Mid-myocardial fibrosis by cardiac magnetic resonance in patients with lamin A/C cardiomyopathy: possible substrate for diastolic dysfunction.
OBJECTIVE
We sought to identify patterns of myocardial fibrosis in vivo in patients with lamin cardiomyopathy, and to determine its functional significance.


RESULTS
Eleven patients sharing the identical mutation in LMNA without contraindication to magnetic resonance were identified from a 1016-member pedigree. Eight autopsy hearts from deceased relatives were reviewed. Patients and age-matched controls underwent cardiac magnetic resonance that included measures of cardiac function and late gadolinium enhancement (LGE). LGE-CMR identified midmyocardial fibrosis of the basal interventricular septum in 5 of 11 LMNA patients that was identical to that seen in 6 autopsy specimens of related genotype-positive family members; this was not present in any of 11 controls. LGE-CMR was positive in the 5 oldest patients in the cohort, age 46 +/- 6 years compared to 24 +/- 10 years for LGE-negative subjects (p = 0.003). Systolic function was abnormal in 2 subjects, both with myocardial fibrosis. LGE-positivity distinguished patients with diastolic dysfunction by mitral inflow velocities from those with normal diastolic function; these patients also had significant left atrial enlargement compared to controls (p < 0.05).


CONCLUSIONS
LGE-CMR can identify myocardial fibrosis under genetic control in vivo in patients with heritable cardiomyopathy similar in distribution to that observed at autopsy. Mid-myocardial fibrosis may form the substrate for diastolic dysfunction in these patients.
Raman
Subha V
SV
Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210-1252, USA. Raman.1@osu.edu
Sparks
Elizabeth A
EA
Baker
Peter M
PM
McCarthy
Beth
B
Wooley
Charles F
CF
D000328:Adult; D001344:Autopsy; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D003971:Diastole / Q000502:physiology; D005260:Female; D005355:Fibrosis; D005838:Genotype; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008137:Longitudinal Studies; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D018709:Statistics, Nonparametric
D034904:Lamin Type A