Exploring sex differences in myocardial fibrosis in patients with structurally normal hearts

Myocardial fibrosis as evaluated by cardiovascular magnetic resonance (CMR) plays a central role in pathophysiology of cardiovascular diseases and exhibits sex-specific differences. The goal of our study was to assess sex-related differences in fibrosis in patients with structurally normal hearts. We retrospectively studied patients undergoing clinical CMR at 1.5T with preserved cardiac function and no structural abnormalities. Standardized CMR protocols included cine imaging, T1 mapping, and late gadolinium enhancement (LGE) imaging. LGE presence, extent, and pattern, and extracellular volume fraction (ECV) were evaluated according to sex. The primary outcomes were all cause mortality and new-onset heart failure. Of 525 patients studied (43.1 ± 14.2 years, 69.5% female), 258 (49.1%) exhibited nonischemic LGE. Nonischemic LGE was more common in males (61.3% vs. 43.8%, p < 0.001), and remained so in multivariable analysis after adjustment for clinical covariates (OR 2.2, CI 1.17-4.13, p = 0.015). Women had higher ECV values (26.5 ± 4.3% vs. 23.2 ± 3.7, p < 0.001), and these sex differences remained significant in multivariable analysis (β coefficient = 1.29, p = 0.02). During 5.8 years follow-up there was no association between primary outcomes and nonischemic LGE. There was a trend towards association between ECV increase and all-cause mortality. The optimal ECV cutoff for all-cause mortality was 31.3% for females and 27.5% for males. Among patients with structurally normal hearts with preserved systolic function referred for clinical CMR exams, nonischemic LGE is more frequently observed in males, whereas ECV values are higher in females. ECV increase may be associated with all-cause mortality, both in female and male cohorts.