Symptom Onset in Aortic Stenosis: Relation to Sex Differences in Left Ventricular Remodeling

Anvesha Singh (Corresponding Author), Daniel C. S. Chan, John P. Greenwood, Dana K Dawson, Piotr Sonecki, Kai Hogrefe, Damian J. Kelly, Vijay Dhakshinamurthy, Chim C. Lang, Jeffery P Khoo, David Sprigings, Richard P Steeds, Ruiqi Zhang, Ian Ford, Michael Jerosch-Herold, Jing Yang, Zhuyin Li, Leong L Ng, Gerry P McCann

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OBJECTIVES: The aim of this study was to establish sex differences in remodeling and outcome in aortic stenosis (AS) and their associations with biomarkers of myocardial fibrosis.

BACKGROUND: The remodeling response and timing of symptoms is highly variable in AS, and sex plays an important role.

METHODS: A total of 174 patients (133 men, mean age 66.2 ± 13.3 years) with asymptomatic moderate to severe AS underwent comprehensive stress cardiac magnetic resonance imaging, transthoracic echocardiography, and biomarker analysis (matrix metalloproteinase [MMP]-2, -3, -7, -8, and -9; tissue inhibitor matrix metalloproteinases-1 and -4; syndecan-1 and -4; and N-terminal pro-B-type natriuretic peptide), and were followed up at 6-month intervals. A primary endpoint was a composite of typical AS symptoms necessitating referral for aortic valve replacement, cardiovascular death, or major adverse cardiovascular events.

RESULTS: For a similar severity of AS, male patients demonstrated higher indexed left ventricular (LV) volumes and mass, more concentric remodeling (higher LV mass/volume), a trend to more late gadolinium enhancement (present in 51.1% men vs. 34.1% women; p = 0.057), and higher extracellular volume index than female patients (13.27 [interquartile range (IQR): 11.5 to 17.0] vs. 11.53 [IQR: 10.5 to 13.5] ml/m2, p = 0.017), with worse systolic and diastolic function and higher MMP-3 and syndecan-4 levels, whereas female patients had higher septal E/e'. Male sex was independently associated with indexed LV mass (β = 13.32 [IQR: 9.59 to 17.05]; p < 0.001). During median follow-up of 374 (IQR: 351 to 498) days, a primary outcome, driven by spontaneous symptom onset, occurred in 21.8% of male and 43.9% of female patients (relative risk: 0.50 [95% confidence interval: 0.31 to 0.80]; p = 0.004). Measures of AS severity were associated with the primary outcome in both sexes, whereas N-terminal pro-B-type natriuretic peptide, MMP-3, and mass/volume were only associated in men.

CONCLUSIONS: In AS, women tolerate pressure overload with less concentric remodeling and myocardial fibrosis but are more likely to develop symptoms. This may be related to higher wall stress and filling pressures in women.

Original languageEnglish
Pages (from-to)96-105
Number of pages10
JournalJACC. Cardiovascular Imaging
Issue number1
Early online date13 Dec 2017
Publication statusPublished - Jan 2019

Bibliographical note

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


  • Journal Article
  • aortic stenosis
  • biomarkers
  • remodeling
  • sex


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