Clinical disease presentation and ECG characteristics of mutation carriers.

Objective: Mutations in the gene encoding lamins A and C of the nuclear lamina are a frequent cause of cardiomyopathy accounting for 5-8% of familial dilated cardiomyopathy (DCM). Our aim was to study disease onset, presentation and progression among mutation carriers.

Methods: Clinical follow-up data from 27 mutation carriers and 78 patients with idiopathic DCM without an mutation were collected. In addition, ECG data were collected and analysed systematically from 20 healthy controls.

Results: Kaplan-Meier analysis revealed no difference in event-free survival (death, heart transplant, resuscitation and appropriate implantable cardioverter-defibrillator therapy included as events) between mutation carriers and DCM controls (p=0.5). mutation carriers presented with atrial fibrillation at a younger age than the DCM controls (47 vs 57 years, p=0.003). Male mutation carriers presented with clinical manifestations roughly a decade earlier than females. In close follow-up non-sustained ventricular tachycardia was detected in 78% of mutation carriers. ECG signs of septal remodelling were present in 81% of the mutation carriers, 21% of the DCM controls and none of the healthy controls giving a high sensitivity and specificity for the standard ECG in distinguishing mutation carriers from patients with DCM and healthy controls.

Conclusions: Male mutation carriers present clinical manifestations at a younger age than females. ECG septal remodelling appears to distinguish mutation carriers from healthy controls and patients with DCM without mutations.