免疫检查点抑制剂相关性心肌炎与左心室收缩功能障碍

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction.

作者信息

Chen Yen-Chou, Dolladille Charles, Rao Anjali, Palaskas Nicolas L, Deswal Anita, Lehmann Lorenz, Cautela Jennifer, Courand Pierre-Yves, Hayek Salim, Zhu Han, Cheng Richard K, Alexandre Joachim, Baldassarre Lauren A, Roubille François, Laufer-Perl Michal, Asnani Aarti, Ederhy Stephane, Tamura Yuichi, Francis Sanjeev, Gaughan Elizabeth M, Johnson Douglas B, Flint Danette L, Rainer Peter P, Bailly Guillaume, Ewer Steven M, Aras Mandar A, Arangalage Dimitri, Cariou Eve, Florido Roberta, Peretto Giovanni, Itzhaki Ben Zadok Osnat, Akhter Nausheen, Narezkina Anna, Levenson Joshua E, Liu Yan, Crusz Shanthini M, Issa Nahema, Piriou Nicolas, Leong Darryl, Sandhu Shahneen, Turker Isik, Moliner Pedro, Obeid Michel, Heinzerling Lucie, Chang Wei-Ting, Stewart Andrew, Venkatesh Vishnu, Du Zoe, Yadavalli Anirudh, Kim Dohyeong, Chandra Alvin, Zhang Kathleen W, Power John R, Moslehi Javid, Salem Joe-Elie, Zaha Vlad G

机构信息

Division of Cardiology, University of California-San Francisco, San Francisco, California, USA; Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.

Normandie Université, UNICAEN, INSERM U1086 ANTICIPE, Caen, France; Caen-Normandy University Hospital, PICARO Cardio-Oncology Program, Department of Pharmacology, Caen, France; Department of Pharmacology, Sorbonne University, INSERM, CIC-1901, Hôpital Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

出版信息

JACC CardioOncol. 2025 Apr;7(3):234-248. doi: 10.1016/j.jaccao.2025.01.020.

DOI:10.1016/j.jaccao.2025.01.020

PMID:40246381

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12046861/

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.

OBJECTIVES

The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M. A secondary objective was to evaluate the relationship between LVEF and 30-day all-cause mortality.

METHODS

The International ICI-Myocarditis Registry, a retrospective, international, multicenter database, included 757 patients hospitalized with ICI-M. Patients were stratified by LVEF as reduced LVEF (<50%) or preserved LVEF (≥50%) on admission. Cox proportional hazards models were used to assess the associations between LVEF and clinical events, and multivariable logistic regression was conducted to examine factors linked to LVEF.

RESULTS

Of 757 patients, 707 had documented LVEFs on admission: 244 (35%) with LVEF <50% and 463 (65%) with LVEF ≥50%. Compared with patients with LVEF ≥50%, those with LVEF <50% were younger (<70 years), had a body mass index of <25 kg/m, and were more likely to have received chest radiation (24.2% vs 13.5%; P < 0.001). Multivariable analysis identified predictors of LVEF <50%, including exposure to v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated protein kinase inhibitors, pre-existing heart failure, dyspnea at presentation, and at least 40 days from ICI initiation to ICI-M onset. Conversely, myositis symptoms were associated with LVEF ≥50%. LVEF <50% was marginally associated with 30-day all-cause mortality (unadjusted log-rank P = 0.062; adjusted for age, cancer types, and ICI therapy, HR: 1.50; 95% CI: 1.02-2.20).

CONCLUSIONS

Dyspnea, time from ICI initiation, a history of heart failure, and prior cardiotoxic therapy may be predictors of an initial LVEF <50% in patients with ICI-M.

摘要

背景

免疫检查点抑制剂（ICIs）改变了癌症治疗方式，但ICI相关性心肌炎（ICI-M）仍然是一种潜在的致命并发症。ICI-M患者左心室射血分数（LVEF）<50%的临床意义及预测因素尚不清楚。

目的

本研究旨在确定ICI-M住院时LVEF<50%与≥50%相关的因素。次要目的是评估LVEF与30天全因死亡率之间的关系。

方法

国际ICI相关性心肌炎注册研究是一个回顾性、国际性、多中心数据库，纳入了757例因ICI-M住院的患者。根据入院时LVEF将患者分为LVEF降低组（<50%）和LVEF保留组（≥50%）。采用Cox比例风险模型评估LVEF与临床事件之间的关联，并进行多变量逻辑回归分析以检查与LVEF相关的因素。

结果

757例患者中，707例入院时有记录的LVEF：244例（35%）LVEF<50%，463例（65%）LVEF≥50%。与LVEF≥50%的患者相比，LVEF<50%的患者更年轻（<70岁），体重指数<25kg/m²，且更有可能接受过胸部放疗（24.2%对13.5%；P<0.001）。多变量分析确定了LVEF<50%的预测因素，包括暴露于v-raf鼠肉瘤病毒癌基因同源物B1/丝裂原活化蛋白激酶抑制剂、既往心力衰竭、就诊时呼吸困难以及从ICI开始至ICI-M发病至少40天。相反，肌炎症状与LVEF≥50%相关。LVEF<50%与30天全因死亡率存在边缘关联（未调整的对数秩检验P=0.062；经年龄、癌症类型和ICI治疗调整后，HR：1.50；95%CI：1.02-2.20）。