Sex difference in clinically suspected immune checkpoint inhibitor-related myocarditis: a single-institute retrospective study with seven-year follow-up.

[BACKGROUND] Immune checkpoint inhibitors (ICIs) can enhance antitumor immunity but they also cause severe myocarditis. The impact of sex on presentation, biomarkers, and outcomes remains unclear. This study investigates sex-specific risk factors and predictors in clinically suspected ICI-induced myocarditis.

[METHOD] Patients diagnosed with clinically suspected ICI-induced myocarditis at a single institute (2018-2024) were retrospectively reviewed. Baseline characteristics, laboratory markers, echocardiographic parameters, and outcomes, were compared between female and male. The primary endpoint was all-cause mortality. The composite endpoint included all-cause mortality, myocardial infarction, malignant arrhythmias, clinically suspected myocarditis recurrence, cardiogenic shock, severe infection, tumor progression, and assisted ventilation. Sex-stratified analyses were performed to identify predictors of adverse outcomes using Cox regression, with additional sensitivity analyses including propensity score matching (PSM) and bootstrap validation.

[RESULTS] The cohort comprised 135 males (74%) and 44 females (26%), with a median follow-up of 36.1 months (interquartile range: 12.4-61.3 months). Female had better overall survival (p = 0.0071), though 30-day mortality and cardiac mortality were similar between sexes. Male also had a higher hazard of adverse outcomes than female with composite endpoint (p = 0.006). In multivariable models, male sex remained independently associated with higher all-cause and composite mortality (HR = 2.56, p = 0.001). Myoglobin and pro-BNP were significant predictors among males, whereas no consistent biomarker predictors were identified in females. The findings remained robust after PSM and bootstrap resampling.

[CONCLUSION] Significant sex-specific differences exist in clinically suspected ICI-induced myocarditis. Female sex is associated with better survival, underscoring the need for sex-based risk stratification.