Myocarditis in the Setting of Cancer Therapeutics Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology
Myocarditis in the Setting of Cancer Therapeutics Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology
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DOI：
10.1161/circulationaha.118.034497
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发表时间：
2019-07-02
期刊：
影响因子：
37.8
通讯作者：
Moslehi, Javid
中科院分区：
文献类型：
--
作者：
Bonaca, Marc P.;Olenchock, Benjamin A.;Moslehi, Javid
癌症治疗的最新发展改善了结果，但也与心血管并发症有关。利用免疫系统的治疗与称为心肌炎的免疫介导的心肌损伤有关。免疫检查点抑制剂就是这样一种治疗方法，越来越多的病例和队列报告描述了免疫检查点抑制剂相关心肌炎的临床综合征。尽管免疫检查点相关心血管疾病的全谱仍需要完全定义，但所描述的心肌炎病例范围从具有轻度体征和症状的综合征到致命事件。临床环境中的这些观察结果与随机临床试验的结果形成对比，在随机临床试验中，心肌炎是研究者报告的罕见事件，缺乏特定病例定义。与诊断相关的复杂性，以及免疫检查点相关心肌炎的异质性临床表现，使得在临床试验和其他数据集中具有高特异性的心肌炎的确定和识别具有挑战性，限制了更好地了解这些罕见事件的发生率，结局和预测因素的能力。因此，建立一个统一的定义心肌炎的应用在临床试验的癌症免疫治疗将使这些事件有更好的理解。我们提出了一个可操作的定义，癌症治疗相关的心肌炎，可能有助于案件的确定和报告，因此可能会提高这种新的临床综合征的发病率，结果和危险因素的理解。
Recent developments in cancer therapeutics have improved outcomes but have also been associated with cardiovascular complications. Therapies harnessing the immune system have been associated with an immune-mediated myocardial injury described as myocarditis. Immune checkpoint inhibitors are one such therapy with an increasing number of case and cohort reports describing a clinical syndrome of immune checkpoint inhibitor-associated myocarditis. Although the full spectrum of immune checkpoint inhibitor-associated cardiovascular disease still needs to be fully defined, described cases of myocarditis range from syndromes with mild signs and symptoms to fatal events. These observations in the clinical setting stand in contrast to outcomes from randomized clinical trials in which myocarditis is a rare event that is investigator reported and lacking in a specific case definition. The complexities associated with diagnosis, as well as the heterogeneous clinical presentation of immune checkpoint inhibitor-associated myocarditis, have made ascertainment and identification of myocarditis with high specificity challenging in clinical trials and other data sets, limiting the ability to better understand the incidence, outcomes, and predictors of these rare events. Therefore, establishing a uniform definition of myocarditis for application in clinical trials of cancer immunotherapies will enable greater understanding of these events. We propose an operational definition of cancer therapy-associated myocarditis that may facilitate case ascertainment and report and therefore may enhance the understanding of the incidence, outcomes, and risk factors of this novel clinical syndrome.