Sex difference in clinically suspected immune checkpoint inhibitor-related myocarditis: a single-institute...

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.

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.

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.

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.