Abstract：
Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.
摘要：
免疫检查点抑制剂相关性心肌炎（ICIs-M）是一种罕见且高度致命的免疫相关不良事件（irAE），在常见的irAE中。本研究旨在寻找能够准确反映疾病状态和预后的循环生物标志物。根据ICIs相关心肌炎的诊断标准，纳入48例ICIs-M患者。对于所有入选的患者，从医疗系统中回顾性地提取了有价值的信息，主要包括人口统计信息，肿瘤信息和实验室检查。随访期定义为首次诊断ICIs-M后30天。在这项研究中,ICIs-M的30日死亡率为24.4%.在使用多变量分析工具调整潜在的混杂因素后，我们证明了生物标志物在预测ICIs-M患者30天死亡率方面的卓越表现，包括PLT(危险比(HR)，1.07；95%置信区间（95CI），1.01-1.14；p=0.028)，ALT(HR,1.23；95CI，1.06-1.41；p=0.005），AST(HR,1.06；95CI，1.01-1.10；p=0.015），LDH(HR,1.15；95CI，1.04-1.26；p=0.004），肌钙蛋白I(HR,1.44；95CI，1.09-1.89；p=0.009），PLR（血板/淋巴细胞）（HR，1.04；95%CI，1.01-1.07；p=0.024），LAR（乳酸脱氢酶/白蛋白）（HR，1.05；95CI，1.01-1.09；p=0.012），和AAR（天冬氨酸转氨酶/白蛋白）（HR，1.18；95CI，1.00-1.39；p=0.048）。对受试者工作特性的分析表明，曲线下面积（AUC）大于或等于0.80的生物标志物为LDH（截止值，724.5；AUC，0.86；95CI，0.75-0.97），LAR(截止值，18.11；AUC，0.87；95CI，0.76-0.97），肌钙蛋白I(临界值，0.87；AUC，0.80；95CI，0.62-0.99），和AAR(截止值，1.52;AUC,0.80；95CI，0.61-0.98）。LDH,LAR,肌钙蛋白I,AAR和AAR是一组有前景的生物标志物,在预测免疫相关性心肌炎30天死亡率方面表现出优异的预测能力。
