Evidence map›Paper›PMID 42207985›Full record

Observational studyESC heart failure2026

Novel insights into the histopathological characteristics of immune checkpoint inhibitor-related myocarditis.

Tatsuya Nishikawa, Tomoyuki Otani, Hironori Yamamoto, Taku Yasui, Motohiro Shingu, Yuto Osumi, Kenta Ishibashi, Yoshihiko Ikeda, Akiko Nonaka, Yuko Fukuda and 24 more

Abstract readMulticenter StudyObservational Study
In one paragraph

Observational study in ESC heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors.

Tatsuya NishikawaDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.ORCID 0000-0002-3754-8593
Tomoyuki OtaniDepartment of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.ORCID 0000-0002-4351-324X
Hironori YamamotoDepartment of Onco-Cardiology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka City, Osaka 541-8567, Japan.
Taku YasuiDepartment of Onco-Cardiology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka City, Osaka 541-8567, Japan.
Motohiro ShinguDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.ORCID 0009-0008-4147-5893
Yuto OsumiDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.
Kenta IshibashiDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.
Yoshihiko IkedaDepartment of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.
Akiko NonakaDepartment of Oncocardiology, Hyogo Cancer Center, Akashi, Japan.
Yuko FukudaDepartment of Oncocardiology, Hyogo Cancer Center, Akashi, Japan.
Ryosuke MuraiDepartment of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Yutaka FurukawaDepartment of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Shigeo HaraDepartment of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.
Daigo SawakiDepartment of Cardiology, Jichi Medical University Hospital, Tochigi, Japan.ORCID 0000-0003-1417-2033
Noritoshi HiranumaDepartment of Cardiology, Ako City Hospital, Ako, Japan.
Yoshitaka OhashiDepartment of Cardiology, Ako City Hospital, Ako, Japan.ORCID 0000-0002-4790-3229
Tomofumi TakayaDivision of Cardiovascular Medicine, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Japan.ORCID 0000-0001-5775-8072
Yujiro AsadaDepartment of Diagnostic Pathology, Miyazaki Medical Association Hospital, Miyazaki, Japan.ORCID 0000-0001-5105-2159
Natsuko IshiiDepartment of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan.
Toru KuboDepartment of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan.ORCID 0000-0001-5681-8854
Yoshiharu KinugasaDepartment of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University, Yonago, Japan.
Emi DateDepartment of Diagnostic Pathology, Kishiwada City Hospital, Kishiwada, Japan.
Norishige IizukaDepartment of Diagnostic Pathology, Kishiwada City Hospital, Kishiwada, Japan.
Naka SakamotoDivision of Cardiology and Nephrology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Takeshi KitaiDepartment of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Suita, Japan.
Chisato IzumiDepartment of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Suita, Japan.ORCID 0000-0002-3282-1327
Kisaki AmemiyaDepartment of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.
Keiko Ohta-OgoDepartment of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.ORCID 0000-0001-9822-3461
Kensaku NishihiraDepartment of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan.ORCID 0000-0002-1718-3830
Mitsuo KinugasaDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.
Toshio ShimokawaDepartment of Biostatistics, School of Medicine, Wakayama Medical University, Wakayama, Japan.
Koichi TamitaDepartment of Cardiovascular Medicine, Akashi Medical Center, Akashi, Japan.
Masashi FujitaDepartment of Onco-Cardiology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka City, Osaka 541-8567, Japan.
Kinta HatakeyamaDepartment of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.ORCID 0000-0001-7729-1836

Funding

JSPS KAKENHI 24K10118
6 · The paper itself

Abstract

BACKGROUND AND

aimsPathological examination is commonly used to diagnose immune checkpoint inhibitor (ICI)-related myocarditis. However, well-organized clinicopathological evidence remains limited. In this study, we aimed to investigate the pathological and clinical characteristics of myocarditis to enhance understanding.

methodsThis multicentre retrospective observational study included 38 patients diagnosed with or suspected of having ICI-related myocarditis. Patients were stratified using the pathological grading system proposed by Palaskas et al. Lymphocyte infiltration was assessed using both global and hot-spot (hotspot) methods. Immunohistochemistry was performed for lymphocytes, macrophages, and inflammatory markers, including human leucocyte antigen-DR isotype (HLA-DR), programmed death-ligand 1 (PD-L1), granzyme B, and tenascin C.

resultsAn increased infiltration of CD3, CD4, CD8-positive T cells, and CD68 and CD163-positive macrophages was observed with higher pathological grades. HLA-DR and tenascin C (clone 4F10) were sensitive markers of inflammation, whereas PD-L1 and tenascin C (clone 4C8) were more specific for high-grade inflammation. Global assessment more accurately predicted myocarditis-related mortality than hotspot assessment, although both methods similarly predicted fulminant myocarditis and major adverse cardiac events. Two patients presented with suspected ICI-mediated non-inflammatory left ventricular dysfunction (NILVD), with minimal myocardial inflammation.

conclusionsPathological grading using both global and hotspot assessment is valuable for the diagnosis and risk stratification of ICI-related myocarditis. As low-grade inflammation is not uncommon, supplementary markers such as HLA-DR, granzyme B, tenascin C, and PD-L1 may aid diagnosis. Furthermore, ICI-mediated NILVD may encompass cases of low-grade myocarditis.

Indexed as

Immune Checkpoint InhibitorsMyocarditisMyocardiumAdultBiomarkersFemaleHumansImmunohistochemistryMacrophagesMaleMiddle AgedRetrospective StudiesBiomarkersImmune Checkpoint InhibitorsHLA-DR antigensImmune checkpoint inhibitorsInflammationLigandsMyocarditis

Identifiers

PMID42207985
PMCPMC13298878

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.