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Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

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机构: [1]Tianjin Med Univ, Hosp 2, Tianjin Inst Cardiol, Dept Cardiol,Tianjin Key Lab Ion Mol Funct Cardiov, 23 Pingjiang Rd, Tianjin 300211, Peoples R China [2]Tianjin Huanghe Hosp, Dept Oncol, Tianjin 300110, Peoples R China [3]China Japan Friendship Hosp, Dept Cardiol, Beijing, Peoples R China [4]Hebei Med Univ, Hosp 4, Dept Funct, Shijiazhuang, Hebei, Peoples R China [5]Cardiovasc Analyt Grp, Cardiooncol Res Unit, Hong Kong, Peoples R China [6]Hong Kong Metropolitan Univ, Sch Nursing & Hlth Studies, Hong Kong, Peoples R China [7]PowerHealth Ltd, Cardiovasc Analyt Grp, Cardiac Electrophysiol Unit, Hong Kong, Peoples R China
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关键词: cardiac troponin-I cardiovascular adverse events creatine kinase isoenzyme-MB immune checkpoint inhibitor myocarditis neutrophil to lymphocyte ratio

摘要:
Background: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Methods: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. Results: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). Conclusions: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

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大类 | 3 区 医学
小类 | 3 区 肿瘤学
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大类 | 3 区 医学
小类 | 3 区 肿瘤学
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Q2 ONCOLOGY

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第一作者机构: [1]Tianjin Med Univ, Hosp 2, Tianjin Inst Cardiol, Dept Cardiol,Tianjin Key Lab Ion Mol Funct Cardiov, 23 Pingjiang Rd, Tianjin 300211, Peoples R China
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