Association of peak cardiac troponin with prognosis of immune checkpoint inhibitor associated myocarditis
M Ono, R Murai, T Nishikawa, T Otani, M Fujita, K Hatakeyama, Y FurukawaAbstract
Background
Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare and often fatal immune-related complication. Although an elevated cardiac troponin (cTn) level is an essential component in the diagnosis of ICI-associated myocarditis, significance of the peak cTn value as a prognostic marker remains to be elucidated.Purpose: The purpose of this study is to clarify the association between peak cTn value and clinical outcomes in patients with ICI-associated myocarditis.
Methods
We retrospectively enrolled 38 patients diagnosed with or suspected of having ICI-related myocarditis via biopsy or autopsy from 9 institutes in Japan between September 2018 and December 2024 Rates of increase in peak cTn values were expressed as a fold-change relative to the upper reference limit (URL) at each institution. The adverse outcome measure was myocarditis-related death, and the favorable outcome measure was complete recovery from myocarditis. The myocarditis-related death was defined as death during hospitalization for myocarditis. The complete recovery was defined by complete resolution of acute symptoms, normalization of biomarkers, and recovery of LVEF after discontinuation of immunosuppression. After excluding one patient without cTn measurement, 37 patients were finally analyzed.
Results
Among the 37 patients, myocarditis-related death occurred in 5 (13%) patients. Those patients showed higher peak cTn levels than patients without cardiac death. (median 5432 vs 136 pg/ml, p=0.008; 207-fold vs 8.3-fold of URL, p=0.009). No significant differences were observed in age, sex, comorbidities, or ICI treatment efficacy. 21 (55%) patients completely recovered from myocarditis. 15 of the patients with complete recovery and 11 of those without complete recovery received steroid treatment, respectively. There were also no significant differences in age, sex, comorbidities, peak cTn values. ROC analysis demonstrated discriminatory ability of cTn fold increase for risk of cardiac death (AUC 0.87, 95% CI 0.74–1.00). A cutoff of cTn ≥22-fold above the URL achieved 100% sensitivity and 100% negative predictive value. In Firth-corrected logistic regression analysis adjusted for steroid therapy, cTn elevation ≥22-fold remained to be an independent predictor of cardiac death (Odds ratio [OR] 16.6, 95% confidence interval [CI] 2.78-3862, p=0.01). A mild cTn elevation (≥1.3-fold above the URL) was highly sensitive for identifying patients who failed to achieve complete recovery. In Firth-corrected logistic regression analysis adjusting for steroid therapy, a cTn elevation ≥1.3-fold was independently associated with a significantly lower likelihood of complete recovery (OR 0.06, 95% CI 0.01-0.55, p = 0.011).
Conclusion
In patients with ICI-associated myocarditis, the magnitude of peak cTn elevation predicts myocarditis-related mortality. Even a low level-elevation of cTn levels may be associated with a risk of remaining cardiac dysfunction after myocarditis.