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免疫检查点抑制剂相关心脏不良反应的诊治进展及管理策略

Management of cardiac adverse events related to immune checkpoint inhibitors

  • 摘要: 免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)给肿瘤治疗带来了翻天覆地的变化,标志着免疫治疗新时代的开启。与此同时,免疫治疗相关不良反应报道也日趋增多。免疫相关心脏不良反应虽发生率较低,但病死率极高,严重影响肿瘤患者临床转归。患者可表现为乏力、气促、胸痛、心悸等症状。实验室指标可见肌钙蛋白、氨基末端脑钠肽前体(NT-proBNP)等升高。心电图显示可有新发的传导阻滞。心脏核磁共振(cardiac magnetic resonance,CMR)显示心肌炎表现。约半数患者超声心动图示左室射血分数 < 50%。心内膜心肌活检作为诊断的金标准,常见组织学表现为以T细胞为主的淋巴细胞浸润。治疗上以早期应用足量激素为主,可酌情使用英夫利昔单抗、免疫球蛋白等免疫抑制剂。对使用ICIs的所有患者,尤其是伴有糖尿病病史、自身免疫性疾病病史或联合治疗的患者,用药早期建议严密监测心悸、气促、乏力等症状以及肌钙蛋白、NT-proBNP等指标。

     

    Abstract: Immune checkpoint inhibitors (ICIs) have greatly improved clinical outcomes in multiple cancer types and are regarded as a new beginning of cancer immunotherapy. However, high-grade immune-related adverse events can occur. Cardiotoxic effects are not common, but are often serious complications with a relatively high mortality. Patients may have symptoms of fatigue, shortness of breath, chest pain, and palpitation. The laboratory indexes showed the increase of troponin and N-terminal B-type natriuretic peptide (NT-proBNP). The electrocardiogram shows that there may be a new conduction block. Cardiac magnetic resonance (CMR) shows myocarditis, and about half of the patients show left ventricular ejection fraction less than 50% by echocardiography. Endocardial biopsy is the gold standard for diagnosis, and the common histological manifestation is lymphocyte infiltration dominated by T cells. Early use of sufficient steroids is the main treatment, and immune-suppressants such as infliximab and immunoglobulin can be used as appropriate.For all patients using ICIs, especially those with a history of diabetes, autoimmune disease or combined treatment, it is recommended to closely monitor the symptoms such as palpitation, shortness of breath, fatigue and troponin, NT-proBNP and other indexes in the early stage of treatment.

     

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