Abstract
BACKGROUND: Immune-checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI-related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI-treated patients are limited. METHODS: All patients treated with ICI who had hs-TnT (high-sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs-TnT elevation were assessed. Risks of cardiac events were compared across hs-TnT elevation causes. RESULTS: Of 5423 patients treated with ICI, 1669 had post-ICI hs-TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1-year follow-up. Hs-TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7-238.0], P<0.001), followed by hs-TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs-TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4-15.3], P<0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. CONCLUSIONS: Hs-TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs-TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.