State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Heart. 2024 Aug 26;110(18):1124-1132. doi: 10.1136/heartjnl-2024-324000.
Light chain cardiac amyloidosis (AL-CA) is associated with a high incidence of mortality. Big endothelin-1 (ET-1), the precursor of endothelial-vasoconstrictive ET-1, is closely related to the concentration of bioactive ET-1. Association between big ET-1 and prognosis of AL-CA has not yet been documented. The purpose of this study was to evaluate the prognostic value of big ET-1 for poor outcomes in moderate to severe AL-CA.
Big ET-1 levels were determined on admission in patients with newly diagnosed AL-CA with modified Mayo 2004 stage II or III. Primary outcome was all-cause mortality. The secondary outcomes included death from cardiac cause and the composite of the primary outcome or hospitalisations due to worsening heart failure.
Overall, 141 patients were retrospectively included (57 stage II, 34 stage IIIa, 50 stage IIIb). During a median follow-up time of 25.7 months, 84 (59.6%) patients died. Patients with big ET-1 levels of ≤0.88 pmol/L had longer survival than those with >0.88 pmol/L (median survival time: 34.1 months vs 15.3 months, log-rank p<0.001), which was also observed in the validation cohort (log-rank p=0.026). Higher big ET-1 levels were predictive for all-cause mortality after multivariable adjustment (HR 1.91, 95% CI 1.05 to 3.49, p=0.035). Big ET-1 levels added an incremental prognostic value over modified Mayo 2004 stage (C-index: from 0.671 to 0.696, p=0.025; integrated discrimination improvement 0.168, p=0.047).
Big ET-1 is a strong and independent predictor of mortality in patients with moderate to severe AL-CA, which may indicate a possible role for risk stratification in patients with this disease.
轻链心脏淀粉样变性（AL-CA）的死亡率较高。大内皮素-1（Big ET-1）是内皮血管收缩性内皮素-1 的前体，与生物活性内皮素-1 的浓度密切相关。Big ET-1 与 AL-CA 预后的相关性尚未有文献记载。本研究旨在评估 Big ET-1 对中重度 AL-CA 不良结局的预后价值。
在新诊断的改良 Mayo 2004 分期 II 或 III 期的 AL-CA 患者入院时测定 Big ET-1 水平。主要结局为全因死亡率。次要结局包括因心脏原因死亡和主要结局或因心力衰竭恶化而住院的复合结局。
共回顾性纳入 141 例患者（57 例分期 II，34 例分期 IIIa，50 例分期 IIIb）。中位随访时间为 25.7 个月期间，84 例（59.6%）患者死亡。Big ET-1 水平≤0.88 pmol/L 的患者的生存时间长于>0.88 pmol/L 的患者（中位生存时间：34.1 个月比 15.3 个月，log-rank p<0.001），这在验证队列中也得到了观察（log-rank p=0.026）。多变量调整后，较高的 Big ET-1 水平与全因死亡率相关（HR 1.91，95%CI 1.05 至 3.49，p=0.035）。Big ET-1 水平增加了改良 Mayo 2004 分期的附加预后价值（C 指数：从 0.671 增加至 0.696，p=0.025；综合判别改善 0.168，p=0.047）。
Big ET-1 是中重度 AL-CA 患者死亡率的强独立预测因子，这可能表明其在该疾病患者的风险分层中具有一定作用。
