Symptom Onset in Aortic Stenosis - Relation to Sex Differences in Left Ventricular Remodelling

Anvesha Singh (Lead / Corresponding author), Daniel C. S. Chan, John P. Greenwood, Dana K. Dawson, Piotr Sonecki, Kai Hogrefe, Damian J. Kelly, Vijay Dhakshinamurthy, Chim 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: To establish sex differences in remodelling and outcome in aortic stenosis (AS) and their associations with biomarkers of myocardial fibrosis.

Background: The remodelling response and timing of symptoms is highly variable in AS, and gender plays an important role.

Methods: 174 patients (133 male, mean age 66.2 ± 13.3 years) with asymptomatic moderate to severe AS underwent comprehensive stress cardiac magnetic resonance (CMR) imaging, trans-thoracic echocardiography (TTE) and biomarker analysis (MMP-2, 3, 7, 8 and 9, TIMP-1, 4, syndecan-1 and 4 and NT-proBNP), and were followed up at 6 monthly intervals. A primary endpoint was a composite of typical AS symptoms necessitating referral for AVR, cardiovascular death or major adverse cardiovascular events.

Results: For a similar severity of AS, male patients demonstrated higher indexed LV volumes and mass, more concentric remodelling (higher LV mass/volume), a trend to more late gadolinium enhancement (LGE) (present in 51.1% male vs. 34.1% female, p=0.057) and higher extra-cellular volume index than female patients (13.27 [11.5, 17.0] vs. 11.53 [10.5, 13.5] ml/m2, p=0.017), with worse systolic and diastolic function and higher MMP-3 and syndecan-4 levels, whilst females had higher septal E/e’. Male sex was independently associated with indexed LV mass (β=13.32 (9.59-17.05), p<0.001). During median follow-up of 374 (IQR 351-498) days, a primary outcome, driven by spontaneous symptom onset, occurred in 21.8% of male and 43.9% of female patients (RR 0.50 (CI 0.31, 0.80), p=0.004). Measures of AS severity were associated with the primary outcome in both sexes, whereas NT-proBNP, MMP3 and mass/volume were only associated in males.
Conclusions: In AS, females tolerate pressure overload with less concentric remodelling and myocardial fibrosis but are more likely to develop symptoms. This may be related to higher wall stress and filling pressures in females.
Original languageEnglish
Pages (from-to)96-105
Number of pages10
JournalJACC. Cardiovascular Imaging
Issue number1
Early online date13 Dec 2017
Publication statusPublished - Jan 2019


  • aortic stenosis
  • sex
  • remodelling
  • biomarkers


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