Müller Maximilian Leo, Spethmann Sebastian, Messroghli Daniel, Brand Anna, Mattig Isabel, Hahn Katrin, Landmesser Ulf, Heidecker Bettina
Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; Amyloidosis Center Charité Berlin (ACCB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; Amyloidosis Center Charité Berlin (ACCB), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
JACC Adv. 2025 Feb;4(2):101568. doi: 10.1016/j.jacadv.2024.101568. Epub 2025 Jan 17.
Biomarker-based prognostic staging systems, including the National Amyloidosis Centre (NAC) and the Mayo staging systems, are widely-used but have only been validated for treatment-naive patients with cardiac transthyretin amyloidosis (ATTR-CA).
The purpose of this study was to assess the accuracy of the NAC and Mayo staging systems in patients with ATTR-CA treated with tafamidis.
A retrospective observational study following patients with ATTR-CA from initiation of tafamidis (baseline) to time of all-cause death was conducted. Patients were stratified according to the NAC and an adapted Mayo staging system incorporating high-sensitivity cardiac troponin T. Agreement was assessed using weighted Cohen's kappa. The staging systems' ability to identify subgroups with distinct overall survival was assessed using Kaplan-Meier analyses and pairwise log-rank tests.
A total of 251 patients with wild-type ATTR-CA treated with tafamidis were followed for a median of 521 (IQR: 262-842) days. There was substantial agreement (weighted kappa = 0.661; P < 0.001) between the NAC and the adapted Mayo staging system. Significant differences in estimated overall survival were observed across all disease stages of the adapted Mayo staging system (I vs II: P = 0.032; I vs III: P < 0.001; II vs III: P = 0.036). Accordingly, estimated overall survival was significantly lower in NAC III compared to NAC I (P < 0.001) and NAC II (P = 0.015). However, there was no significant difference between NAC I and NAC II (P = 0.340).
Both staging systems identified a distinct group of patients with ATTR-CA at the highest risk of death but only the adapted Mayo staging system could accurately distinguish between low- and intermediate-risk patients in the setting of disease-modifying treatment with tafamidis.
基于生物标志物的预后分期系统，包括国家淀粉样变性中心（NAC）分期系统和梅奥分期系统，被广泛应用，但仅在未经治疗的心脏转甲状腺素蛋白淀粉样变性（ATTR-CA）患者中得到验证。
本研究旨在评估NAC和梅奥分期系统在接受他法米地治疗的ATTR-CA患者中的准确性。
进行一项回顾性观察研究，对ATTR-CA患者从开始使用他法米地（基线）至全因死亡时间进行随访。患者根据NAC和纳入高敏心肌肌钙蛋白T的改良梅奥分期系统进行分层。使用加权科恩kappa系数评估一致性。使用Kaplan-Meier分析和两两对数秩检验评估分期系统识别具有不同总生存期亚组的能力。
共有251例接受他法米地治疗的野生型ATTR-CA患者，中位随访时间为521（IQR：262-842）天。NAC和改良梅奥分期系统之间存在高度一致性（加权kappa = 0.661；P < 0.001）。在改良梅奥分期系统的所有疾病阶段中，观察到估计总生存期存在显著差异（I期与II期：P = 0.032；I期与III期：P < 0.001；II期与III期：P = 0.036）。因此，与NAC I期（P < 0.001）和NAC II期（P = 0.015）相比，NAC III期的估计总生存期显著更低。然而，NAC I期和NAC II期之间无显著差异（P = 0.340）。
两种分期系统均识别出一组ATTR-CA死亡风险最高的患者，但仅改良梅奥分期系统能够在他法米地疾病修饰治疗背景下准确区分低风险和中度风险患者。
