Temporal Relationship of Conduction System Disease and Ventricular Dysfunction in LMNA Cardiomyopathy

BackgroundLMNA cardiomyopathy presents with electrocardiogram (ECG) abnormalities, conduction system disease (CSD), and/or arrhythmias before the onset of dilated cardiomyopathy (DCM). Knowing the time interval between the onset of CSD and its progression to DCM would help to guide clinical care.Methods and ResultsWe evaluated family members from 16 pedigrees previously identified to carry LMNA mutations for the ages of onset of ECG abnormalities, CSD, or arrhythmia and of left ventricular enlargement (LVE) and/or systolic dysfunction. Of 103 subjects, 64 carried their family LMNA mutation, and 51 (79%) had ECG abnormalities with a mean age of onset of 41.2 years (range 18–76). Ventricular dysfunction was observed in 26 with a mean age of onset of 47.6 years (range 28–82); at diagnosis 9 had systolic dysfunction but no LVE, 5 had LVE but no systolic dysfunction, and 11 had DCM. Of 16 subjects identified with ECG abnormalities who later developed ventricular dysfunction, the median ages of onset by log-rank analyses were 41 and 48 years, respectively.ConclusionsECG abnormalities preceded DCM with a median difference of 7 years. Clinical surveillance should occur at least annually in those at risk for LMNA cardiomyopathy with any ECG findings.