Abstract 9463: Septal Myocardial Function is reduced in Carriers of Lamin A/C mutations and related to Atrioventricular Block, Ventricular Tachycardia and Septal Fibrosis
Background: Mutations in the Lamin A/C gene may cause dilated cardiomyopathy accompanied by atrioventricular (AV) block, atrial fibrillation and ventricular tachycardia (VT). VTs are frequent and commonly occur before development of dilated cardiomyopathy. Mechanisms of AV block and VT in these patients are not fully understood.
Methods: We included 41 Lamin A/C mutation carriers with LV (left ventricular) EF 55±13%. PR interval from resting ECG and occurrence of VT by Holter monitoring and ICDs were recorded. Global and LV septal myocardial function were assessed by echocardiographic speckle tracking strain analysis. Nine patients were eligible for magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) to assess presence and distribution of myocardial fibrosis.
Results: VT was documented in 21 patients (51%). Prolonged PR interval (p<0.001), presence of AV block (p<0.001) and reduced global longitudinal strain (p=0.01) were markers of VT, while LVEF was not (p=0.55). LV septal function was markedly reduced compared to function in the rest of the left ventricle (strain -16.7% vs. -18.7%, p=0.001). Prolonged PR interval correlated with reduced LV septal function (R=0.41, p=0.03). By LGE MRI, 4/5 patients (80%) with documented VT showed LV septal fibrosis while no fibrosis was detected in 4/4 (100%) patients without VT (p=0.05). Fibrosis by MRI was located exclusively in the LV septum. PR interval was longer in patients with LV septal fibrosis compared to those without (320±26 vs. 172±66ms, p=0.002).
Conclusion: In Lamin A/C mutation carriers, myocardial function was most decreased in the LV septum and correlated to prolonged PR interval. Prolonged PR interval was a marker of VT. Myocardial LV septal fibrosis was associated with prolonged PR interval and VT. Localized fibrosis in the LV septum may be the mechanism behind AV block, VT and reduced LV septal function in Lamin A/C mutation carriers.
- © 2012 by American Heart Association, Inc.