{
  "abstract": "Background: Immune checkpoint inhibitor (ICI) myocarditis typically develops soon after treatment initiation (<90 days) but may also occur as a delayed complication after discontinuation of ICI therapy. The clinical and histopathologic differences between early- and late-manifestation ICI myocarditis remain unclear.\n\nObjectives: This study sought to compare the clinical features and myocardial histopathology of early- versus late-manifestation ICI myocarditis.\n\nMethods: We conducted a retrospective national cohort study of patients diagnosed with myocarditis after ICI initiation who underwent endomyocardial biopsy. Biopsy samples were analyzed for inflammatory cell infiltration, severity of myocardial inflammation, and collagen volume fraction.\n\nResults: Among 35 patients (mean age: 66 ± 13 years; 71.4% male), 26 (74.3%) developed early-manifestation myocarditis (<90 days), whereas 9 (25.7%) had late-manifestation myocarditis (≥90 days). Early-manifestation cases showed significantly more severe myocardial inflammation; higher levels (median [Q1-Q3]) of CD3+ T cells (432 [173-1,381] vs 121 [43-400] cells/mm2; P = 0.036), CD8+ T cells (289 [73-994] vs 86 [21-168] cells/mm2; P = 0.019), and CD 68+ macrophages (307 [116-841] vs 57 [36-200] cells/mm2; P = 0.008); and higher CD4+ T-cell levels that did not reach statistical significance (P = 0.054). There were no significant differences in regulatory T cells or collagen volume. Clinically, early-manifestation myocarditis was characterized by higher cardiac biomarker levels and older age, whereas left ventricular ejection fraction was similar between groups. Mortality due to myocarditis occurred in 2 early-manifestation cases and in no late-manifestation cases. Conversely, cancer-related mortality was more frequent in the late-manifestation group (n = 3) than in the early-manifestation group (n = 2). ICI therapy was reinitiated in only 2 patients overall.\n\nConclusions: Late-manifestation ICI myocarditis may represent a temporally distinct or partially attenuated inflammatory phase. Despite a milder inflammatory profile, higher cancer-related mortality was observed, suggesting that cautious ICI reinitiation may warrant consideration in selected patients within this subgroup.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Japan",
    "Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan",
    "Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan",
    "Department of Cardiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan",
    "Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan",
    "Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan",
    "The Second Department of Internal Medicine, University of Toyama, Toyama, Japan",
    "Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan",
    "Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Hemo-Vascular Advanced Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan",
    "Department of Cardiology, Toyama Prefectural Central Hospital, Toyama, Japan",
    "Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine Kagawa University, Kagawa, Japan",
    "Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan",
    "Department of Cardiology, National Center for Global Health and Medicine, Tokyo, Japan",
    "International University of Health and Welfare School of Medicine, Tokyo, Japan",
    "Department of Frontier Cardiovascular Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kazuaki Maruyama"
    },
    {
      "affs": [
        1
      ],
      "name": "Yudai Tamura"
    },
    {
      "affs": [
        2
      ],
      "name": "Shiro Nakamori"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Kazuko Tajiri"
    },
    {
      "affs": [
        5
      ],
      "name": "Hirofumi Tomita"
    },
    {
      "affs": [
        6
      ],
      "name": "Koichiro Kinugawa"
    },
    {
      "affs": [
        7
      ],
      "name": "Ryota Morimoto"
    },
    {
      "affs": [
        8
      ],
      "name": "Hiroshi Akazawa"
    },
    {
      "affs": [
        9
      ],
      "name": "Toshihiro Tsuruda"
    },
    {
      "affs": [
        10
      ],
      "name": "Michiro Maruyama"
    },
    {
      "affs": [
        11
      ],
      "name": "Yuichi Miyake"
    },
    {
      "affs": [
        12
      ],
      "name": "Hiroaki Kawano"
    },
    {
      "affs": [
        0,
        13
      ],
      "name": "Michiaki Hiroe"
    },
    {
      "affs": [
        2
      ],
      "name": "Kaoru Dohi"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kyoko Imanaka-Yoshida"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Issei Komuro"
    },
    {
      "affs": [
        1,
        14
      ],
      "name": "Yuichi Tamura"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5jgkw1za8xcn8.bib",
  "cited_by": 1,
  "doi": "10.1016/j.jaccao.2026.07.008",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13699032/",
  "id": "5jgkw1za8xcn8",
  "issns": [
    "2666-0873"
  ],
  "landing_url": "https://doi.org/10.1016/j.jaccao.2026.07.008",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "heading",
      "Part 1: Cardio-Oncology & Immunology Special Issue"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7172530977",
  "pdf_url": null,
  "pmcid": "PMC13699032",
  "pmid": "42554546",
  "published": "2026-08-05",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/5jgkw1za8xcn8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:43Z",
      "native_id": "PMC13699032",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jaccao.2026.07.008"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Inflammatory Cell Profiles in Early- and Late-Manifestation Immune Checkpoint Inhibitor Myocarditis",
  "title_text": "Inflammatory Cell Profiles in Early- and Late-Manifestation Immune Checkpoint Inhibitor Myocarditis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:35:39Z",
  "url": "https://research.draconitic.com/paper/5jgkw1za8xcn8",
  "venue": "JACC: CardioOncology",
  "versions": []
}