Cardiac troponin identifies immune checkpoint inhibitor associated myocarditis and stratifies cardiovascular risk a systematic review and meta analysis

Background

Immune checkpoint inhibitors are associated with myocarditis, a rare but potentially life-threatening immune-related adverse event. Cardiac troponin is widely used in clinical practice; however, its diagnostic performance for immune checkpoint inhibitor–associated myocarditis and its prognostic value for subsequent cardiovascular outcomes have not been systematically quantified.

Purpose

To address two complementary objectives: (1) to evaluate the diagnostic performance of troponin elevation for immune checkpoint inhibitor–associated myocarditis, and (2) to assess the prognostic association between troponin elevation and major adverse cardiovascular events and mortality in adults receiving immune checkpoint inhibitor therapy.

Methods

We conducted a PRISMA-compliant systematic review and meta-analysis of MEDLINE, Embase, CENTRAL, and Scopus from inception to October 2025. Diagnostic studies evaluated troponin elevation against established myocarditis reference standards. Prognostic studies assessed associations between troponin elevation and time-to-event outcomes, including major adverse cardiovascular events and mortality. Effect estimates were pooled using random-effects models.

Results

Twenty-four studies comprising 7,258 patients were included. Across diagnostic studies (n=4; 1,051 patients), troponin elevation above assay-specific thresholds was strongly associated with confirmed immune checkpoint inhibitor–associated myocarditis (pooled log odds ratio 4.14, 95% confidence interval 2.80–5.48; I²=0%).

In prognostic analyses, troponin elevation was associated with a significantly increased risk of major adverse cardiovascular events (pooled hazard ratio 6.14, 95% confidence interval 3.61–10.45) and with increased mortality (pooled hazard ratio 1.95, 95% confidence interval 1.36–2.81). Studies reporting higher or persistent troponin elevations demonstrated greater cardiovascular risk.

Conclusions

Troponin elevation in patients receiving immune checkpoint inhibitors identifies myocardial injury and provides clinically relevant risk stratification for adverse cardiovascular outcomes. While troponin demonstrates high sensitivity for immune checkpoint inhibitor–associated myocarditis and prognostic value for subsequent events, variability in assays and thresholds limits its specificity as a standalone diagnostic test, underscoring the need for integrated clinical assessment.Diagnostic Performance Forest Plot  MACE/CV Events Forest Plot