The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction

Albert Y. Sun, Jason I. Koontz, Svati H. Shah, Jonathan P. Piccini, Kent R Nilsson, Damian Craig, Carol Haynes, Simon G. Gregory, Patrick M. Hranitzky, Geoffrey S. Pitt

Research output: Contribution to journalArticle

27 Citations (Scopus)

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. Methods and 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 antitachycardia 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.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalCirculation: Cardiovascular Genetics
Volume4
Issue number2
DOIs
StatePublished - Apr 1 2011

Fingerprint

Implantable Defibrillators
Sodium Channels
Heart Failure
Primary Prevention
Cardiac Arrhythmias
Electrophysiology
Sudden Cardiac Death
Incidence
Ventricular Fibrillation
Ventricular Tachycardia
Proportional Hazards Models
Shock
Therapeutics
Alleles
Clinical Trials
Confidence Intervals
Mortality

Keywords

  • Death
  • Genetics
  • Heart failuR.E.
  • Ion channels
  • Race/ethnicity
  • Sudden

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction. / Sun, Albert Y.; Koontz, Jason I.; Shah, Svati H.; Piccini, Jonathan P.; Nilsson, Kent R; Craig, Damian; Haynes, Carol; Gregory, Simon G.; Hranitzky, Patrick M.; Pitt, Geoffrey S.

In: Circulation: Cardiovascular Genetics, Vol. 4, No. 2, 01.04.2011, p. 163-168.

Research output: Contribution to journalArticle

Sun, Albert Y. ; Koontz, Jason I. ; Shah, Svati H. ; Piccini, Jonathan P. ; Nilsson, Kent R ; Craig, Damian ; Haynes, Carol ; Gregory, Simon G. ; Hranitzky, Patrick M. ; Pitt, Geoffrey S. / The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction. In: Circulation: Cardiovascular Genetics. 2011 ; Vol. 4, No. 2. pp. 163-168.
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