免疫检查点抑制剂所致不良心血管事件的临床特点分析

Clinical Characteristics of Immune Checkpoint Inhibitors Associated Adverse Cardiovascular Events

目的:分析免疫检查点抑制剂(ICIs)所致不良心血管事件的临床特点及转归。方法:通过病案系统检索2018年1月至2021年11月我院诊断ICIs所致心肌炎患者,回顾性分析患者的临床特点、治疗及转归。结果:共检索出ICIs所致心肌炎患者4例。4例患者均应用程序性细胞死亡蛋白1(PD-1)抑制剂,其中1例患者联合应用PD-1抑制剂和T细胞免疫球蛋白/免疫受体酪氨酸抑制基序结构域蛋白(TIGIT)单抗。应用ICIs后发病时间为17~27 d。4例患者3例为女性,年龄范围46~83岁。2例患者合并心力衰竭;3例患者合并不同程度的心律失常;1例患者合并少量心包积液;无患者出现严重心脏瓣膜病变。除心肌炎外,4例均合并肝损伤;3例合并肌损伤。除1例较轻患者未予特殊治疗外,3例患者均应用糖皮质激素,其中1例联用静脉注射丙种球蛋白(IVIG)。3例患者治疗后明显好转,1例患者(联合应用PD-1抑制剂+TIGIT单抗,给予糖皮质激素+IVIG治疗)因持续性室性心动过速+心原性休克死亡。结论:ICIs所致心肌炎常表现为心律失常及心功能衰竭,多易合并肝损伤及肌损伤,应根据心肌炎病情程度及时给予糖皮质激素,甚至IVIG治疗,但重症患者仍预后较差。

Objectives:To analyze the clinical characteristics of immune checkpoint inhibitors(ICIs)-associated adverse cardiovascular events.Methods:Patients who were diagnosed with ICIs-associated myocarditis from January 2018 to November 2021 were screened via HAITAI Electronic Medical Record System.The patients'clinical characteristics,treatment and prognosis were analyzed retrospectively.Results:Four patients with ICIs-associated myocarditis were identified,all of whom received programmed cell death protein-1(PD-1)inhibitors.One of them received PD-1 inhibitor combined with T cell immunoglobulin and ITIM domain(TIGIT)monoclonal antibody.The time to presentation of symptoms from receiving therapy ranged from 17-27 days.Three patients were female.The age of the patients ranged from 46-83 years old.Two patients developed heart failure and three patients developed arrhythmias.All patients had liver dysfunction,and three patients had muscular injury.Three patients received steroids treatment and one patient was treated with steroids combined with intravenous immunoglobulin(IVIG).One asymptomatic patient did not receive special therapy for ICIs.Three patients improved well post therapy.One patient,who received PD-1 inhibitor combined with TIGIT monoclonal antibody,died of sustained ventricular tachyarrhythmia and cardiac shock.Conclusions:Patients with ICIs-associated myocarditis often suffer from arrhythmia and heart failure combined with liver injury and muscular injury.Steroids could be administered as first line therapy for most patients with moderate-to-severe symptoms.IVIG therapy could be started as second line therapy immediately following steroid treatment failure.However,the prognosis of patients with severe ICIs-associated myocarditis is still poor.