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

journal contribution
posted on 12.04.2018, 09:21 by Anvesha Singh, Daniel C.S. Chan, J. P. Greenwood, D. K. Dawson, P. Sonecki, K. Hogrefe, D. J. Kelly, V. Dhakshinamurthy, C. C. Lang, Jeffery P. Khoo, D.. Sprigings, R. P. Steeds, R. Zhang, I. Ford, M. Jerosch-Herold, J. Yang, Z. Li, Leong L. Ng, Gerry P. McCann
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.

History

Citation

JACC: Cardiovascular Imaging, 2017, in press

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

AM (Accepted Manuscript)

Published in

JACC: Cardiovascular Imaging

Publisher

Elsevier

issn

1936-878X

Copyright date

2017

Available date

13/12/2018

Publisher version

https://www.sciencedirect.com/science/article/pii/S1936878X17309877?via=ihub#!

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above

Language

en

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