Braghieri Lorenzo, Gharaibeh Ahmad, Nkashama Lubika, Abushouk Abdelrahman, Abushawer Osama, Mehdizadeh-Shrifi Amir, Honnekeri Bianca, Calabrese Cassandra, Menon Venu, Funchain Pauline, Collier Patrick, Sadler Diego, Moudgil Rohit
Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Department of Internal Medicine, WashU/Barnes-Jewish Hospital, St. Louis, Missouri, USA.
ESC Heart Fail. 2025 Apr;12(2):1237-1245. doi: 10.1002/ehf2.15131. Epub 2024 Oct 31.
Immune checkpoint inhibitors (ICI) are the cornerstone of modern oncology; however, side effects such as ICI-related myocarditis (irM) can be fatal. Recently, Bonaca proposed criteria for irM; however, it is unknown if they correlate well with cardiovascular (CV) ICI-related adverse events. Additionally, whether incident irM portends worse long-term CV outcomes remains unclear. We aimed to determine the incidence of long-term CV comorbidities and CV mortality among irM patients.
The ICI-related adverse event (irAE) registry was queried to identify irM patients by using Bonaca criteria. Random controls were selected after excluding patients with other concomitant irAEs. Patients' demographics, comorbidities and myocarditis presenting features were gathered. Outcomes included 2-year freedom from CV comorbidities (composite of atrial fibrillation, stroke, myocardial infarction and heart failure) and freedom from CV death. IrM was treated as a time-varying covariate.
Seventy-six patients developed irM at a median of 167 days (mean age 69, 63.2% male, 47% lung cancer). Majority of patients had new wall motion abnormalities or EKG changes on presentation. Mean LVEF was 43%, median peak TnT was 0.81, and median NTproBNP was 2057 at irM onset. Two-year freedom from CV comorbidities (67% vs 86.8%, P < 0.001) and death (93.4% vs 99.3%, P = 0.003) was lower among irM patients. Incident irM was an independent predictor of CV death (HR 8.28, P = 0.048), but not CV comorbidities (HR 2.21, P = 0.080).
This is the largest case-control study on irM highlighting worse long-term CV outcomes. Future studies are needed to establish appropriate therapeutic strategies and efficient screening strategies for irM survivors.
免疫检查点抑制剂（ICI）是现代肿瘤学的基石；然而，诸如ICI相关心肌炎（irM）等副作用可能是致命的。最近，博纳卡提出了irM的标准；然而，尚不清楚这些标准是否与心血管（CV）ICI相关不良事件有良好的相关性。此外，新发的irM是否预示着更差的长期心血管结局仍不明确。我们旨在确定irM患者中长期心血管合并症和心血管死亡率的发生率。
通过使用博纳卡标准查询ICI相关不良事件（irAE）登记处来识别irM患者。在排除患有其他伴随irAE的患者后选择随机对照。收集患者的人口统计学、合并症和心肌炎表现特征。结局包括2年无心血管合并症（房颤、中风、心肌梗死和心力衰竭的综合）和无心血管死亡。将irM视为随时间变化的协变量。
76例患者发生irM，中位时间为167天（平均年龄69岁，63.2%为男性，47%为肺癌）。大多数患者在就诊时出现新的室壁运动异常或心电图改变。irM发作时平均左心室射血分数（LVEF）为43%，中位肌钙蛋白T峰值为0.81，中位N末端脑钠肽前体（NTproBNP）为2057。irM患者2年无心血管合并症（67%对86.8%，P<0.001）和无死亡（93.4%对99.3%，P=0.003）的比例较低。新发irM是心血管死亡的独立预测因素（风险比[HR]8.28，P=0.048），但不是心血管合并症的独立预测因素（HR2.21，P=0.080）。
这是关于irM的最大规模病例对照研究，突出了较差的长期心血管结局。未来需要开展研究以建立针对irM幸存者的适当治疗策略和有效的筛查策略。
