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Sex Differences in Immune Checkpoint Inhibitor-related Cardiotoxicity: A Propensity Score-matched Cohort Study
Abdul Rasheed Bahar1, Yasemin Bahar1, Paawanjot Kaur1
1Wayne State University, Department of Medicine, Detroit, MI.
Critical Pathways in Cardiology
|July 17, 2026
Summary
Biological sex influences cardiovascular risks from immune checkpoint inhibitors (ICIs). Males face higher risks of myocarditis and arrhythmias, while females have increased Takotsubo cardiomyopathy, highlighting sex-specific cardiotoxicity patterns.
Area of Science:
- Cardiology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial cancer therapies.
- Cardiovascular immune-related adverse events (irAEs) from ICIs cause significant morbidity and mortality.
- The role of biological sex in ICI-associated cardiotoxicity is not well-defined in real-world data.
Purpose of the Study:
- To investigate sex-based disparities in cardiovascular irAEs following ICI treatment.
- To compare the incidence of specific cardiovascular events between biological sexes after ICI initiation.
Main Methods:
- Retrospective cohort study utilizing the TriNetX global research network.
- Propensity score-matched analysis of adults initiating ICI therapy, stratified by biological sex.
- Primary outcome: incident myocarditis at 6 months, 1 year, and 2 years; secondary outcomes: arrhythmias, conduction abnormalities, cardiomyopathies.
Main Results:
- Females exhibited a lower risk of myocarditis at all time points (6 months, 1 year, 2 years).
- Males had higher risks of myocarditis, atrial fibrillation, ventricular arrhythmias, high-degree atrioventricular block, ischemic cardiomyopathy, and dilated cardiomyopathy.
- Females showed a higher incidence of Takotsubo cardiomyopathy compared to males.
Conclusions:
- Significant sex-related differences exist in ICI-associated cardiotoxicity.
- Males are at higher risk for myocarditis and certain arrhythmias, whereas females are more prone to Takotsubo cardiomyopathy.
- Further research is needed to elucidate the clinical implications of these sex-specific cardiovascular risk patterns.