Abstract 14269: Characteristics and Long-term Prognosis of Patients With Dilated Cardiomyopathy and Ventricular Tachycardia due to Lamin A/C Gene Mutations
Background: Lamin A/C (LMNA) gene mutations are associated with familial dilated cardiomyopathy (DCM) complicated by atrioventricular (AV) conduction disturbances, progressive severe heart failure, malignant ventricular arrhythmias (MVAs) and sudden cardiac death (SCD). Although SCD appears to be caused by ventricular tachyarrhythmias, clinical characteristics and long-term prognosis of patients with LMNA mutations remain to be elucidated.
Methods and Results: We experienced 6 familial DCM patients with LMNA mutations in 3 pedigrees (6 males, 43.7±4.5 [SD] years). All patients had several ventricular tachycardia (VT) events, and 3 suffered from incessant VT refractory to multiple anti-arrhythmic drugs (AAD) and were assigned to RFCA. Their ECGs showed similar QRS morphologies, characterized by inferior axis and negative QRS polarity in both leads aVR and aVL, suggesting that the VT originated from the basal ventricular septum. Electrophysiological studies showed that the VTs had multiple exits around the basal anterior ventricular septum in all 3 RFCA cases. Multiple procedures including epicardial ablation reduced VT events and made it possible to control incessant VTs, but did not completely eliminate VTs, resulting in VT recurrence in all patients. In one autopsy case with 3 RFCA procedures, myocardial fibrofatty changes suspected to be the arrhythmogenic substrate were observed at deep site in the basal ventricular septum beyond the reach of both endo- and epicardial RF lesions. Despite a combined modality therapies with RFCA and cardiac devices (implantable cardioverter-defibrillator in 1 and cardiac resynchronization therapy in 5), all patients were repeatedly hospitalized due to VT events or worsening heart failure, and 4 died (sepsis or multiple organ failure related to worsening heart failure in 3, and lung disease in 1). Thus, most VTs associated with LMNA cardiomyopathy originated from the basal ventricular septum and were resistant to RFCA probably because of the deep intramural focus.
Conclusion: These results demonstrate that patients with DCM due to LMNA are characterized by VTs refractory to all available optimized therapies, resulting in progressive severe heart failure and death.
- © 2013 by American Heart Association, Inc.