Prolonged Right Ventricular Ejection Delay in Brugada Syndrome depends on the type of SCN5a mutation. A bridge between Tissue Velocity Imaging and Genetics

Background Brugada Syndrome (BS) patients with a previous history of syncope or sustained ventricular arrhythmia have longer right ventricular ejection delays (RVED’s) when compared to asymptomatic BS patients. A genotype-phenotype relationship has not been shown for this non-invasive echocardiographic parameter. Different types of SCN5A variants displaying variable amounts of INA reduction, might have an impact on conduction delay and therefore also on RVED measurement. Objectives We aimed to establish whether BS patients carrying a more severe SCN5A variant leading to premature protein truncation (T), demonstrated a longer RVED when compared to missense variants (M).
Methods 24 BS patients (mean age 44.0 ± 14.1 years, 50.0% males) with (likely) pathogenic SCN5A variants were enrolled in this cross-sectional study. They were divided into T-carriers (n = 13) and M-carriers (n = 11). Using Tissue Velocity Imaging (TVI), the ejection delay of the RV (RVED, in ms) was measured as the time from the QRS onset to the onset of the systolic ejection wave at the end of the isovolumetric contraction (IVC).
Results T-carriers demonstrated longer RVED’s com- pared tot M-carriers (139.3±15.1 vs 123.0±11.5 ms, P = 0.007).
Conclusion This is the first report, using non-invasive TVI, to demonstrate that BS patients carrying T-var- iants have longer RVED’s indicating a more severe pheno- type. Given that RVED represents conduction delay, we provide additional evidence to further support the depolarization hypothesis in BS.