Details of elevated troponin levels and clinical outcomes following immune checkpoint inhibitor treatment

Introduction Myocarditis is a life-threatening adverse event associated with immune checkpoint inhibitor (ICI) therapy, for which troponin is used as a biomarker for monitoring. Sometimes elevated troponin levels have been observed following ICI treatment; however, the detailed outcomes of patients with elevated troponin levels remain unclear. Purpose The purpose of this study was to determine the relationship between troponin elevation and clinical outcomes after ICI treatment. Methods This retrospective study included 267 patients whose troponin T levels were measured after the initiation of ICI treatment at our hospital in Japan, between October 2021 and July 2023. Results Elevations in troponin levels above the upper limit of normal (0.014 ng/mL) were observed in 114 patients (43%) following ICI treatment. Among these, 15 patients (13%) experienced cardiac adverse events; 13 were diagnosed with ICI-associated myocarditis according to Bonaca's criteria, and 2 were diagnosed with heart failure, all of whom exhibited troponin T levels exceeding 0.1 ng/mL at onset. Among the 13 patients with myocarditis, one patient with the highest troponin level at onset died of fulminant myocarditis, while the other 12 patients showed improvement of symptoms and a decrease in troponin levels with treatment. All patients with elevated troponin T levels below 0.1 ng/mL did not meet the criteria for myocarditis or other cardiac events and continued on ICI therapy with careful management. Figure 1 shows the difference in troponin T values between the baseline and the peak after the start of ICI. Even in the group of patients with no overt cardiac events (Figure 1B), troponin levels were significantly higher after ICI administration compared to before (p<0.01) (Figure 1). Figures 2A and 2B illustrate the maximum troponin levels in patients who died within one month of troponin measurement, those who died between one and three months, and other patients. Figure 2A includes all patients, while Figure 2B excludes patients with overt cardiac events from the comparison depicted in Figure 2A. Patients who died within one month of the troponin measurement demonstrated significantly higher troponin levels than the other groups, even among patients without overt cardiac events. Conclusion Patients who developed cardiac events had troponin levels above 0.1 ng/mL and required treatment. In addition, troponin levels in patients who died shortly after measurement were higher than in other patients, even among those without overt cardiac events. Elevated troponin levels are a useful biomarker for myocarditis and may serve as a potential marker of poor prognosis in these patients.