Sex Dimorphism in the Myocardial Response to Aortic Stenosis

Figures

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  Figure 1. Remodeling by Cardiac Magnetic Resonance and Echocardiography Patients were categorized into 4 patterns of left ventricular (LV) geometric adaption: normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. For cardiac magnetic resonance, categories were defined by using body surface area–indexed LV mass (LVMi), indexed LV end-diastolic volume (EDVi), and mass/volume ratio. For 2-dimensional echocardiography, categories were defined by using body surface area–LVMi, end-diastolic cavity dimension, and relative wall thickness.

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  Figure 2. Sex Differences in Left Ventricular Pattern of Remodeling in Aortic Stenosis (A) Cardiac magnetic resonance found marked sex differences in left ventricular remodeling (chi-square test = 34; p < 0.001). Normal geometry (82% female) and concentric remodeling (60% female) were predominantly seen in women, whereas concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) in men. (B) This outcome was not apparent by 2-dimensional (2D) echocardiography (female: normal geometry 56%, concentric remodeling 51%, concentric hypertrophy 38%, and eccentric hypertrophy 39% [chi-square test = 2.7; p = 0.40]). Percentages are expressed as male/female split per remodeling category.

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  Figure 3. Sex, Left Ventricular Hypertrophy, and Decompensation (A) Indexed left ventricular mass (LVMi) and left ventricular ejection fraction (LVEF) by sex. Men had greater LVMi (98 ± 23 g/m2 vs. 75 ± 20 g/m2; p < 0.001) and lower LVEF than women (67 ± 16% vs. 74 ± 13%; p < 0.001). (B) LVMi and LVEF by N-terminal pro–brain natriuretic peptide (NT-proBNP) ratio greater (gray dots) or less than 1 (blue dots), which were higher in men than women (0.33 [interquartile range: 0.09 to 1.12] vs. 0.11 [interquartile range: 0.05 to 0.35]; p = 0.04). BSA = body surface area.

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  Figure 4. LGE Pattern in Severe Aortic Stenosis (A) No late gadolinium enhancement (LGE). (B) Focal papillary muscle and right ventricular (RV) insertion point LGE. (C) Focal mid-wall LGE in the anterolateral wall. Diffuse, patchy myocardial LGE ranging from (D) mild to (E) moderate to (F) severe LGE burden, associated with papillary muscle RV insertion and RV free wall LGE. (G) Noninfarct, subendocardial, and papillary muscle LGE. (H) Dilated cardiomyopathy pattern LGE. (I) Full thickness infarct in the thinned inferior wall.

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  Figure 5. Left Ventricular Remodeling in Aortic Stenosis by Multimodality Imaging There are 4 images each for all 4 patterns of remodeling: continuous-wave Doppler assessment of aortic stenosis severity (top left); Steady State Free Precession short-axis cine clip demonstrating the pattern of remodeling (as described in Figure 1) (top right); phase-sensitive inversion recovery late gadolinium enhancement image for focal fibrosis (bottom left); extracellular volume fraction map for diffuse fibrosis (bottom right).

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  Figure 6. Sex Dimorphism in Myocardial Response to AS Aortic stenosis (AS) is a disease of both valve and LV. Sex differences may play a role in disease phenotyping. The present study investigated 168 patients with severe symptomatic AS by using echocardiography (echo), cardiac magnetic resonance (CMR), and biomarkers. There were no sex differences in AS severity or functional capacity, but CMR captured a sex dimorphism in the LV remodeling pattern, missed by 2-dimensional echocardiography and more adverse in men with more LV dysfunction (by LVEF, N-terminal pro–brain natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hsTnT]) and myocardial fibrosis (focal and diffuse). Given equal valve severity, LV associations with AS appear more maladaptive in men, with more extreme sex differences than previously reported. AVAi = indexed aortic valve area; Vmax = peak velocity; other abbreviations as in Figures 1 and 3.