Aims: We sought to identify patterns of myocardial fibrosis in vivo in patients with lamin cardiomyopathy, and to determine its functional significance.
Methods and 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.