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Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I
Author(s) -
Hollingsworth Kieren G.,
Willis Tracey A.,
Bates Matthew G.D.,
Dixon Ben J.,
Lochmüller Hanns,
Bushby Kate,
Bourke John,
MacGowan Guy A.,
Straub Volker
Publication year - 2013
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hft057
Subject(s) - medicine , limb girdle muscular dystrophy , cardiology , phosphocreatine , muscular dystrophy , cardiomyopathy , stroke volume , cardiac magnetic resonance imaging , left ventricular hypertrophy , heart failure , ejection fraction , magnetic resonance imaging , blood pressure , radiology , phenotype , biochemistry , chemistry , gene , energy metabolism
Aim 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. Methods and 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.