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. 2025 Oct;7(6):708-721.
doi: 10.1016/j.jaccao.2025.06.009. Epub 2025 Aug 14.

Cardiac Troponin Screening and Clinical Outcomes in Patients Receiving Immunotherapy

Evaline Cheng  1 , Maja Ivanovic  2 , Antonia Chan  3 , Sidra Xu  4 , Miguel Franquiz  1 , Carissa Lee  5 , Jonathan You  6 , Muhammad Fazal  1 , Yann Le Guen  7 , Ryan Batchelder  1 , Sunil A Reddy  8 , Tamiko Katsumoto  9 , Kavitha Ramchandran  8 , A Dimitrios Colevas  8 , Saad Kahn  8 , Alice Fan  8 , Heather Wakelee  8 , Paul Cheng  1 , Eldrin F Lewis  1 , Sean M Wu  10 , Ronald Witteles  1 , Joel Neal  8 , Sarah Waliany  11 , Han Zhu  12
Affiliations
Free article

Cardiac Troponin Screening and Clinical Outcomes in Patients Receiving Immunotherapy

Evaline Cheng et al. JACC CardioOncol. 2025 Oct.
Free article

Abstract

Background: Immune checkpoint inhibitors (ICIs) are associated with cardiotoxicities such as myocarditis. However, data on the implementation and outcomes of cardiac biomarker screening remain limited.

Objectives: The aim of this study was to examine the impact of cardiac troponin I (cTnI) surveillance integrated with symptom-based triaging in patients receiving immunotherapy.

Methods: A single-center retrospective cohort study was conducted among adults who underwent routine serial cTnI monitoring during immunotherapy between January 2019 and October 2021. For patients with elevated cTnI, clinical presentation, management, and outcomes were analyzed. Major adverse cardiac events included arrhythmia, myocarditis, heart failure, acute coronary syndrome, stroke, and pericardial effusion. Patients were followed for 24 months from their first ICI dose.

Results: Among 428 patients (mean age 67.1 ± 13.9 years, 60.3% men), 42 (9.8%) had elevated cTnI detected through monitoring. Compared with symptomatic patients, asymptomatic patients more often underwent outpatient evaluation (88.0% vs 17.6%; P < 0.001) and continued immunotherapy (68.0% vs 35.3%; P < 0.001), whereas symptomatic patients more often underwent myocarditis-specific diagnostics such as cardiac magnetic resonance imaging (58.8% vs 8.0%; P = 0.001) and received immunosuppression (47.1% vs 8.0%; P = 0.008). The cumulative incidence of major adverse cardiac events at 1.5 years following cTnI elevation was 19.0% (95% CI: 7.0%-31.1%) and was significantly higher in symptomatic vs asymptomatic patients (subdistribution HR: 18.9; 95% CI: 2.2-162.5; P = 0.008). Symptomatic patients had a significantly higher risk for all-cause mortality at 2-year follow-up (HR: 3.24; 95% CI: 1.06-9.94; P = 0.04). In total, 6 patients were diagnosed with myocarditis, with no cardiac-related deaths.

Conclusions: cTnI surveillance integrated with symptom-based triaging can facilitate early intervention and treatment of cardiotoxicities such as myocarditis.

Keywords: biomarkers; immune checkpoint inhibitor; immune-related adverse events; immunotherapy; myocarditis; screening; surveillance; troponin.

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Conflict of interest statement

Funding Support and Author Disclosures Dr E. Cheng is supported by National Heart, Lung, and Blood Institute award F32HL176198. Dr Zhu has received support from National Institutes of Health grants 1K08HL16140501, R01HL174432, and R03HL173146; the Sarnoff Scholar Award; and the Stanford CVI Seed grant. Dr P. Cheng is supported by American Heart Association grant 20CDA35310303 and National Heart, Lung, and Blood Institute K08-HL153798. Dr Wu is supported by the Joan and Sanford I Weill Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Katsumoto has received research funding though Sanofi; and is a consultant for Genentech/Roche and Sonoma Biotherapeutics. Dr Witteles is a consultant and/or advisory board member for Pfizer, Alnylam, AstraZeneca, Janssen, Alexion, BridgeBio, and Novo Nordisk; and has received clinical trial support from Janssen, Ionis, Alynlam, Pfizer, and BridgeBio. Dr Wakelee has received research funding through Bayer, Bristol Myers Squibb, Merck, Helsinn, SeaGen, Xcovery, Genentech/Roche, and AstraZeneca/Medimmune; has served on advisory boards for Mirati, IOBiotech, Bristol Myers Squibb, Merck, Genentech/Roche, and AstraZeneca; holds leadership roles with the International Association for the Study of Lung Cancer and Eastern Cooperative Oncology Group–ACR Imaging Network. Dr Fan has received funding through Cancer Imaging Grants, Cancer Early Detection Grants, and Cancer Cytokines Grants from the U.S. Department of Defense, the National Cancer Institute, the Cancer League, the International Alliance for Cancer Detection, the University of Texas MD Anderson, Stanford Cancer Institute, and Stanford Radiology; has conducted novel technology development sponsored research for MagArray and Earli and clinical trials for novel agents in kidney cancer and prostate cancer; has received funding from the University of Washington, Calithera, and Filtricine; holds a Stanford cancer patent on biomarkers for response to treatment, on which she is an inventor, licensed by her startup, Molecular Decisions, until mid-2023; is the 2023 Precision Oncology Summit session chair; is on the Google Baseline Study return of results advisory board, administered by the Duke Clinical Research Institute (participation completed 2022); and holds founders’ stock in and is a board member for Molecular Decisions, a cancer treatment response biomarker company. Dr Khan has consulted for Foundation Medicine, Kineta, EMD, Serono, Roche Pakistan, Eisai, and Coherus; holds U.S. patent 11,747,345 (Prediction and Treatment of Immunotherapeutic Toxicity); and is on the board for Kineta. Dr Neal has been a speaker and/or presenter for CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI PeerView CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, the Medical Educator Consortium, and HMP Education; has consulted for AstraZeneca, Genentech/Roche, Exelixis, Takeda Pharmaceuticals, Eli Lilly, Amgen, and Iovance Biotherapeutics; has received grants from or has contracts with Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GlaxoSmithKline, Janssen, and AbbVie. Dr Reddy is on the IDEAYA phase 3 randomized trial monitoring board; has helped with clinical trials for Bristol Myers Squibb and Trisalus Life Sciences. Dr Waliany has consulted for AstraZeneca. Dr Ramchandran has received an honorarium from the Binaytara Foundation. Dr Lewis has received grants from Merck; has consulted for Merck, Akebia, Dal-Cor, AstraZeneca, and Intellia; and holds leadership roles with the American Heart Association and the American College of Cardiology. Dr Zhu has received grants from the National Heart, Lung, and Blood Institute; and has consulted for Skribe Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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