免疫检查点抑制剂相关重症心肌炎患者临床特征分析

Clinical characteristics analysis of patients with severe immune checkpoint inhibitors related myocarditis

目的分析免疫检查点抑制剂(ICIs)相关重症心肌炎患者临床特征。方法回顾性收集2020年4月至2022年4月在复旦大学附属中山医院肿瘤心脏病多学科门诊就诊和随访的50例ICIs相关心肌炎患者的临床资料,年龄为(63.7±10.8)岁,其中男37例,女13例;根据严重程度将患者分为轻症组(37例)和重症组(13例),分析两组患者的基础特征、临床表现、实验室检查、辅助检查、合并其他免疫相关不良事件(irAEs)、治疗和转归等差异。结果轻症组和重症组患者的免疫治疗时间[M(Q_(1),Q_(3))]分别为81(49,134)和24(20,116)d(P<0.05)。重症组心肌肌钙蛋白[0.605(0.317,1.072)μg/L]、氨基末端脑钠肽前体[1126(386,1744)ng/L]、肌型肌酸激酶[78(48,238)U/L]、肌型肌酸激酶[240(45,6543)U/L]水平比轻症组[分别为0.104(0.045,0.189)μg/L、237(39,785)ng/L、24(20,33)U/L、108(72,168)U/L]高(均P<0.05)。重症组左心室射血分数[64%(57%,65%)]比轻症组[66%(63%,69%)]低(P<0.05),传导阻滞发生率(4例,4/13)、室壁运动异常发生率(4例,4/13)、合并ICIs相关心肌炎发生率(10例,10/13)、ICIs相关肝炎发生率(4例,4/13)和ICIs相关神经毒性发生率(4例,4/13)比轻症组[分别为2.7%(1例)、5.4%(2例)、43.2%(16例)、5.4%(2例)、2.7%(1例)]高(均P<0.05)。重症组中接受免疫强化治疗患者比例和死亡率分别为12/13(12例)和4/13(4例),均高于轻症组[分别为10.8%(4例)和0](均P<0.05)。结论ICIs相关心肌炎发生率虽不高,但重症率、死亡率高,应结合心肌标志物、心电图、超声心动图等手段鉴别重症心肌炎,早诊早治,以改善患者预后。

Objective To analyze the clinical characteristics of patients with severe immune checkpoint inhibitors(ICIs)related myocarditis.Methods A retrospective study was conducted on the 50 patients with ICIs-related myocarditis in the multidisciplinary cardio-oncology clinic of Zhongshan Hospital affiliated to Fudan University from April 2020 to April 2022.The age of patients was(63.7±10.8)years old,including 37 males and 13 females.The patients were divided into the mild group(n=37)and the severe group(n=13)according to severity.The differences of basic characteristics,clinical manifestations,laboratory tests,auxiliary examination,combined irAEs,treatment and outcomes between the two groups of patients were analyzed.Results The immunotherapy time[M(Q_(1),Q_(3))]of patients in the mild group and severe group were 81(49,134)and 24(20,116)days,respectively(P<0.05).In the severe group,the levels of cTnT[0.605(0.317,1.072)μg/L],NT-proBNP[1126(386,1744)ng/L],CK-MB[78(48,238)U/L],and CK-MM[240(45,6543)U/L]were higher than those in the mild group[0.104(0.045,0.189)μg/L,237(39,785)ng/L,24(20,33)U/L,108(72,168)U/L,respectively](all P<0.05).The left ventricular ejection fraction of the severe group[64%(57%,65%)]was lower than that of the mild group[66%(63%,69%)](P<0.05),and the incidence of conduction block(n=4,4/13)and abnormal ventricular wall motion(n=4,4/13),the incidence of ICIs-related myositis(n=10,10/13),ICIs-related hepatitis(n=4,4/13)and ICIs-related neurotoxicity(n=4,4/13)were higher than those in the mild group(n=1,2.7%;n=2,5.4%;n=16,43.2%;n=2,5.4%;n=1,2.7%,respectively)(all P<0.05).The proportion of patients receiving intensified immunosuppressive therapy and mortality rate in the severe group were 12/13(n=12)and 4/13(n=4),which were both higher than those in the mild group[10.8%(n=4)and 0](both P<0.05).Conclusions The incidence of ICIs-related myocarditis is not high,but the severe rate and mortality are high.The differential diagnosis of severe ICIs related myocarditis should be combined with myocardial markers,electrocardiogram and echocardiogram,and early diagnosis and treatment can improve the prognosis of patients.