Author + information
- Received June 21, 2016
- Revision received October 4, 2016
- Accepted October 5, 2016
- Published online November 6, 2017.
- Calvin W.L. Chin, MDa,b,
- Russell J. Everett, MDa,
- Jacek Kwiecinski, MDa,c,
- Alex T. Vesey, MD, PhDa,
- Emily Yeunga,
- Gavin Essona,
- William Jenkins, MDa,
- Maria Kooa,
- Saeed Mirsadraee, MDa,
- Audrey C. Whitea,
- Alan G. Japp, MD, PhDa,
- Sanjay K. Prasad, MDd,
- Scott Semple, PhDe,
- David E. Newby, MD, PhDa and
- Marc R. Dweck, MD, PhDa,∗ ()
- aBHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
- bDepartment of Cardiovascular Science, National Heart Center, Singapore
- cFirst Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
- dRoyal Brompton Hospital, London, United Kingdom
- eClinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom
- ↵∗Address for correspondence:
Dr. Marc R. Dweck, BHF/Centre for Cardiovascular Science, Chancellor’s Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom.
Objectives Cardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality.
Background Progressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis.
Methods In a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up.
Results iECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m2 vs. 16.1 ± 3.2 ml/m2 in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m2; 51% of patients), extracellular expansion (iECV ≥22.5 ml/m2; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups. Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009).
Conclusions CMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis. This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement. (The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936)
Dr. Chin was supported by the National Research Foundation, Ministry of Health, Singapore. Drs. Newby, Dweck, and Everett were supported by the British Heart Foundation (CH/09/002, FS/14/78/31020, and CH/09/002/26360, respectively). Dr. Dweck was also supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). Dr. Newby was also supported by a Wellcome Trust Senior Investigator Award (WT103782AIA).
Dr. Semple has been a consultant for GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Chin and Everett contributed equally to this work.
- Received June 21, 2016.
- Revision received October 4, 2016.
- Accepted October 5, 2016.
- 2017 American College of Cardiology Foundation