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Immune checkpoint inhibitor-associated myocarditis: a novel risk score

Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Pr...

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Main Authors: Power, John R. (Author) , Dolladille, Charles (Author) , Ozbay, Benay (Author) , Procureur, Adrien (Author) , Ederhy, Stephane (Author) , Palaskas, Nicolas L (Author) , Lehmann, Lorenz (Author) , Cautela, Jennifer (Author) , Courand, Pierre-Yves (Author) , Hayek, Salim S (Author) , Zhu, Han (Author) , Zaha, Vlad G (Author) , Cheng, Richard K (Author) , Alexandre, Joachim (Author) , Roubille, François (Author) , Baldassarre, Lauren A (Author) , Chen, Yen-Chou (Author) , Baik, Alan H (Author) , Laufer-Perl, Michal (Author) , Tamura, Yuichi (Author) , Asnani, Aarti (Author) , Francis, Sanjeev (Author) , Gaughan, Elizabeth M (Author) , Rainer, Peter P (Author) , Bailly, Guillaume (Author) , Flint, Danette (Author) , Arangalage, Dimitri (Author) , Cariou, Eve (Author) , Florido, Roberta (Author) , Narezkina, Anna (Author) , Liu, Yan (Author) , Sandhu, Shahneen (Author) , Leong, Darryl (Author) , Issa, Nahema (Author) , Piriou, Nicolas (Author) , Heinzerling, Lucie (Author) , Peretto, Giovanni (Author) , Crusz, Shanthini M (Author) , Akhter, Nausheen (Author) , Levenson, Joshua E (Author) , Turker, Isik (Author) , Eslami, Assié (Author) , Fenioux, Charlotte (Author) , Moliner, Pedro (Author) , Obeid, Michel (Author) , Chan, Wei Ting (Author) , Ewer, Stephen M (Author) , Kassaian, Seyed Ebrahim (Author) , Johnson, Douglas B (Author) , Nohria, Anju (Author) , Ben Zadok, Osnat Itzhaki (Author) , Moslehi, Javid J (Author) , Salem, Joe-Elie (Author)
Format: Article (Journal)
Language:English
Published: 18 June 2025
In: European heart journal
Year: 2025, Pages: 1-13
ISSN:1522-9645
DOI:10.1093/eurheartj/ehaf315
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/eurheartj/ehaf315
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Author Notes:John R. Power, Charles Dolladille, Benay Ozbay, Adrien Procureur, Stephane Ederhy, Nicolas L. Palaskas, Lorenz H. Lehmann, Jennifer Cautela, Pierre-Yves Courand, Salim S. Hayek, Han Zhu, Vlad G. Zaha, Richard K. Cheng, Joachim Alexandre, François Roubille, Lauren A. Baldassarre, Yen-Chou Chen, Alan H. Baik, Michal Laufer-Perl, Yuichi Tamura, Aarti Asnani, Sanjeev Francis, Elizabeth M. Gaughan, Peter P. Rainer, Guillaume Bailly, Danette Flint, Dimitri Arangalage, Eve Cariou, Roberta Florido, Anna Narezkina, Yan Liu, Shahneen Sandhu, Darryl Leong, Nahema Issa, Nicolas Piriou, Lucie Heinzerling, Giovanni Peretto, Shanthini M. Crusz, Nausheen Akhter, Joshua E. Levenson, Isik Turker, Assié Eslami, Charlotte Fenioux, Pedro Moliner, Michel Obeid, Wei Ting Chan, Stephen M. Ewer, Seyed Ebrahim Kassaian, Douglas B. Johnson, Anju Nohria, Osnat Itzhaki Ben Zadok, Javid J. Moslehi, and Joe-Elie Salem ; on behalf of International ICI-Myocarditis Registry
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Summary:Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this ‘cardiomyotoxicity’ are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis.A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated.In 748 patients (67% male, age 23-94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5-4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1-3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1-2.6]), and incremental troponin elevation (HR 1.8 [1.4-2.4], 2.9 [1.8-4.7], and 4.6 [2.3-9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events.ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well.NCT04294771 and NCT05454527.
Item Description:Veröffentlicht: 18. Juni 2025
Gesehen am 13.11.2025
Physical Description:Online Resource
ISSN:1522-9645
DOI:10.1093/eurheartj/ehaf315

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