title: Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation.
abstract: BACKGROUND
  The optimum timing of surgery in asymptomatic patients with chronic severe primary degenerative mitral regurgitation (MR) remains controversial, and further markers are needed to improve decision-making. There are limited data that wall stress is increased in MR and may result in ventricular fibrosis. We investigated the hypothesis that chronic volume overload in MR is a stimulus for myocardial fibrosis using T1-mapping cardiac MRI.
  
  
  RESULTS
  A cross-sectional study of 35 patients (age 60 ± 14 years) with asymptomatic moderate and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45 ± 0.25 cm)(2) with no class I indication for surgery were compared with age and sex controls. Subjects were studied with cardiopulmonary exercise testing, echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial deformation was reduced with MR when left ventricular ejection fraction (67% ± 10%) and N-terminal pro B Natriuretic peptide (126 [76-428] ng/L) were within the normal range. Myocardial extracellular volume was increased (0.32 ± 0.07 versus 0.25 ± 0.02, P<0.01) and was associated with increased left ventricular end-systolic volume index (r=0.62, P<0.01), left atrial volume index (r=0.41, P<0.05) but lower left ventricular ejection fraction (r=-0.60, P<0.01), longitudinal function (mitral annular plane systolic excursion, r=-0.46, P<0.01), and peak VO2 max (r=-0.51, P<0.05). In a multivariable regression model, left ventricular end-systolic volume index and left atrial volume index were independent predictors of extracellular volume (r(2)=0.42, P<0.01).
  
  
  CONCLUSIONS
  Patients with asymptomatic MR demonstrate a spectrum of myocardial fibrosis associated with reduced myocardial deformation and reduced exercise capacity. Future work is warranted to investigate whether left ventricle fibrosis affects clinical outcomes.
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.). n.c.edwards@bham.ac.uk.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: William E
authors.initials: WE
authors.lastname: Moody
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: Mengshi
authors.initials: M
authors.lastname: Yuan
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: Peter
authors.initials: P
authors.lastname: Weale
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: Desley
authors.initials: D
authors.lastname: Neal
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.affiliation: From the Department of Cardiovascular Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom (N.C.E., W.E.M., J.N.T., R.P.S.); Departments of Cardiology (N.C.E., W.E.M., M.Y., J.N.T.) and Pathology (D.N.), University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and Imaging and Therapy Systems Department, Siemens Healthcare, Surrey, United Kingdom (P.W.).
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler; D017548:Echocardiography, Transesophageal; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D005355:Fibrosis; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: magnetic resonance imaging; mitral valve regurgitation; myocardial fibrosis