title: Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I.
abstract: OBJECTIVE
  The mechanisms of cardiac dysfunction in limb girdle muscular dystrophy 2I (LGMD2I) are unclear. This study assessed deficits in cardiac morphology, function, and metabolism quantitatively in patients with a confirmed genetic diagnosis of the homozygous c.826C > A FKRP (fukutin-related protein) mutation, using a comprehensive magnetic resonance (MR) examination.
  
  
  RESULTS
  Ten patients (7 male and 3 female) and 10 matched control subjects were recruited prospectively. Cardiac morphology by cine imaging, cardiac torsion and strain by MR tagging, and cardiac energetics by phosphorus-31 MR spectroscopy were measured. LGMD2I subjects were found to have a significant reduction in peak cardiac torsion (3.9 ± 1.3° vs. 6.4 ± 1.5°, P = 0.04), and in the ratio of torsion to endocardial strain (0.31 ± 0.05 vs. 0.51 ± 0.14, P = 0.03), compared with control subjects. The impairment in torsion correlated strongly with reduction in EF (r = 0.93, P < 0.001). Peak circumferential and longitudinal strains were preserved in the patients, however [LGMD2I, 16.4 ± 3.2% vs. 18.3 ± 3.5%, non-significant (NS); and LGMD2I, 17.0 ± 3.0% vs. 18.4 ± 3.5%, NS]. Cardiac cine analysis demonstrated reduced EF (47 ± 7% vs, 58 ± 4%, P = 0.02) and stroke volume (61 ± 11 mL vs. 81 ± 13 mL, P = 0.04), though no evidence of LV hypertrophy was found. The ratio of phosphocreatine to ATP (PCr/ATP) was reduced in the LGMD2I subjects compared with controls (1.50 ± 0.24 vs. 1.94 ± 0.12, P = 0.0001).
  
  
  CONCLUSIONS
  The loss of torsion with preservation of circumferential and longitudinal strain in LGMD2I is a unique finding and suggests subepicardial dysfunction with abnormal transmission of force across the cardiac wall.
authors.affiliation: Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. k.g.hollingsworth@ncl.ac.uk
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Willis
authors.forename: Matthew G D
authors.initials: MG
authors.lastname: Bates
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Dixon
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: John
authors.initials: J
authors.lastname: Bourke
authors.forename: Guy A
authors.initials: GA
authors.lastname: MacGowan
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications* / Q000235:genetics; D009154:Mutation; D010430:Pentosyltransferases; D010496:Pericardium / Q000503:physiopathology*; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics; D013057:Spectrum Analysis; D013318:Stroke Volume; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases
keywords: Cardiac tagging; Limb girdle muscular dystrophy; MRI; Muscular dystrophy; Spectroscopy