High-Sensitivity Troponin I and NT-proBNP as Early Indicators of Disease Severity and Prognostic Markers in Immune Checkpoint Inhibitor-Associated Fulminant Myocarditis

Background: The study aims to investigate the utility of high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) measured at initial presentation as indicators of disease severity and prognostic markers in patients with immune checkpoint inhibitor (ICI)-associated myocarditis. While these biomarkers reflect myocardial injury and ventricular dysfunction—consequences of the underlying pathology—their levels at diagnosis may aid in early risk stratification and identification of patients likely to follow a fulminant course. Methods: This study implemented a retrospective cohort design, involving 341 patients identified with myocarditis associated with immune checkpoint inhibitors (ICIs). The participants were divided into two categories: those with fulminant myocarditis (62 subjects) and those with non-fulminant myocarditis (279 subjects). An in-depth examination was conducted on their clinical features, biomarker concentrations, and health outcomes. To ascertain the predictive capability of these biomarkers, multivariable logistic regression analyses and survival assessments were utilized. Additionally, a subgroup analysis was carried out by classifying patients into high and low biomarker groups according to the optimal cutoff points determined through receiver operating characteristic (ROC) curve evaluations. The subgroups were then compared regarding treatment modalities (including immunosuppressive therapy and mechanical circulatory support) and clinical outcomes (including ICU admission, complications, and survival). Results: Patients with fulminant myocarditis had significantly higher hs-cTnI (1.38 ± 0.56 vs. 0.22 ± 0.10ng/mL) and NT-proBNP (2384.43 ± 912.67 vs. 528.72 ± 192.33pg/mL) levels (both P < 0.001). Both biomarkers were independent predictors of fulminant disease, with areas under the ROC curve of 0.984 and 0.981, respectively. Optimal cutoffs were 0.435 ng/mL for hs-cTnI and 970.07 pg/mL for NT-proBNP. Patients above these thresholds received more intensive therapy and had worse outcomes, including lower 3-month survival (75.86% vs. 97.64%, P < 0.001). Conclusion: Hs-cTnI and NT-proBNP levels at presentation are strong indicators of myocardial injury severity and ventricular dysfunction in ICI-associated myocarditis. Their measurement facilitates early risk stratification, identifying patients at highest risk for fulminant disease who may benefit from intensive monitoring and timely intervention. Additionally, pre-existing cardiovascular comorbidities remain crucial for identifying vulnerable populations prior to ICI initiation. Keywords: tumor treatment-related fulminant myocarditis, high-sensitivity cardiac troponin I, N-terminal pro-brain natriuretic peptide, immune checkpoint inhibitors, risk stratification, prognostic biomarkers