title: Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction.
  
  
  METHODS
  We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient.
  
  
  RESULTS
  Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging. In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE.
  
  
  CONCLUSIONS
  Impairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established.
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK. p.swoboda@leeds.ac.uk.
authors.forename: Peter P
authors.identifier: http://orcid.org/0000-0001-7162-7079
authors.initials: PP
authors.lastname: Swoboda
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Adam K
authors.initials: AK
authors.lastname: McDiarmid
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Bara
authors.initials: B
authors.lastname: Erhayiem
authors.affiliation: Division of Epidemiology and Biostatistics, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Law
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Garg
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.|Department of Medical Physics and Engineering, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Broadbent
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Ripley
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Tarique A
authors.initials: TA
authors.lastname: Musa
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Dobson
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Foley
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Fent
authors.affiliation: Inherited Cardiovascular Conditions Service, Leeds General Infirmary, Leeds, LS1 3EX, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Page
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Greenwood
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC) & Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Sven
authors.initials: S
authors.lastname: Plein
mesh_terms: D000328:Adult; D001696:Biomechanical Phenomena; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005355:Fibrosis; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology*; D009942:Organometallic Compounds / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013314:Stress, Mechanical; D013318:Stroke Volume; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol
keywords: Extracellular volume; Feature tracking; Hypertrophic cardiomyopathy; Strain; T1 mapping; Tissue tagging