Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction

International ICI-Myocarditis Registry

doi:10.1016/j.jaccao.2025.01.020

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction

International ICI-Myocarditis Registry

Cardiology

University of California at San Francisco
Taipei Medical University
Caen University Medical School
Normandie Université
Sorbonne Université
University of Texas Southwestern Medical Center
Northwestern University
University of Texas MD Anderson Cancer Center
Heidelberg University
German Centre for Cardiovascular Research
German Cancer Research Center
Hôpital Nord AP-HM
Hôpital de la Croix-Rousse
Universite Claude Bernard Lyon 1
University of Michigan, Ann Arbor
Stanford University
University of Washington
Yale University
Université de Montpellier
Beth Israel Deaconess Medical Center
International University of Health and Welfare
Maine Medical Center
University of Virginia
Vanderbilt University
Dartmouth College
Medical University of Graz
BioTechMed-Graz
St. Johann in Tirol General Hospital
Université Paris Cité
University of Wisconsin-Madison
CHU de Toulouse
Johns Hopkins University
IRCCS San Raffaele Scientific Institute
Rabin Medical Center Israel
University of California at San Diego
University of Pittsburgh
University of Texas at Austin
Barts Health NHS Trust
Bordeaux University Hospital
University Hospital
McMaster University
Peter Maccallum Cancer Centre
Washington University St. Louis
Hospital Universitari de Bellvitge
University of Lausanne
Ludwig Maximilian University of Munich
Chi-Mei Medical Center
University of Texas at Dallas

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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/m², 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.

Original language	English
Pages (from-to)	234-248
Number of pages	15
Journal	JACC: CardioOncology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.jaccao.2025.01.020
State	Published - Apr 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cardiac magnetic resonance
echocardiography
heart failure
immune checkpoint inhibitor myocarditis
immunotherapy
left ventricular ejection fraction
myocarditis
troponin

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10.1016/j.jaccao.2025.01.020

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@article{6a7a376a47a2477590a6456d615a6dbf,

title = "Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction",

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/m2, 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.",

keywords = "cardiac magnetic resonance, echocardiography, heart failure, immune checkpoint inhibitor myocarditis, immunotherapy, left ventricular ejection fraction, myocarditis, troponin",

author = "\{International ICI-Myocarditis Registry\} and Chen, \{Yen Chou\} and Charles Dolladille and Anjali Rao and Palaskas, \{Nicolas L.\} and Anita Deswal and Lorenz Lehmann and Jennifer Cautela and Courand, \{Pierre Yves\} and Salim Hayek and Han Zhu and Cheng, \{Richard K.\} and Joachim Alexandre and Baldassarre, \{Lauren A.\} and Fran{\c c}ois Roubille and Michal Laufer-Perl and Aarti Asnani and Stephane Ederhy and Yuichi Tamura and Sanjeev Francis and Gaughan, \{Elizabeth M.\} and Johnson, \{Douglas B.\} and Flint, \{Danette L.\} and Rainer, \{Peter P.\} and Guillaume Bailly and Ewer, \{Steven M.\} and Aras, \{Mandar A.\} and Dimitri Arangalage and Eve Cariou and Roberta Florido and Giovanni Peretto and \{Itzhaki Ben Zadok\}, Osnat and Nausheen Akhter and Anna Narezkina and Levenson, \{Joshua E.\} and Yan Liu and Crusz, \{Shanthini M.\} and Nahema Issa and Nicolas Piriou and Darryl Leong and Shahneen Sandhu and Isik Turker and Pedro Moliner and Michel Obeid and Lucie Heinzerling and Chang, \{Wei Ting\} and Andrew Stewart and Vishnu Venkatesh and Zoe Du and Anirudh Yadavalli and Dohyeong Kim",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = apr,

doi = "10.1016/j.jaccao.2025.01.020",

language = "אנגלית",

volume = "7",

pages = "234--248",

journal = "JACC: CardioOncology",

issn = "2666-0873",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction

AU - International ICI-Myocarditis Registry

AU - Chen, Yen Chou

AU - Dolladille, Charles

AU - Rao, Anjali

AU - Palaskas, Nicolas L.

AU - Deswal, Anita

AU - Lehmann, Lorenz

AU - Cautela, Jennifer

AU - Courand, Pierre Yves

AU - Hayek, Salim

AU - Zhu, Han

AU - Cheng, Richard K.

AU - Alexandre, Joachim

AU - Baldassarre, Lauren A.

AU - Roubille, François

AU - Laufer-Perl, Michal

AU - Asnani, Aarti

AU - Ederhy, Stephane

AU - Tamura, Yuichi

AU - Francis, Sanjeev

AU - Gaughan, Elizabeth M.

AU - Johnson, Douglas B.

AU - Flint, Danette L.

AU - Rainer, Peter P.

AU - Bailly, Guillaume

AU - Ewer, Steven M.

AU - Aras, Mandar A.

AU - Arangalage, Dimitri

AU - Cariou, Eve

AU - Florido, Roberta

AU - Peretto, Giovanni

AU - Itzhaki Ben Zadok, Osnat

AU - Akhter, Nausheen

AU - Narezkina, Anna

AU - Levenson, Joshua E.

AU - Liu, Yan

AU - Crusz, Shanthini M.

AU - Issa, Nahema

AU - Piriou, Nicolas

AU - Leong, Darryl

AU - Sandhu, Shahneen

AU - Turker, Isik

AU - Moliner, Pedro

AU - Obeid, Michel

AU - Heinzerling, Lucie

AU - Chang, Wei Ting

AU - Stewart, Andrew

AU - Venkatesh, Vishnu

AU - Du, Zoe

AU - Yadavalli, Anirudh

AU - Kim, Dohyeong

PY - 2025/4

Y1 - 2025/4

N2 - 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/m2, 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.

AB - 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/m2, 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.

KW - cardiac magnetic resonance

KW - echocardiography

KW - heart failure

KW - immune checkpoint inhibitor myocarditis

KW - immunotherapy

KW - left ventricular ejection fraction

KW - myocarditis

KW - troponin

UR - https://www.scopus.com/pages/publications/105001824990

U2 - 10.1016/j.jaccao.2025.01.020

DO - 10.1016/j.jaccao.2025.01.020

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 40246381

AN - SCOPUS:105001824990

SN - 2666-0873

VL - 7

SP - 234

EP - 248

JO - JACC: CardioOncology

JF - JACC: CardioOncology

IS - 3

ER -

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction

Abstract

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Keywords

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