title: Left ventricular hypertrophy with strain and aortic stenosis.
abstract: BACKGROUND
  ECG left ventricular hypertrophy with strain is associated with an adverse prognosis in aortic stenosis. We investigated the mechanisms and outcomes associated with ECG strain.
  
  
  RESULTS
  One hundred and two patients (age, 70 years [range, 63-75 years]; male, 66%; aortic valve area, 0.9 cm(2) [range, 0.7-1.2 cm(2)]) underwent ECG, echocardiography, and cardiovascular magnetic resonance. They made up the mechanism cohort. Myocardial fibrosis was determined with late gadolinium enhancement (replacement fibrosis) and T1 mapping (diffuse fibrosis). The relationship between ECG strain and cardiovascular magnetic resonance was then assessed in an external validation cohort (n=64). The outcome cohort was made up of 140 patients from the Scottish Aortic Stenosis and Lipid Lowering Trial Impact on Regression (SALTIRE) study and was followed up for 10.6 years (1254 patient-years). Compared with those without left ventricular hypertrophy (n=51) and left ventricular hypertrophy without ECG strain (n=30), patients with ECG strain (n=21) had more severe aortic stenosis, increased left ventricular mass index, more myocardial injury (high-sensitivity plasma cardiac troponin I concentration, 4.3 ng/L [interquartile range, 2.5-7.3 ng/L] versus 7.3 ng/L [interquartile range, 3.2-20.8 ng/L] versus 18.6 ng/L [interquartile range, 9.0-45.2 ng/L], respectively; P<0.001) and increased diffuse fibrosis (extracellular volume fraction, 27.4±2.2% versus 27.2±2.9% versus 30.9±1.9%, respectively; P<0.001). All patients with ECG strain had midwall late gadolinium enhancement (positive and negative predictive values of 100% and 86%, respectively). Indeed, late gadolinium enhancement was independently associated with ECG strain (odds ratio, 1.73; 95% confidence interval, 1.08-2.77; P=0.02), a finding confirmed in the validation cohort. In the outcome cohort, ECG strain was an independent predictor of aortic valve replacement or cardiovascular death (hazard ratio, 2.67; 95% confidence interval, 1.35-5.27; P<0.01).
  
  
  CONCLUSIONS
  ECG strain is a specific marker of midwall myocardial fibrosis and predicts adverse clinical outcomes in aortic stenosis.
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Anoop S V
authors.initials: AS
authors.lastname: Shah
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.). cchin03m@gmail.com.
authors.forename: Calvin W L
authors.initials: CW
authors.lastname: Chin
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Vassilis
authors.initials: V
authors.lastname: Vassiliou
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: S Joanna
authors.initials: SJ
authors.lastname: Cowell
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Mhairi
authors.initials: M
authors.lastname: Doris
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: T'ng Choong
authors.initials: TC
authors.lastname: Kwok
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Scott
authors.initials: S
authors.lastname: Semple
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Vipin
authors.initials: V
authors.lastname: Zamvar
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Audrey C
authors.initials: AC
authors.lastname: White
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Graham
authors.initials: G
authors.lastname: McKillop
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Boon
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Prasad
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: From the British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK (A.S.V.S., C.W.L.C., M.D., T.C.K., S.S., A.C.W., N.A.B., N.L.M., D.E.N., M.R.D.); Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore (C.W.L.C.); Royal Brompton Hospital, London, UK (V.V., S.K.P.); National Heart and Lung Institute, Imperial College, London, UK (V.V., S.K.P.); NHS Lothian, Edinburgh, UK (S.J.C., A.C.W., G.M., N.A.B., N.L.M., D.E.N., M.R.D.); Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK (S.S., D.E.N.); and Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK (V.Z.).
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis / Q000401:mortality / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume; D019210:Troponin I / Q000097:blood
chemical_list: D019210:Troponin I
keywords: aortic valve stenosis; fibrosis; hypertrophy, left ventricular; troponin I