Optimizing troponin T screening for immune checkpoint inhibitor-associated myocarditis

Background Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as ICI-associated myocarditis (ICI-myocarditis). Current ESC guideline endorses cycle-dependent monitoring with high-sensitivity troponin-T (hs-TnT), yet treatment intervals vary from two to six weeks. Purpose This study evaluates real-world hs-TnT dynamics for early identification of ICI-myocarditis. Methods We evaluated hs-TnT in two independent cohorts: a ‘fixed sampling cohort’ (FSC) of high-risk patients on combination ICI, measured at baseline and week six, and a ‘serial sampling cohort’ (SSC) on mono/ combination ICI, measured at each treatment cycle. Associations between baseline hs-TnT and ICI-myocarditis were assessed using logistic regression, and longitudinal changes with generalized estimating equations. Results In the FSC (6 cases and 141 non-cases), baseline hs-TnT did not differ significantly between groups (7.8 versus 6.0 ng/L, p=0.422), though 21% of non-cases exceeded the 14 ng/L threshold. In the SSC (8 cases and 156 non-cases), baseline hs-TnT was higher in cases (15 vs 10 ng/L, p=0.022), and 35% of all patients exceeded the 14 ng/L threshold. Median onset of ICI-myocarditis was in the FSC 25 days and in the SCC 40 days. In the SSC, non-linear models confirmed an early divergence in hs-TnT trajectories between groups (5% increase/cycle, p=0.004), while extended follow-up showed greater variability without additional diagnostic value. Conclusion Baseline hs-TnT mainly serves as reference, while repeated measurements at week-based intervals may improve early detection of ICI-myocarditis compared to cycle-based monitoring. These findings may implicate a shift from ESC guideline endorsed cycle-dependent monitoring, that may otherwise miss cases in regimens with extended ICI-dosing intervals.