title: Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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/m2vs. 16.1 ± 3.2 ml/m2in 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).
  
  
  
  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).
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Department of Cardiovascular Science, National Heart Center, Singapore.
authors.forename: Calvin W L
authors.initials: CWL
authors.lastname: Chin
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Everett
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kwiecinski
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Vesey
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Emily
authors.initials: E
authors.lastname: Yeung
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Esson
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Jenkins
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Koo
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mirsadraee
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Audrey C
authors.initials: AC
authors.lastname: White
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Japp
authors.affiliation: Royal Brompton Hospital, London, United Kingdom.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Prasad
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Scott
authors.initials: S
authors.lastname: Semple
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: BHF/Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: marc.dweck@ed.ac.uk.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D001706:Biopsy; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D016022:Case-Control Studies; D018450:Disease Progression; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
keywords: T1 mapping; aortic stenosis; fibrosis; hypertrophy; magnetic resonance imaging; myocardium