Ruperti-Repilado Francisco Javier, van der Stouwe Jan Gerrit, Haaf Philip, Mueller Christian, Läubli Heinz, Pfister Otmar, Rothschild Sacha I, Kuster Gabriela M
Department Circulation, Thorax, Transplantation, Clinic of Cardiology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Department of Acute Medicine, Clinic of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Eur Heart J Case Rep. 2022 Aug 25;6(9):ytac353. doi: 10.1093/ehjcr/ytac353. eCollection 2022 Sep.
Immune checkpoint inhibitors (ICIs) have markedly improved outcome in various types of cancer. ICI-associated myocarditis is one of the most severe immune-related adverse events. In particular, high concentrations of cardiac troponin T (cTnT) are associated with a high risk of death and early detection and vigorous therapy with high-dose steroids may improve survival. However, chronic skeletal muscle disorders have been suggested as a non-cardiac source of elevated high-sensitivity cardiac troponin T (hs-cTnT) concentrations.
Here, we present the case of a 72-year-old patient with metastatic melanoma treated with nivolumab and ipilimumab, who developed symptomatic myositis [creatine kinase (CK) max. 3113 U/L]. Due to substantially elevated concentrations of hs-cTnT (max. 1128 ng/L, normal <14 ng/L, Elecsys), the patient was referred to the cardio-oncology unit for evaluation of concomitant myocarditis. The patient did not report any cardiac symptoms and there were no clinical signs of congestion or rhythm abnormalities. Concentrations of NT-proBNP were within the normal range. Echocardiography showed normal cardiac dimensions and normal systolic and diastolic function. Cardiac magnetic resonance imaging confirmed these findings and also showed no evidence of acute or post-inflammatory myocardial tissue changes. Absence of relevant cardiomyocyte injury was supported by determination of normal levels of cardiac troponin I concentrations and made endomyocardial biopsy in this severely ill patient unnecessary.
Our observation documents ICI-induced myositis as an alternative non-cardiac cause of hs-cTnT elevation. A global cardiologic approach employing clinical and cardiac magnetic resonance imaging data as well as NT-proBNP and cardiac troponin I helps to identify false positive hs-TnT elevation under ICI therapy.
免疫检查点抑制剂（ICI）显著改善了各类癌症的治疗效果。ICI相关心肌炎是最严重的免疫相关不良事件之一。特别是，高浓度的心肌肌钙蛋白T（cTnT）与高死亡风险相关，早期检测并使用大剂量类固醇进行积极治疗可能会提高生存率。然而，慢性骨骼肌疾病被认为是高敏心肌肌钙蛋白T（hs-cTnT）浓度升高的非心脏来源。
在此，我们报告一例72岁转移性黑色素瘤患者，接受纳武单抗和伊匹单抗治疗，出现症状性肌炎[肌酸激酶（CK）最高3113 U/L]。由于hs-cTnT浓度大幅升高（最高1128 ng/L，正常<14 ng/L，罗氏电化学发光免疫分析法），该患者被转诊至心脏肿瘤学科室评估是否合并心肌炎。患者未报告任何心脏症状，也没有充血或节律异常的临床体征。N末端B型利钠肽原（NT-proBNP）浓度在正常范围内。超声心动图显示心脏大小正常，收缩和舒张功能正常。心脏磁共振成像证实了这些结果，且未显示急性或炎症后心肌组织改变的证据。心肌肌钙蛋白I浓度正常，支持不存在相关心肌细胞损伤，因此无需对该重症患者进行心内膜活检。
我们的观察证明ICI诱发的肌炎是hs-cTnT升高的另一种非心脏原因。采用临床和心脏磁共振成像数据以及NT-proBNP和心肌肌钙蛋白I的全面心脏病学方法有助于识别ICI治疗下hs-TnT升高的假阳性情况。
