Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients with Aortic Valve Stenosis

Objectives: The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS). Background: Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS. Methods: A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis. Results: There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th–75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th–75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05). Conclusions: Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload

Sex differences in heart failure

Heart failure (HF) represents a global pandemic health problem with a high impact on health-care costs, affecting about 26 million adults worldwide. The overall HF prevalence and incidence are ~2% and ~0.2% per year, respectively, in Western countries, with half of the HF population with reduced ejection fraction (HFpEF) and half with preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Sex differences may exist in HF. More males have HFrEF or HFmrEF and an ischemic etiology, whereas more females have HFpEF and hypertension, diastolic dysfunction, and valvular pathologies as HF etiologies. Females are generally older, have a higher EF, higher frequency of HF-related symptoms, and lower NYHA functional status. Generally, it is observed that female HF patients tend to have more comorbidities such as atrial fibrillation, diabetes, hypertension, anemia, iron deficiency, renal disease, arthritis, frailty, depression, and thyroid abnormalities. However, overall, females have better prognosis in terms of mortality and hospitalization risk compared with men, regardless of EF. Potential sex differences in HF characteristics may be underestimated because of the underrepresentation of females in cardiovascular research and, in particular, the sex imbalance in clinical trial enrollment may avoid to identify sex-specific differences in treatments’ benefit