title: SCN5A mutations in Brugada syndrome are associated with increased cardiac dimensions and reduced contractility.
abstract: BACKGROUND
  The cardiac sodium channel (Na(v)1.5) controls cardiac excitability. Accordingly, SCN5A mutations that result in loss-of-function of Na(v)1.5 are associated with various inherited arrhythmia syndromes that revolve around reduced cardiac excitability, most notably Brugada syndrome (BrS). Experimental studies have indicated that Na(v)1.5 interacts with the cytoskeleton and may also be involved in maintaining structural integrity of the heart. We aimed to determine whether clinical evidence may be obtained that Na(v)1.5 is involved in maintaining cardiac structural integrity.
  
  
  METHODS
  Using cardiac magnetic resonance (CMR) imaging, we compared right ventricular (RV) and left ventricular (LV) dimensions and ejection fractions between 40 BrS patients with SCN5A mutations (SCN5a-mut-positive) and 98 BrS patients without SCN5A mutations (SCN5a-mut-negative). We also studied 18 age/sex-matched healthy volunteers.
  
  
  RESULTS
  SCN5a-mut-positive patients had significantly larger end-diastolic and end-systolic RV and LV volumes, and lower LV ejection fractions, than SCN5a-mut-negative patients or volunteers.
  
  
  CONCLUSIONS
  Loss-of-function SCN5A mutations are associated with dilatation and impairment in contractile function of both ventricles that can be detected by CMR analysis.
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: van Hoorn
authors.forename: Maria E
authors.initials: ME
authors.lastname: Campian
authors.forename: Anje
authors.initials: A
authors.lastname: Spijkerboer
authors.forename: Marieke T
authors.initials: MT
authors.lastname: Blom
authors.forename: R Nils
authors.initials: RN
authors.lastname: Planken
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.forename: Jacques M T
authors.initials: JM
authors.lastname: de Bakker
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Maarten
authors.initials: M
authors.lastname: Groenink
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
mesh_terms: D000328:Adult; D053840:Brugada Syndrome / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009200:Myocardial Contraction / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human