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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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
Volume12
Issue number1
Early online date13 Dec 2017
DOIs
Publication statusPublished - Jan 2019

Fingerprint

Ventricular Remodeling
Aortic Valve Stenosis
Sex Characteristics
Matrix Metalloproteinase 3
Syndecan-4
Brain Natriuretic Peptide
Fibrosis
Biomarkers
Syndecan-1
Pressure
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 2
Gadolinium
Aortic Valve
Echocardiography
Referral and Consultation
Magnetic Resonance Imaging
Confidence Intervals

Keywords

  • Journal Article
  • aortic stenosis
  • biomarkers
  • remodeling
  • sex
  • FIBROSIS
  • VALVE STENOSIS
  • CARDIOVASCULAR MAGNETIC-RESONANCE
  • HEART-FAILURE
  • MYOCARDIAL-PERFUSION RESERVE
  • MATRIX METALLOPROTEINASES
  • DEPENDENT DIFFERENCES
  • EXTRACELLULAR VOLUME
  • DYSFUNCTION
  • GENDER-DIFFERENCES

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Symptom Onset in Aortic Stenosis : Relation to Sex Differences in Left Ventricular Remodeling. / Singh, Anvesha (Corresponding Author); Chan, Daniel C. S.; Greenwood, John P.; Dawson, Dana K; Sonecki, Piotr; Hogrefe, Kai; Kelly, Damian J.; Dhakshinamurthy, Vijay; Lang, Chim C.; Khoo, Jeffery P; Sprigings, David; Steeds, Richard P; Zhang, Ruiqi; Ford, Ian; Jerosch-Herold, Michael; Yang, Jing; Li, Zhuyin; Ng, Leong L; McCann, Gerry P.

In: JACC. Cardiovascular Imaging, Vol. 12, No. 1, 01.2019, p. 96-105.

Research output: Contribution to journalArticle

Singh, A, Chan, DCS, Greenwood, JP, Dawson, DK, Sonecki, P, Hogrefe, K, Kelly, DJ, Dhakshinamurthy, V, Lang, CC, Khoo, JP, Sprigings, D, Steeds, RP, Zhang, R, Ford, I, Jerosch-Herold, M, Yang, J, Li, Z, Ng, LL & McCann, GP 2019, 'Symptom Onset in Aortic Stenosis: Relation to Sex Differences in Left Ventricular Remodeling', JACC. Cardiovascular Imaging, vol. 12, no. 1, pp. 96-105. https://doi.org/10.1016/j.jcmg.2017.09.019
Singh, Anvesha ; Chan, Daniel C. S. ; Greenwood, John P. ; Dawson, Dana K ; Sonecki, Piotr ; Hogrefe, Kai ; Kelly, Damian J. ; Dhakshinamurthy, Vijay ; Lang, Chim C. ; Khoo, Jeffery P ; Sprigings, David ; Steeds, Richard P ; Zhang, Ruiqi ; Ford, Ian ; Jerosch-Herold, Michael ; Yang, Jing ; Li, Zhuyin ; Ng, Leong L ; McCann, Gerry P. / Symptom Onset in Aortic Stenosis : Relation to Sex Differences in Left Ventricular Remodeling. In: JACC. Cardiovascular Imaging. 2019 ; Vol. 12, No. 1. pp. 96-105.
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abstract = "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.",
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TY - JOUR

T1 - Symptom Onset in Aortic Stenosis

T2 - Relation to Sex Differences in Left Ventricular Remodeling

AU - Singh, Anvesha

AU - Chan, Daniel C. S.

AU - Greenwood, John P.

AU - Dawson, Dana K

AU - Sonecki, Piotr

AU - Hogrefe, Kai

AU - Kelly, Damian J.

AU - Dhakshinamurthy, Vijay

AU - Lang, Chim C.

AU - Khoo, Jeffery P

AU - Sprigings, David

AU - Steeds, Richard P

AU - Zhang, Ruiqi

AU - Ford, Ian

AU - Jerosch-Herold, Michael

AU - Yang, Jing

AU - Li, Zhuyin

AU - Ng, Leong L

AU - McCann, Gerry P

N1 - Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - aortic stenosis

KW - biomarkers

KW - remodeling

KW - sex

KW - FIBROSIS

KW - VALVE STENOSIS

KW - CARDIOVASCULAR MAGNETIC-RESONANCE

KW - HEART-FAILURE

KW - MYOCARDIAL-PERFUSION RESERVE

KW - MATRIX METALLOPROTEINASES

KW - DEPENDENT DIFFERENCES

KW - EXTRACELLULAR VOLUME

KW - DYSFUNCTION

KW - GENDER-DIFFERENCES

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UR - http://www.mendeley.com/research/symptom-onset-aortic-stenosis-relation-sex-differences-left-ventricular-remodeling

U2 - 10.1016/j.jcmg.2017.09.019

DO - 10.1016/j.jcmg.2017.09.019

M3 - Article

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JO - JACC. Cardiovascular Imaging

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