Cardiology Division, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York; Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
Cardio-Oncology Program, H. Lee Moffitt Cancer Center & Research Institute and University of South Florida Division of Cardiovascular Medicine, Tampa, Florida.
J Am Coll Cardiol. 2018 Apr 24;71(16):1755-1764. doi: 10.1016/j.jacc.2018.02.037. Epub 2018 Mar 19.
Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized.
The authors sought to understand the presentation and clinical course of ICI-associated myocarditis.
After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block.
The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates.
Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
心肌炎是免疫检查点抑制剂（ICI）罕见但潜在致命的毒性。ICI 后心肌炎尚未得到很好的描述。
作者旨在了解 ICI 相关性心肌炎的表现和临床过程。
在观察到散发性 ICI 相关性心肌炎病例后，作者创建了一个包含 8 个站点的多中心登记处。从 2013 年 11 月至 2017 年 7 月，共有 35 例 ICI 相关性心肌炎患者，将其与 105 例未发生心肌炎的 ICI 治疗患者的随机样本进行比较。从病历中提取了感兴趣的协变量，包括主要不良心脏事件（MACE）的发生，定义为心血管死亡、心源性休克、心脏骤停和血流动力学显著完全性心脏阻滞的复合事件。
心肌炎的患病率为 1.14%，ICI 开始后中位发病时间为 34 天（四分位距：21 至 75 天）。病例年龄为 65 ± 13 岁，29%为女性，54%无其他免疫相关副作用。与对照组相比，ICI 联合治疗（34%比 2%；p < 0.001）和糖尿病（34%比 13%；p = 0.01）在病例中更为常见。在中位随访 102 天（四分位距：62 至 214 天）期间，16 例（46%）发生 MACE；38%的 MACE 发生时射血分数正常。肌钙蛋白 T 水平≥1.5ng/ml 时，MACE 的风险增加 4 倍（危险比：4.0；95%置信区间：1.5 至 10.9；p = 0.003）。89%的患者接受了类固醇治疗，较低的类固醇剂量与更高的残余肌钙蛋白和更高的 MACE 发生率相关。
ICI 治疗后心肌炎的发生可能比预期更为常见，发生在治疗开始后早期，病程恶性，对高剂量类固醇治疗有反应。
