Serial cardiac troponin measurements for predicting immune checkpoint inhibitor-associated cardiotoxicity in adults with cancer: a systematic review and meta-analysis

Abstract Background/Introduction Immune checkpoint inhibitors improve outcomes across several cancers but may lead to immune-mediated cardiotoxicity, including myocarditis. Although cardiac troponin monitoring is recommended especially for baseline assessment, its prognostic value when measured serially during immune checkpoint inhibitor therapy is not well defined. Purpose To evaluate whether serial troponin elevation during immune checkpoint inhibitor therapy is associated with myocarditis, major adverse cardiovascular events and mortality in adults with cancer. Methods A prospectively registered systematic review and meta-analysis was conducted using established methodological standards. PubMed, Embase and a major trials registry were searched to August 2025. Eligible studies included adults on immune checkpoint inhibitor therapy with baseline and at least one follow-up troponin measurement and reported outcomes by troponin status. Patients with any troponin elevation during follow up (≥ assay upper reference limit or study-specific abnormal threshold) were compared with those without elevation. Random-effects models generated risk ratios (RR) with 95% confidence intervals (CI). When comparative estimates were not estimable, single-arm random-effects models summarised prevalence among patients with troponin elevation. Results Thirteen cohort studies (n = 2,604) were included; 563 patients (21.6%) developed troponin elevation during follow-up (mean 14 months). Troponin elevation was associated with higher risk of myocarditis (RR 57.9; 95% CI 28.1–119.5; I² = 0%). For composite major adverse cardiovascular events, effect estimates were directionally similar but imprecise, with substantial heterogeneity (RR 22.5; 95% CI 0.5–1078.4; I² = 86%). All-cause mortality was higher among patients with elevated troponin (RR 1.8; 95% CI 1.2–2.8). In single-arm analyses, the pooled prevalence of any-cause immune checkpoint inhibitor interruption was 31.2% (95% CI 13.0–52.4%) and 15.8% (95% CI 4.4–31.6%) for cardiovascular-related interruption. Sensitivity analyses were generally consistent, although event definitions and absolute rates varied. Conclusion(s) Troponin elevation during immune checkpoint inhibitor therapy is consistently associated with myocarditis and may help identify patients at increased risk of other cardiovascular complications and mortality. Given the observational design and heterogeneity across studies, these findings should be interpreted cautiously, but they support the need for prospective evaluation of standardised troponin-based surveillance strategies in cardio-oncology, particularly early in treatment.