title: The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.
abstract: BACKGROUND
  Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction.
  
  
  RESULTS
  Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers.
  
  
  CONCLUSIONS
  This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Sun
authors.forename: Jason I
authors.initials: JI
authors.lastname: Koontz
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Kent R
authors.initials: KR
authors.lastname: Nilsson
authors.forename: Damian
authors.initials: D
authors.lastname: Craig
authors.forename: Carol
authors.initials: C
authors.lastname: Haynes
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Hranitzky
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Pitt
mesh_terms: D001741:Black or African American; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D016757:Death, Sudden, Cardiac / Q000208:ethnology / Q000517:prevention & control; D017147:Defibrillators, Implantable; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000208:ethnology / Q000235:genetics / Q000628:therapy*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels