Symptom onset in aortic stenosis: relation to sex differences in left ventricular remodelling

Singh, A. et al. (2019) Symptom onset in aortic stenosis: relation to sex differences in left ventricular remodelling. JACC: Cardiovascular Imaging, 12(1), pp. 96-105. (doi: 10.1016/j.jcmg.2017.09.019) (PMID:29248646)

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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.

Item Type:Articles
Additional Information:This study was funded by the National Institute for Health Research (NIHR-PDF 2011-04-51 GPM). The views expressed are those of the authors and not of the NHS, NIHR or the Department of Health. AS was funded by the NIHR Leicester Cardiovascular Biomedical Research Unit. NIHR Comprehensive Local Research Networks and the Leeds and Leicester NIHR Clinical Research Facilities provided further support. D.C.S.C is funded by the British Heart Foundation(FS/15/10/31223). The Luminex® assays were funded and performed by Bristol-Myers-Squibb, Princeton, NJ, USA
Glasgow Author(s) Enlighten ID:Sonecki, Dr P and Ford, Professor Ian
Authors: Singh, A., Chan, D. C.S., Greenwood, J. P., Dawson, D. K., Sonecki, P., Hogrefe, K., Kelly, D. J., Dhakshinamurthy, V., Lang, C. C., Khoo, J. P., Sprigings, D., Steeds, R. P., Zhang, R., Ford, I., Jerosch-Herold, M., Yang, J., Li, Z., Ng, L. L., and McCann, G. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:JACC: Cardiovascular Imaging
ISSN (Online):1876-7591
Published Online:13 December 2017
Copyright Holders:Copyright © 2017 American College of Cardiology Foundation
First Published:First published in JACC: Cardiovascular Imaging 12(1): 96-105
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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