Immune checkpoint inhibitor-associated myocarditis: A novel risk score

Power JR, Dolladille C, Ozbay B, Procureur A, Ederhy S, Palaskas NL, Lehmann LH, Cautela J, Courand PY, Hayek SS, Zhu H, Zaha VG, Cheng RK, Alexandre J, Roubille F, Baldassarre LA, Chen YC, Baik AH, Laufer-Perl M, Tamura Y, Asnani A, Francis S, Gaughan EM, Rainer PP, Bailly G, Flint D, Arangalage D, Cariou E, Florido R, Narezkina A, Liu Y, Sandhu S, Leong D, Issa N, Piriou N, Heinzerling L, Peretto G, Crusz SM, Akhter N, Levenson JE, Turker I, Eslami A, Fenioux C, Moliner P, Obeid M, Chan WT, Ewer SM, Kassaian SE, Johnson DB, Nohria A, Ben Zadok OI, Moslehi JJ, Salem JE, Deswal A, Thuny F, Bouali A, Hughes A, Moser L, Faure M, Vila RB, Jimenez J, Paven E, Galli E, Lopez Fernandez T, Cobarro L, Habib M, Tajiri K, Rocher F, Bejan-Angoulvant T, Bilen MA, Parashar S, Guha A, Song W, Koenig D, Mertz K, Lenneman C, Haydon A, Lesiuk C, Tresorier R, Samara Y, Grohe C, Dietrich PY, Tierney S, Rassy E, Mervoyer E, Suzuki S, Fukushima S, Robert-Halabi M, Morimoto R, Copeland-Halperin R, Layoun M, Wang J, Fernando S, Rota E, Katsume Y, Kiniwa Y, Warner E, Seki N, Ruf T, Delaune J, Aghel N (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 47

Pages Range: 1050-1062

Journal Issue: 9

DOI: 10.1093/eurheartj/ehaf315

Abstract

Background and Aims 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. Methods 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. Results 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. Conclusions 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.

Involved external institutions

University of Washington United States (USA) (US) Normandy University / Normandie Université France (FR) Centre Hospitalier Universitaire de Montpellier (CHU/CHRU MTP) France (FR) Yale University United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) Tel Aviv University Israel (IL) IUHW International University of Health and Welfare Mita Hospital / 国際医療福祉大学三田病院 Japan (JP) Beth Israel Deaconess Medical Center (BIDMC) United States (USA) (US) Maine Medical Center (MMC) United States (USA) (US) Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal France (FR) University of Virginia (UVA) United States (USA) (US) Medizinische Universität Graz Austria (AT) Dartmouth-Hitchcock Medical Center (DHMC) United States (USA) (US) Stanford University United States (USA) (US) Hôpital Bichat-Claude-Bernard (CHU, APHP) France (FR) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Barts Health NHS Trust United Kingdom (GB) Hôpital Rangueil France (FR) Northwestern University United States (USA) (US) University of Utah United States (USA) (US) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) University of Texas at Austin United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) McMaster University Canada (CA) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) France (FR) Klinikum der Universität München (LMU Klinikum) Germany (DE) Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation) Italy (IT) Georges Pompidou European Hospital / Hôpital Européen Georges-Pompidou (HEGP) France (FR) Centre hospitalier universitaire Henri-Mondor (CHU Henri-Mondor) France (FR) Bellvitge Biomedical Research Institute (IDIBELL) Spain (ES) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH) Chi Mei Medical Center Taiwan (TW) University of Wisconsin - Madison United States (USA) (US) MedStar Washington Hospital Center United States (USA) (US) Vanderbilt University United States (USA) (US) Mass General Brigham United States (USA) (US) Pitié-Salpêtrière University Hospital / Hôpital universitaire Pitié-Salpêtrière France (FR) University of Pittsburgh Medical Center (UPMC) United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Universitätsklinikum Heidelberg Germany (DE) Aix-Marseille University / Aix-Marseille Université France (FR) Université Claude Bernard Lyon 1 (UCB) France (FR) University of Michigan United States (USA) (US)

How to cite

APA:

Power, J.R., Dolladille, C., Ozbay, B., Procureur, A., Ederhy, S., Palaskas, N.L.,... Aghel, N. (2026). Immune checkpoint inhibitor-associated myocarditis: A novel risk score. European Heart Journal, 47(9), 1050-1062. https://doi.org/10.1093/eurheartj/ehaf315

MLA:

Power, John R., et al. "Immune checkpoint inhibitor-associated myocarditis: A novel risk score." European Heart Journal 47.9 (2026): 1050-1062.

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