PDF(Pubmed)
Abstract：
UNASSIGNED: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this \"cardiomyotoxicity\" are lacking.
UNASSIGNED: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
UNASSIGNED: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
UNASSIGNED: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
UNASSIGNED: NCT04294771 and NCT05454527.
UNASSIGNED: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
UNASSIGNED: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
UNASSIGNED: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
UNASSIGNED: NCT04294771 and NCT05454527.
摘要：
背景：免疫检查点抑制剂（ICI）与危及生命的心肌炎有关，但越来越多地认识到轻度表现。导致ICI-心肌炎的相同自身免疫过程可以表现为并发全身性肌炎，肌无力样综合征,和呼吸肌衰竭。缺乏这种“心肌毒性”的预后因素。
方法：多中心注册中心回顾性收集了2014-2023年期间17个国家的数据。多变量cox回归模型(风险比(HR)，[95％置信区间]）用于确定主要复合结局的危险因素：严重心律失常，心力衰竭,呼吸肌衰竭,和/或心肌毒性相关死亡。协变量包括人口统计学，合并症,心肌肌肉症状,诊断,和治疗。使用时间依赖性协变量，并估算缺失数据。得出并外部验证了基于点的预后风险评分。
结果：在748例患者中（67％为男性，年龄23-94），主要复合结局的30天发生率，心肌毒性死亡，总死亡率为33%，13%,分别为17%。通过多变量分析，主要复合结局与活动性胸腺瘤相关(HR=3.60[1.93-6.72]),心肌肉症状的存在（HR=2.60[1.58-4.28]），出现心电图时低QRS电压（HR≤0.5mV与>1mV=2.08[1.31-3.30]），左心室射血分数(LVEF)<50%(HR=1.78[1.22-2.60]),和肌钙蛋白升高增量(HR=1.86[1.44-2.39]，2.99[1.91-4.65],4.80[2.54-9.08],高于参考上限20倍、200倍和2000倍，分别)。使用这些参数制定的预后风险评分显示出良好的表现；30天主要结局发生率从3.9％（风险评分=0）逐渐增加到81.3％（风险评分=4）。该风险评分在两个独立的法国和美国队列中进行了外部验证。在外部法国队列中前瞻性地使用该风险评分，以识别在没有免疫抑制的情况下管理的低风险患者，这些患者没有心脏-肌肉毒性事件。
结论：ICI-心肌炎可表现为高发病率和高死亡率。心肌炎的严重程度与肌钙蛋白的大小有关，胸腺瘤,低QRS电压，沮丧的LVEF，和心肌症状.包含这些特征的风险评分表现良好。
方法：多中心注册中心回顾性收集了2014-2023年期间17个国家的数据。多变量cox回归模型(风险比(HR)，[95％置信区间]）用于确定主要复合结局的危险因素：严重心律失常，心力衰竭,呼吸肌衰竭,和/或心肌毒性相关死亡。协变量包括人口统计学，合并症,心肌肌肉症状,诊断,和治疗。使用时间依赖性协变量，并估算缺失数据。得出并外部验证了基于点的预后风险评分。
结果：在748例患者中（67％为男性，年龄23-94），主要复合结局的30天发生率，心肌毒性死亡，总死亡率为33%，13%,分别为17%。通过多变量分析，主要复合结局与活动性胸腺瘤相关(HR=3.60[1.93-6.72]),心肌肉症状的存在（HR=2.60[1.58-4.28]），出现心电图时低QRS电压（HR≤0.5mV与>1mV=2.08[1.31-3.30]），左心室射血分数(LVEF)<50%(HR=1.78[1.22-2.60]),和肌钙蛋白升高增量(HR=1.86[1.44-2.39]，2.99[1.91-4.65],4.80[2.54-9.08],高于参考上限20倍、200倍和2000倍，分别)。使用这些参数制定的预后风险评分显示出良好的表现；30天主要结局发生率从3.9％（风险评分=0）逐渐增加到81.3％（风险评分=4）。该风险评分在两个独立的法国和美国队列中进行了外部验证。在外部法国队列中前瞻性地使用该风险评分，以识别在没有免疫抑制的情况下管理的低风险患者，这些患者没有心脏-肌肉毒性事件。
结论：ICI-心肌炎可表现为高发病率和高死亡率。心肌炎的严重程度与肌钙蛋白的大小有关，胸腺瘤,低QRS电压，沮丧的LVEF，和心肌症状.包含这些特征的风险评分表现良好。
