering RNAs (siRNAs), such as patisiran and vutrisiran, or antisense oligonucleotide inhibitors (ASOs), such as inotersen and eplontersen, serve as powerful therapeutic options by decreasing TTR production; trials on patients with ATTR-CM have been recently published or are ongoing. Novel, emerging therapies aim to enhance fibril clearance using monoclonal antibodies, such as NI006, that target amyloid deposits in the myocardium, promoting their depletion, plausibly with regression of the structural and functional impairments caused by the disease. Concurrently, advancements in diagnostic modalities have facilitated earlier detection of this disease, allowing the timely initiation of treatment with a more significant impact on patients' survival and quality of life. Despite these strides, challenges remain, including the high cost of disease-modifying therapy and the need for response criteria to monitor treatment's efficacy. Future directions will involve improving patients' screening to achieve earlier diagnoses, optimising patients' selection for disease-modifying therapy and identifying criteria for the treatment's response or lack thereof to possibly consider therapy switch or associations. In this review, we will explore the more recent therapeutic advancements in ATTR-CM, starting from traditional heart failure therapies and moving to disease-modifying therapies with a detailed evaluation of the registration trials to explore the strengths and shortcomings of each treatment.
转甲状腺素蛋白（TTR）淀粉样变心肌病（ATTR-CM）是一种进行性疾病，已成为心力衰竭的重要病因。在过去十年中，对ATTR-CM病理生理学认识的进展彻底改变了其治疗格局，开发出了能够提高生存率和生活质量的靶向治疗方法。TTR稳定剂，如他氟米特和阿考米特，可以降低TTR的不稳定性及随后的淀粉样纤维形成。临床试验已证明它们在改善ATTR-CM患者的生存率和生活质量方面的疗效。使用小干扰RNA（siRNA）的基因沉默疗法，如帕替沙兰和缬草酰胺，或反义寡核苷酸抑制剂（ASO），如依诺特森和依普洛森，通过减少TTR的产生成为有力的治疗选择；最近已发表或正在进行针对ATTR-CM患者的试验。新型的、正在出现的疗法旨在使用单克隆抗体（如NI006）增强纤维清除，该抗体靶向心肌中的淀粉样沉积物，促进其消耗，可能会使疾病引起的结构和功能损伤消退。同时，诊断方式的进步有助于更早地检测出这种疾病，从而能够及时开始治疗，对患者的生存率和生活质量产生更显著的影响。尽管取得了这些进展，但挑战依然存在，包括疾病修饰疗法的高成本以及需要反应标准来监测治疗效果。未来的方向将包括改善患者筛查以实现更早诊断，优化疾病修饰疗法的患者选择，并确定治疗反应或无反应的标准，以便可能考虑更换治疗方法或联合治疗。在本综述中，我们将探讨ATTR-CM最近的治疗进展，从传统的心力衰竭治疗开始，转向疾病修饰疗法，并对注册试验进行详细评估，以探讨每种治疗方法的优缺点。
