Sex-related differences in myocardial fibrosis among patients with aortic stenosis: A systematic review and meta-analysis.

Background: Aortic stenosis (AS) leads to pathological myocardial remodeling, particularly fibrosis, which contributes to adverse outcomes including heart failure, arrhythmias, and mortality. Evidence suggests sex-specific differences in fibrotic response, but individual studies are underpowered for definitive conclusions. This Methods: Three databases were searched for studies comparing male and female patients with AS reporting CMR-derived measures. The primary outcomes were late gadolinium enhancement (LGE%), infarct-related and non-infarct-related LGE, extracellular volume (ECV) and Septal E/e'. Effect sizes were expressed as risk ratios (RR) for binary outcomes and mean differences (MD) for continuous outcomes, each with 95% confidence intervals (CI), using random-effects models. Study quality was appraised with the Newcastle-Ottawa Scale, and certainty of evidence was graded using the GRADE framework. Results: Seven studies (n = 2,105; 1,246 males) were included. No significant difference was observed in LGE% (MD 0.13; 95 %CI -0.93 to 1.18; p = 0.770), and risks of infarct-related LGE between sexes (RR 1.61; 95 %CI 0.90 to 2.89; p = 0.080). Males had higher risk of non-infarct LGE (RR 1.51; 95 %CI 1.34 to 1.70; p = 0.002). There were no significant differences in ECV (MD -0.45; 95 %CI -2.34 to 1.44; p = 0.506) and Septal E/e' between sexes (MD -1.87; 95 %CI -4.05 to 0.32; p = 0.072). Conclusion: This