Clinical significance of early asymptomatic high-sensitivity troponin T elevation in patients receiving immune checkpoint inhibitors
M Akagi, M Yamamoto, N Nakanishi, T Nakashima, K TsujitaAbstract
Background
Routine troponin monitoring is recommended during immune checkpoint inhibitor (ICI) therapy; however, interpretation of troponin elevations often causes uncertainty among oncologists and cardiologists, and the clinical significance of asymptomatic elevation remains unclear.
Purpose
To describe high-sensitivity troponin T (hs-TnT) trajectories during ICI therapy and to evaluate the clinical impact of early asymptomatic hs-TnT elevation.
Methods
We retrospectively identified consecutive patients treated with ICIs at a single center between 2022 and 2023. Eligible patients had a baseline hs-TnT measurement and at least one follow-up hs-TnT measurement within 3 months of ICI initiation. The Elevated group was defined as any follow-up hs-TnT value meeting both criteria: ≥0.014 ng/mL and ≥1.8 times the baseline level. Patients who experienced a cardiovascular (CV) event before the follow-up sampling date were excluded. Patients were followed for up to 1 year after the follow-up sampling date. The primary endpoint was CV events within 1 year (including immune-related myocarditis) occurring after sampling. Secondary endpoints were all-cause mortality, immune-related adverse events (irAEs) excluding myocarditis, and early CV events within 6 months after sampling. Time-to-event outcomes were assessed using Kaplan–Meier analyses with log-rank tests and Cox proportional hazards models adjusted for age and sex.
Results
Among 530 ICI-treated patients, 357 were included (median age 69 years; 66.9% male). In 271 patients with complete serial measurements, hs-TnT levels at 1 and 3 months were significantly higher than baseline, indicating an upward trajectory (Wilcoxon signed-rank tests with multiplicity adjustment). Overall, 51 patients (14.3%) were classified as Elevated and 306 (85.7%) as Non-elevated. Within 1 year, CV events occurred in 13.7% vs 7.5%, and all-cause mortality in 52.9% vs 37.9% of the Elevated and Non-elevated groups, respectively. Kaplan–Meier analyses showed no significant difference in 1-year CV events between groups, whereas the Elevated group had a higher incidence of early CV events within 6 months. All-cause mortality was consistently higher in the Elevated group. In age- and sex-adjusted Cox models, hs-TnT elevation was not associated with 1-year CV events (HR 2.08; 95% CI 0.89–4.85; p=0.08), but was associated with early CV events within 6 months (HR 3.28; 95% CI 1.32–8.15; p=0.01) and higher all-cause mortality (HR 1.60; 95% CI 1.05–2.44; p=0.03). No association was observed with irAEs excluding myocarditis.
Conclusions
Early asymptomatic hs-TnT elevation within 3 months of ICI initiation was associated with increased all-cause mortality and a higher risk of early CV events, but not with 1-year CV events. Serial hs-TnT monitoring during ICI therapy may aid risk stratification in this population. Figure 2