Division of Cardiology, Cardio-Oncology Program, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, USA.
Division of Cardiology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD, USA.
Cardiovasc Res. 2019 Apr 15;115(5):854-868. doi: 10.1093/cvr/cvz026.
Cardiovascular toxicities associated with immune checkpoint inhibitors (ICIs) have been reported in case series but have been underappreciated due to their recent emergence, difficulties in diagnosis and non-specific clinical manifestations. ICIs are antibodies that block negative regulators of the T cell immune response, including cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and PD-1 ligand (PD-L1). While ICIs have introduced a significant mortality benefit in several cancer types, the augmented immune response has led to a range of immune-related toxicities, including cardiovascular toxicity. ICI-associated myocarditis often presents with arrhythmias, may co-exist with myositis and myasthenia gravis, can be severe, and portends a poor prognosis. In addition, pericardial disease, vasculitis, including temporal arteritis, and non-inflammatory heart failure, have been recently described as immune-related toxicities from ICI. This narrative review describes the epidemiology, diagnosis, pathophysiology, and treatment of cardiovascular toxicities of ICI therapy, highlighting recent developments in the field in the past year.
免疫检查点抑制剂(ICI)相关的心血管毒性已在病例系列中报道,但由于其新近出现、诊断困难和非特异性临床表现,这些毒性一直未被充分认识。ICI 是一种抗体,可阻断 T 细胞免疫反应的负调节剂,包括细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)、程序性细胞死亡蛋白 1(PD-1)和 PD-1 配体(PD-L1)。虽然 ICI 在多种癌症类型中带来了显著的生存获益,但增强的免疫反应导致了一系列免疫相关毒性,包括心血管毒性。ICI 相关性心肌炎常表现为心律失常,可能与肌炎和重症肌无力并存,可能很严重,并预示预后不良。此外,心包疾病、血管炎(包括颞动脉炎)和非炎症性心力衰竭最近被描述为 ICI 的免疫相关毒性。本综述描述了 ICI 治疗的心血管毒性的流行病学、诊断、病理生理学和治疗,强调了过去一年该领域的最新进展。