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Cited by 1,608Cancer Immunotherapy and BiomarkersViral Infections and Immunology ResearchChemotherapy-induced cardiotoxicity and mitigation

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Open access
Mahmood, Syed S., Fradley, Michael G., Cohen, Justine V., Nohria, Anju, Reynolds, Kerry L., Heinzerling, Lucie M., Sullivan, Ryan J., Damrongwatanasuk, Rongras +12 more·2018·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2018.02.037PMC PMC6196725
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Abstract

Background Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. Objectives The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. Methods After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. Results The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. Conclusions Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.

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Crossref · 10.1016/j.jacc.2018.02.037

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  • ICI myocarditis occurs in less than 1% of patients.

    “Despite occurring in &lt;1% of patients”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [45]

    The Results section (PREVALENCE OF MYOCARDITIS; page not provided) reports that 1.14% of 964 ICI-treated patients at Massachusetts General Hospital developed myocarditis. The Discussion likewise describes the overall rate there as just over 1%, contrary to the unqualified claim that it occurs in less than 1% of patients. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • ICI myocarditis has a fatality rate of up to 50%.

    “ICI myocarditis has a high fatality rate of up to 50%.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [45]

    The Results section (Major Adverse Cardiovascular Events; page not provided) reports cardiovascular death in 6 of 35 myocarditis cases, about 17%. The nearly 50% figure refers to a composite of major adverse cardiovascular events, not fatalities. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Recent cases of ICI myocarditis have expanded insights into the role of α-MyHC-specific T cells in myocarditis development.

    “Recent cases of ICI myocarditis have expanded our insights into the role of α -MyHC-specific T cells in myocarditis development. 41-46”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [45]

    The Results (Myocarditis Presentation; page not provided) describe ICI-associated myocarditis cases with T-cell–predominant infiltrates in the heart. They do not identify those cells as α-MyHC-specific or establish their role in myocarditis development, so the mechanistic part of the claim is unsupported by this paper. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • ICI myocarditis is an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination.

    “ICI myocarditis emerges as an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [45]

  • The discovery of α-MyHC-specific T cells in ICI myocarditis suggests potential involvement of autoreactive T cells targeting α-MyHC in the initiation and progression of other forms of myocarditis.

    “This discovery suggests a potential involvement of autoreactive T cells targeting α -MyHC in the initiation and progression of other forms of myocarditis.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [45]

    The Results (Myocarditis Presentation; page unavailable) describe a T-cell–predominant infiltrate in ICI-associated myocarditis. Our copy does not identify α-MyHC-specific T cells or address whether they contribute to the initiation or progression of other forms of myocarditis. Searches for α-MyHC and myosin-heavy-chain autoreactivity found no passage addressing those points. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Cites

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Authors
Mahmood, S. S., Fradley, M. G., Cohen, J. V., Nohria, A., Reynolds, K. L., Heinzerling, L. M., Sullivan, R. J., Damrongwatanasuk, R., Chen, C. L., Gupta, D., Kirchberger, M. C., Awadalla, M., Hassan, M. Z. O., Moslehi, J. J., Shah, S. P., Ganatra, S., Thavendiranathan, P., Lawrence, D. P., Groarke, J. D., & Neilan, T. G.
Affiliations
  • NewYork–Presbyterian Hospital (US)
  • University of South Florida (US)
  • Massachusetts General Hospital (US)
  • Brigham and Women's Hospital (US)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Memorial Sloan Kettering Cancer Center (US)
  • Vanderbilt University Medical Center (US)
  • Lahey Hospital and Medical Center (US)
  • University of Toronto (CA)
  • Harvard University (US)
Corresponding author
Neilan, Tomas G.
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2018-04
Volume
71
Issue
16
Pages
1755-1764
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2018.02.037
PMC
PMC6196725
OpenAlex
W2789315292
Cited by
1,608
References
6
Citations by year
2026: 200 · 2025: 200 · 2024: 211 · 2023: 188 · 2022: 232 · 2021: 200 · 2020: 206 · 2019: 115 · 2018: 53 · 2017: 1
FWCI
53.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Harvard University Center for AIDS Research (P30 AI060354)
  • Sarnoff Cardiovascular Research Foundation
  • National Institutes of Health
  • Kohlberg Foundation
  • National Heart, Lung, and Blood Institute (1R01HL130539-01A1, 1R01HL137562-01A1, K24HL113128-06)
  • Canadian Institutes of Health Research (FRN 147814)
  • American Heart Association (12FTF12060588)
  • National Cancer Institute (P30 CA008748)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
Keywords
immune checkpoint inhibitors, myocarditis, immune-related adverse events, major adverse cardiac events, troponin T, corticosteroid therapy, diabetes mellitus, cancer immunotherapy toxicity, complete heart block
MeSH terms
Antineoplastic Agents, Immunological, Aged, Female, Glucocorticoids, Humans, Male, Methylprednisolone, Middle Aged, Myocarditis, Neoplasms, Registries, Case-Control Studies, Troponin T

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