Author + information
- Received October 3, 2019
- Revision received October 31, 2019
- Accepted November 4, 2019
- Published online January 20, 2020.
- Russell J. Everett, MD, PhDa,∗ (, )@russeverett3,
- Thomas A. Treibel, MD, PhDb,
- Miho Fukui, MDc,
- Heesun Lee, MDd,
- Marzia Rigolli, MD, DPhile,
- Anvesha Singh, MD, PhDf,
- Petra Bijsterveld, MAg,
- Lionel Tastet, MSch,
- Tarique Al Musa, MDg,
- Laura Dobson, MDg,
- Calvin Chin, MD, PhDi,
- Gabriella Captur, MD, PhDj,
- Sang Yong Om, MDk,
- Stephanie Wiesemann, MDl,
- Vanessa M. Ferreira, MD, DPhile,
- Stefan K. Piechnik, PhDe,
- Jeanette Schulz-Menger, MDl,
- Erik B. Schelbert, MDc,
- Marie-Annick Clavel, DVM, PhDh,
- David E. Newby, MD, PhDa,
- Saul G. Myerson, MDe,
- Phillipe Pibarot, DVM, PhDh,
- Sahmin Lee, MDk,
- João L. Cavalcante, MDc,
- Seung-Pyo Lee, MD, PhDd,
- Gerry P. McCann, MDf,
- John P. Greenwood, MD, PhDg,
- James C. Moon, MDb and
- Marc R. Dweck, MD, PhDa
- aCentre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom
- bBarts Health NHS Trust and University College London, London, United Kingdom
- cUPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, Pennsylvania
- dDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- eUniversity of Oxford Centre for Clinical Magnetic Resonance Research, BHF Centre of Research Excellence (Oxford), NIHR Biomedical Research Centre (Oxford), Oxford, United Kingdom
- fDepartment of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
- gMultidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
- hInstitut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Université Laval, Québec City, Québec, Canada
- iNational Heart Center Singapore, Singapore
- jInherited Heart Muscle Disease Clinic, Department of Cardiology, Royal Free Hospital, NHS Foundation Trust, London, United Kingdom
- kDivision of Cardiology, Asan Medical Center Heart Institute, University of Ulsan College of Medicine, Seoul, Republic of Korea
- lCharité Campus Buch ECRC, Berlin, and Helios Clinics Cardiology Germany, DZHK partner site, Berlin, Germany
- ↵∗Address for correspondence:
Dr. Russell Everett, Room SU:305, Centre for Cardiovascular Sciences, Chancellor’s Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom.
Background Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.
Objectives This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.
Methods Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.
Results Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).
Conclusions In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.
This study was supported by grants from the Korean Health Technology R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (HI16C0225 and HI15C0399) and the National Institute for Health Research (NIHR) infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Drs. Singh and McCann have received support from the NIHR Leicester Biomedical Research Centre and the NIHR Leicester Clinical Research Facility related to this work. Dr. McCann has received support from the National Institute for Health Research (NIHR CDF 2014-07-045). Mr. Tastet is supported by a doctoral scholarship from Fonds de Recherche en Santé-Québec. Dr. Clavel holds a New National Investigator Award from the Heart and Stroke of Canada and an Early Carrier Investigator Award from the Canadian Institute of Health Research. Dr. Newby is supported by the British Heart Foundation (CH/09/002, RG/16/10/32375, RE/18/5/34216) and a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Myerson is supported by the NIHR Oxford Biomedical Research Centre. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases from the Canadian Institutes of Health Research (CIHR); has received research grants (FDN 143225 and MOP-114997) from the CIHR; and has contracts with Edwards Lifesciences for echo corelab analyses and with Medtronic for in vitro studies with no personal compensation. Dr. Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). Dr. Schulz-Menger has served on an advisory board for Bayer. Dr. Schelbert has served on advisory boards for Bayer and Merck; and has received contrast donated by Bracco Diagnostics. Dr. Clavel has a core laboratory contract with Edwards Lifesciences; and has received a research grant from Medtronic. Dr. Cavalcante has received research grants from Edwards Lifesciences and Medtronic; has been a consultant for Boston Scientific, Siemens Healthineers, and Medtronic; and has received research support from Circle Cardiovascular Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 3, 2019.
- Revision received October 31, 2019.
- Accepted November 4, 2019.
- 2020 The Authors