背景：免疫检查点抑制剂（ICIs）可以诱导心血管毒性。
目的：前瞻性评估实体癌患者ICIs主要心血管事件（MACE）的发生率：心肌炎，心包炎,急性冠脉综合征,心力衰竭,高度传导异常或持续性室性心律失常，或6周时心血管死亡（早期MACE），包括由独立裁决委员会使用当前推荐的诊断标准进行的无症状临床改变.次要目标是在6个月（晚期MACE）时增加房颤（AF）的上述事件的发生率。
结果：参与者接受了预ICIs和重复的多模态心脏成像（超声心动图，心脏磁共振（CMR），血清生物标志物（超敏肌钙蛋白I），和6周和6个月时的节律监测（动态心电图监测）。纳入49例患者（男性38例（77.6%）；平均年龄64.3（SD11.0）岁）（2020年6月至2021年12月）。在平均40.1天（SD5.9天）的9例（18.4％）患者中观察到早期MACE，心力衰竭（HF）在5（10.2％），室性心律失常,或4例（8.2％）患者出现新的传导障碍。房颤病史（HR4.49（CI1.11-18.14），P=0.035)预测早期MACE。随访6个月时,在15/49（31％）患者中观察到18次MACE，有6例（12.2%）HF事件，5（10.2％）明显的室性心律失常，或者传导障碍，和4（8.2％）AF。无MACE（P=0.003）或HF（P=0.0028）的患者LVEF明显下降（P<0.001）。纳入时肌酐较高（HR0.99[0.98-1.00]，P=0.006）在多变量分析中预测HF。在我们的研究队列中，重复CMR没有明显的T1或T2映射变化。
结论：使用彻底的检测策略时，ICIs的心脏毒性比以前描述的更频繁，主要包括HF和无症状性节律紊乱。
BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities.
OBJECTIVE: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE).
RESULTS: Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6 weeks and 6 months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6 months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR.
CONCLUSIONS: Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.
