Author + information
- Received April 21, 2017
- Revision received July 16, 2017
- Accepted August 15, 2017
- Published online July 2, 2018.
- Thomas A. Treibel, PhDa,b,
- Rebecca Kozor, PhDa,c,
- Marianna Fontana, PhDb,
- Camilla Torlasco, MDa,
- Patricia Reant, MD, PhDd,
- Sveeta Badiani, MBBSa,
- Maria Espinoza, MDa,
- John Yap, MDa,
- Javier Diez, PhDe,f,
- Alun D. Hughes, PhDb,
- Guy Lloyd, MDa,b and
- James C. Moon, MDa,b,∗ ()
- aBarts Heart Centre, St Bartholomew’s Hospital, London, United Kingdom
- bInstitute of Cardiovascular Science, University College London, London, United Kingdom
- cSydney Medical School, University of Sydney, Sydney, Australia
- dUniversity Hospital Center of Bordeaux, and University of Bordeaux, Bordeaux, France
- eProgram of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
- fCIBERCV, Carlos III Institute of Health, Madrid, Spain
- ↵∗Address for correspondence:
Prof. James C. Moon, Barts Heart Centre, St Bartholomew’s Hospital, 2nd Floor, King George V Block, London EC1A 7BE, United Kingdom.
Objectives The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers.
Background AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping.
Methods This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy.
Results In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001).
Conclusions CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471)
This research was undertaken at University College London Hospital, which received a proportion of funding from the UK Department of Health National Institute for Health Research Biomedical Research Centers funding scheme. Dr. Treibel was supported by Doctoral Research Fellowships from the National Institute for Health Research, United Kingdom (NIHR-DRF-2013-06-102). Dr. Fontana was supported by a Clinical Research Training Fellowship from the British Heart Foundation (grants FS/12/56/29723). Dr. Moon has received grant funding from GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 21, 2017.
- Revision received July 16, 2017.
- Accepted August 15, 2017.
- 2018 The Authors