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Background: About 50% of normal‐flow/low‐gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and Vpeak measurements. Methods and Results: Doppler‐echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/Vpeak compared with normal stage (both P≤0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (−42%) compared with severe (−35%) AS (P˂0.0001). Comprehensive Doppler‐echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/Vpeak and aortic valve calcification divided by the cross‐sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients with normal‐flow/low‐gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal‐AC group (16% and 12% compared with 2%; P=0.03). Conclusions: Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severity

Background: About 50% of normal‐flow/low‐gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and Vpeak measurements. Methods and Results: Doppler‐echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/Vpeak compared with normal stage (both P≤0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (−42%) compared with severe (−35%) AS (P˂0.0001). Comprehensive Doppler‐echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/Vpeak and aortic valve calcification divided by the cross‐sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients with normal‐flow/low‐gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal‐AC group (16% and 12% compared with 2%; P=0.03). Conclusions: Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severity

Rationale: Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification (AVC) loads than men for the same AS hemodynamic severity. Objective: We thus aimed to assess sex-differences in aortic valve fibro-calcific remodelling. Methods and Results: One hundred and twenty-five patients underwent Doppler-echocardiography and multidetector-computed-tomography within 3 months prior to aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed and fibrosis degree was determined. Sixty-four men and 39 women were frequency-matched for age, body mass index (BMI), hypertension, renal disease, diabetes, and AS severity. Mean age was 75±9years, mean gradient (41±18mmHg) and indexed aortic valve area (0.41±0.12cm2/m2) were similar between men and women (all p=0.18). Median AVC (1973[1124-3490]AU) and mean valve weight (2.36±0.99g) were lower in women compared to men (both p<0.0001). AVC density correlated better with valve weight in men (r2=0.57; p<0.0001) than in women (r2=0.26; p=0.0008). After adjustment for age, BMI, AVC density and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (p=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (p=0.01) and Masson's trichrome staining revealed a greater proportion of dense connective tissue (p=0.02) in women compared to men. Conclusions: In this series with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared to men. These findings suggest that the pathophysiology of the disease and thus potential targets for drug development may be different according to sex.

Rationale: Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification (AVC) loads than men for the same AS hemodynamic severity. Objective: We thus aimed to assess sex-differences in aortic valve fibro-calcific remodelling. Methods and Results: One hundred and twenty-five patients underwent Doppler-echocardiography and multidetector-computed-tomography within 3 months prior to aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed and fibrosis degree was determined. Sixty-four men and 39 women were frequency-matched for age, body mass index (BMI), hypertension, renal disease, diabetes, and AS severity. Mean age was 75±9years, mean gradient (41±18mmHg) and indexed aortic valve area (0.41±0.12cm2/m2) were similar between men and women (all p=0.18). Median AVC (1973[1124-3490]AU) and mean valve weight (2.36±0.99g) were lower in women compared to men (both p<0.0001). AVC density correlated better with valve weight in men (r2=0.57; p<0.0001) than in women (r2=0.26; p=0.0008). After adjustment for age, BMI, AVC density and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (p=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (p=0.01) and Masson's trichrome staining revealed a greater proportion of dense connective tissue (p=0.02) in women compared to men. Conclusions: In this series with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared to men. These findings suggest that the pathophysiology of the disease and thus potential targets for drug development may be different according to sex.