Temporal relationship of conduction system disease and ventricular dysfunction in LMNA cardiomyopathy

Abstract

Background: LMNA 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 results: We 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.

Conclusions: ECG 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.

Figure 1. Conduction system disease and arrhythmia

The following clinical categories are shown according to their age of detection. The age of detection of any ECG abnormality (solid line); the age of detection of any diagnosis of arrhythmia (dotted line); the age of detection of conduction system disease (dashed line); the age of detection of His bundle disease (dashed and dotted line).

Figure 2. Ventricular dysfunction

The numbers of cases with ventricular dysfunction are shown on the vertical axis and the age detected is shown on the horizontal axis for the following categories: DCM, (solid line); left ventricular enlargement, censored at the time of development of DCM (dotted line); left ventricular systolic dysfunction with no left ventricular enlargement, censored at the time of development of DCM (dashed line).

Figure 3. Age of detection of ECG abnormalities in subjects who subsequently developed left ventricular dysfunction

The median age of first detection of any ECG abnormality was 41 years (solid line) and the median age of first detection of any left ventricular dysfunction (left ventricular enlargement, systolic dysfunction without LVE, or DCM) was 48 years (dotted line) is shown. By log rank test the curves were different from one another (p=0.016).