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Sex Differences in Myocardial Fibrosis in Patients With Aortic Stenosis
Study Questions:
Does sex affect myocardial fibrosis assessed using cardiac magnetic resonance (CMR) imaging among patients with aortic stenosis (AS)?
Methods:
A total of 249 patients (mean age 66 ± 13 years, 30% women) with at least mild AS were recruited from two prospective observational cohort studies, and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify left ventricular (LV) 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), although women had a better cardiovascular risk profile than men, with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all p ≤ 0.10). Measures of AS severity (peak velocity, mean gradient, effective orifice area index) were not different between men and women. As expected, LV mass index measured by CMR imaging was lower in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median 29.0% [25th-75th percentiles, 27.4%-30.6%] vs. 26.8% [25th-75th percentiles 25.1%-28.7%], p < 0.0001) and more LGE (median 4.5% [25th-75th percentiles, 2.3%-7.0%] vs. 2.8% [25th-75th percentiles, 0.6%-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. The authors concluded that these findings further emphasize the sex-related differences in LV remodeling response to pressure overload.
Perspective:
Myocardial fibrosis is an important marker of LV decompensation and adverse events among patients with AS. This study adds to existing data suggesting that men and women exhibit important differences in LV remodeling in response to the pressure overload of AS, and suggests that in men, the expansion of ECV is driven mainly by AS severity and the extent of LV hypertrophy; whereas in women, the LV response to AS is more heterogeneous and multifactorial. Future studies need to be performed to determine whether outcomes among patients with AS can be improved by using CMR assessment of LV fibrosis to optimize the timing of intervention for AS. However, these data could at least in part explain some observed differences in outcomes between men and women after aortic valve replacement.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Echocardiography/Ultrasound, Magnetic Resonance Imaging, Hypertension
Keywords: Aortic Valve Stenosis, Contrast Media, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Imaging, Dyspnea, Dyslipidemias, Echocardiography, Doppler, Fibrosis, Gadolinium, Hypertension, Hypertrophy, Left Ventricular, Heart Valve Diseases, Magnetic Resonance Imaging, Myocardium, Risk Factors, Secondary Prevention
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