Epicardial ablation in genetic cardiomyopathies: a new frontier

Brugada syndrome (BrS) and several cardiomyopathies, including dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction (LVNC), and hypertrophic cardiomyopathy (HCM), share common genetic mutations and are associated with an arrhythmogenic substrate (AS) and increased risk of sudden cardiac death (SCD) due to malignant ventricular arrhythmias. We report a family in which a SCN5A mutation was found in both a father and daughter who presented with different phenotypes: the father with LVNC and the daughter with BrS, suggesting SCN5A may be important in cases of overlap between BrS and these various other cardiomyopathies and arrhythmias. Additionally, we report a family in which a MYBPC3 mutation was found in a father, daughter, and son, but they also presented with different phenotypes: the father with HCM and the daughter and son with BrS, suggesting patients with cardiomyopathies or BrS exhibiting sarcomeric mutations may have common genetic pathways that ultimately diverge into different phenotypes. Generally, prevention of SCD may involve the use of an implantable cardioverter-defibrillator and/or pharmaceutical therapy. However, patients continue to experience difficulties with this treatment. Epicardial mapping together with ajmaline challenge used to identify the AS in BrS patients can be used to identify and ablate the AS in cardiomyopathy patients, thus preventing the recurrence of ventricular tachycardia/fibrillation and reducing or eliminating the need for shock or pharmacological therapy. Future studies and longer follow-up times are warranted to understand the fullest duration of the therapeutic potential of this ajmaline and map-guided ablation therapy.