title: Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I.
abstract: BACKGROUND
  Limb girdle muscular dystrophies (LGMD) are inclusive of 7 autosomal dominant and 14 autosomal recessive disorders featuring progressive muscle weakness and atrophy. Studies of cardiac function have not yet been well-defined in deficiencies of dysferlin (LGMD2B) and fukutin related protein (LGMD2I). In this study of patients with these two forms of limb girdle muscular dystrophy, cardiovascular magnetic resonance (CMR) was used to more specifically define markers of cardiomyopathy including systolic dysfunction, myocardial fibrosis, and diastolic dysfunction.
  
  
  METHODS
  Consecutive patients with genetically-proven LGMD types 2I (n = 7) and 2B (n = 9) and 8 control subjects were enrolled. All subjects underwent cardiac magnetic resonance (CMR) on a standard 1.5 Tesla clinical scanner with cine imaging for left ventricular (LV) volume and ejection fraction (EF) measurement, vector velocity analysis of cine data to calculate myocardial strain, and late post-gadolinium enhancement imaging (LGE) to assess for myocardial fibrosis.
  
  
  RESULTS
  Sixteen LGMD patients (7 LGMD2I, 9 LGMD2B), and 8 control subjects completed CMR. All but one patient had normal LV size and systolic function; one (type 2I) had severe dilated cardiomyopathy. Of 15 LGMD patients with normal systolic function, LGE imaging revealed focal myocardial fibrosis in 7 (47%). Peak systolic circumferential strain rates were similar in patients vs. controls: εendo was -23.8 ± 8.5vs. -23.9 ± 4.2%, εepi was -11.5 ± 1.7% vs. -10.1 ± 4.2% (p = NS for all). Five of 7 LGE-positive patients had grade I diastolic dysfunction [2I (n = 2), 2B (n = 3)]. that was not present in any LGE-negative patients or controls.
  
  
  CONCLUSIONS
  LGMD2I and LGMD2B generally result in mild structural and functional cardiac abnormalities, though severe dilated cardiomyopathy may occur. Long-term studies are warranted to evaluate the prognostic significance of subclinical fibrosis detected by CMR in these patients.
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio 43205, USA.
authors.forename: Xiomara Q
authors.initials: XQ
authors.lastname: Rosales
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Moser
authors.forename: Tam
authors.initials: T
authors.lastname: Tran
authors.forename: Beth
authors.initials: B
authors.lastname: McCarthy
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dunn
authors.forename: Philip
authors.initials: P
authors.lastname: Habib
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002648:Child; D003287:Contrast Media; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005260:Female; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications* / Q000235:genetics; D009154:Mutation; D009206:Myocardium / Q000473:pathology*; D009820:Ohio; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D013318:Stroke Volume; D016277:Ventricular Function, Left; D055815:Young Adult
chemical_list: D003287:Contrast Media; C114839:DYSF protein, human; D000073939:Dysferlin; C113587:FKTN protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins