Prolonged Right Ventricular Ejection Delay in Brugada Syndrome Depends on the Type of SCN5A Variant - Electromechanical Coupling Through Tissue Velocity Imaging as a Bridge Between Genotyping and Phenotyping

Circ J. 2017 Dec 25;82(1):53-61. doi: 10.1253/circj.CJ-16-1279. Epub 2017 Aug 4.

Abstract

Background: Patients with Brugada syndrome (BrS) and a history of syncope or sustained ventricular arrhythmia have longer right ventricular ejection delays (RVEDs) than asymptomatic BrS patients. Different types ofSCN5Avariants leading to different reductions in sodium current (INa) may have different effects on conduction delay, and consequently on electromechanical coupling (i.e., RVED). Thus, we investigated the genotype-phenotype relationship by measuring RVED to establish whether BrS patients carrying more severeSCN5Avariants leading to premature protein truncation (T) and presumably 100%INareduction have a longer RVED than patients carrying missense variants (M) with different degrees ofINareduction.Methods and Results:There were 34 BrS patients (mean [±SD] age 43.3±12.9 years; 52.9% male) carrying anSCN5Avariant and 66 non-carriers in this cross-sectional study. Patients carrying aSCN5Avariant were divided into T-carriers (n=13) and M-carriers (n=21). Using tissue velocity imaging, RVED and left ventricular ejection delay (LVED) were measured as the time from QRS onset to the onset of the systolic ejection wave at the end of the isovolumetric contraction. T-carriers had longer RVEDs than M-carriers (139.3±15.1 vs. 124.8±11.9 ms, respectively; P=0.008) and non-carriers (127.7±17.3 ms, P=0.027). There were no differences in LVED among groups.

Conclusions: Using the simple, non-invasive echocardiographic parameter RVED revealed a more pronounced 'electromechanical' delay in BrS patients carrying T variants ofSCN5A.

Keywords: Brugada syndrome; Conduction delay; Right ventricular ejection delay; SCN5A.

MeSH terms

  • Adult
  • Brugada Syndrome / diagnostic imaging
  • Brugada Syndrome / physiopathology*
  • Codon, Nonsense
  • Cross-Sectional Studies
  • Echocardiography
  • Electrochemical Techniques
  • Female
  • Genotype
  • Heart Conduction System / diagnostic imaging
  • Heart Conduction System / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Phenotype
  • Time Factors
  • Ventricular Dysfunction, Right / diagnostic imaging
  • Ventricular Dysfunction, Right / physiopathology*

Substances

  • Codon, Nonsense
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human