Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction

被引：1

作者：

Chen, Yen-Chou ^{[1
,2
,3
,4
]}

Dolladille, Charles ^{[5
,6
,7
]}

Rao, Anjali ^{[8
,9
]}

Palaskas, Nicolas L. ^{[10
]}

Deswal, Anita ^{[10
]}

Lehmann, Lorenz ^{[11
,12
,13
]}

Cautela, Jennifer ^{[14
]}

Courand, Pierre-Yves ^{[15
,16
,17
]}

Hayek, Salim ^{[18
]}

Zhu, Han ^{[19
,20
]}

Cheng, Richard K. ^{[21
]}

Alexandre, Joachim ^{[5
,6
]}

Baldassarre, Lauren A. ^{[22
]}

Roubille, Francois ^{[23
]}

Laufer-Perl, Michal ^{[24
]}

Asnani, Aarti ^{[25
]}

Ederhy, Stephane ^{[26
]}

Tamura, Yuichi ^{[27
]}

Francis, Sanjeev ^{[28
]}

Gaughan, Elizabeth M. ^{[29
]}

Johnson, Douglas B. ^{[30
]}

Flint, Danette L. ^{[31
]}

Rainer, Peter P. ^{[32
,33
,34
]}

Bailly, Guillaume ^{[35
]}

Ewer, Steven M. ^{[36
]}

Aras, Mandar A. ^{[1
]}

Arangalage, Dimitri ^{[37
,38
,39
]}

Cariou, Eve ^{[40
]}

Florido, Roberta ^{[41
]}

Peretto, Giovanni ^{[42
]}

Zadok, Osnat Itzhaki Ben ^{[43
]}

Akhter, Nausheen ^{[44
]}

Narezkina, Anna ^{[45
]}

Levenson, Joshua E. ^{[46
]}

Liu, Yan ^{[47
]}

Crusz, Shanthini M. ^{[48
]}

Issa, Nahema ^{[49
]}

Piriou, Nicolas ^{[50
]}

Leong, Darryl ^{[51
]}

Sandhu, Shahneen ^{[52
]}

Turker, Isik ^{[53
]}

Moliner, Pedro ^{[54
]}

Obeid, Michel ^{[55
]}

Heinzerling, Lucie ^{[56
]}

Chang, Wei-Ting ^{[57
]}

Stewart, Andrew ^{[8
]}

Venkatesh, Vishnu ^{[8
]}

Du, Zoe

Yadavalli, Anirudh ^{[58
]}

Kim, Dohyeong ^{[58
]}

机构：

[1] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA

[2] Taipei Med Univ Hosp, Div Cardiol, Taipei, Taiwan

[3] Taipei Med Univ Hosp, Cardiovasc Res Ctr, Taipei, Taiwan

[4] Taipei Med Univ, Taipei Heart Inst, Taipei, Taiwan

[5] Normandie Univ, UNICAEN, INSERM U1086, ANTICIPE, Caen, France

[6] Caen Normandy Univ Hosp, Dept Pharmacol, PICARO Cardiooncol Program, Caen, France

[7] Sorbonne Univ, Hop Pitie Salpetriere, Assistance Publ Hop Paris, Dept Pharmacol,INSERM,CIC 190, Paris, France

[8] Univ Texas SouthWestern Med Ctr, Dept Internal Med, Div Cardiol, Dallas, TX USA

[9] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Houston, TX USA

[11] Univ Hosp Heidelberg, Dept Cardiol Angiol & Pneumol, Heidelberg, Germany

[12] German Ctr Cardiovasc Res, Partner Site Heidelberg Mannheim, Mannheim, Germany

[13] German Canc Res Ctr, Heidelberg, Germany

[14] Aix Marseille Univ, Nord Hosp, Assistance Publ Hop Marseille, Dept Cardiol,Univ Mediterranean Ctr CardioOncol, Marseille, France

[15] Hop Croix Rousse, Federat Cardiol, Hosp Civils Lyon, Lyon, France

[16] Hosp Civils Lyon, Hop Lyon Sud, Lyon, France

[17] Univ Lyon, Univ Claude Bernard, Lyon, France

[18] Univ Michigan, Dept Cardiol, Ann Arbor, MI USA

[19] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA USA

[20] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA USA

[21] Univ Washington, Div Cardiol, Seattle, WA USA

[22] Yale Univ, Dept Cardiol, New Haven, CT USA

[23] Univ Montpellier, Dept Cardiol, INI CRT,CNRS, CHU Montpellier,PhyMedExp,Inserm, Montpellier, France

[24] Tel Aviv Univ, Fac Med, Tel Aviv Sourasky Med Ctr, Dept Cardiol, Tel Aviv, Israel

[25] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA

[26] Hosp St Antoine, Assistance Publ Hop Paris, Cardiol Dept, Paris, France

[27] Int Univ Hlth & Welf, Mita Hosp, Cardiovasc Ctr, Tokyo, Japan

[28] Maine Med Ctr, Cardiovasc Serv Line, Portland, ME USA

[29] Univ Virginia, Div Hematol Oncol, Charlottesville, VA USA

[30] Vanderbilt Univ, Div Hematol & Oncol, Nashville, TN USA

[31] Dartmouth Hitchcock Med Ctr, Heart & Vasc Ctr, Lebanon, NH USA

[32] Med Univ Graz, Div Cardiol, Graz, Austria

[33] BioTechMed Graz, Graz, Austria

[34] St Johann In Tirol Gen Hosp, St Johann In Tirol, Austria

[35] Hop Lariboisiere, Assistance Publ Hop Paris, Paris, France

[36] Univ Wisconsin, Sch Med & Publ Hlth, Div Cardiovasc Med, Madison, WI USA

[37] Hop Xavier Bichat, Assistance Publ Hop Paris, Dept Cardiol, Paris, France

[38] Univ Paris, UMRS1148, INSERM, Paris, France

[39] Univ Paris, Paris, France

[40] Rangueil Univ Hosp, Dept Cardiol, Toulouse, France

[41] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA

[42] IRCCS San Raffaele Sci Inst, Dis Unit Myocarditis & Arrhythmogen Cardiomyopathi, Milan, Italy

[43] Rabin Med Ctr, Cardiol Dept, Petah Tiqwa, Israel

[44] Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, Chicago, IL USA

[45] Univ Calif San Diego, Div Cardiovasc Med, San Diego, CA USA

[46] Univ Pittsburgh, Med Ctr, Heart & Vasc Inst, Pittsburgh, PA USA

[47] Univ Texas Austin, Dell Med Sch, Dept Internal Med, Div Cardiol, Austin, TX USA

[48] Univ Coll London Hosp, Barts Hlth NHS Trust, London, England

[49] Bordeaux Univ Hosp, Bordeaux, France

[50] Nantes Univ, Inst Thorax, Ctr Reference Cardiomyopathies, CHU Nantes, Nantes, France

来源：

JACC: CARDIOONCOLOGY | 2025年 / 7卷 / 03期

基金：

奥地利科学基金会; 美国国家卫生研究院;

关键词：

cardiac magnetic resonance; echocardiography; heart failure; immune checkpoint inhibitor myocarditis; immunotherapy; left ventricular ejection fraction; myocarditis; tropon in; MAGNETIC-RESONANCE; CARDIAC EVENTS;

D O I：

10.1016/j.jaccao.2025.01.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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(2), and were more likely to have received chest radiation (24.2% vs 13.5%; P < 0.001). Multi-variable 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 1/4 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. (JACC CardioOncol. 2025;7:234-248) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：234 / 248

页数：137

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