title: Gene-specific differences in the circadian variation of ventricular repolarization in the long QT syndrome: a key to sudden death during sleep?
abstract: BACKGROUND
  In the long QT syndrome (LQTS) most life-threatening cardiac events occur in association with physical or emotional stress. However, a minority of patients dies suddenly during sleep; intriguingly, these sleep-related sudden deaths tend to cluster in families. The mechanism(s) underlying this phenomenon and the reason why it occurs in few selected families are unknown. Recently, some of the LQTS genes have been identified leading to three main subgroups (LQT1, LQT2, LQT3) associated respectively with mutations affecting the following ionic currents involved in the control of ventricular repolarization: I(Ks), I(Kr), I(Na). We have recently observed that cardiac events nighttime are rare in LQT1 and frequent in LQT3 patients.
  
  
  METHODS
  We studied 26 LQTS patients all genotyped (11 LQT1, 9 LQT2, 6 LQT3) and 26 healthy controls matched by age and gender. Using a specific software, 24-hour ambulatory ECG recordings were performed and the QT interval was measured in order to allow comparison between QTc nighttime and daytime.
  
  
  RESULTS
  The main finding is that while LQT1 patients show a trend for modest QTc shortening and LQT2 patients a trend for modest lengthening nighttime versus daytime, LQT3 patients show clear lengthening of the QTc nighttime. These changes are not explained by heart rate changes or by the use of beta-blockers.
  
  
  CONCLUSIONS
  The marked tendency for further QT prolongation nighttime, which clearly increases arrhythmic risk, present among LQT3 patients and absent among LQT1 patients, provides an explanation for the gene-specific higher risk for sudden death during sleep for LQT3 compared to LQT1 patients.
authors.affiliation: Pediatric Arrhythmias Center, Istituto Auxologico Italiano IRCCS, Milan.
authors.forename: M
authors.initials: M
authors.lastname: Stramba-Badiale
authors.forename: S G
authors.initials: SG
authors.lastname: Priori
authors.forename: C
authors.initials: C
authors.lastname: Napolitano
authors.forename: E H
authors.initials: EH
authors.lastname: Locati
authors.forename: X
authors.initials: X
authors.lastname: Viñolas
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
authors.forename: E
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: K
authors.initials: K
authors.lastname: Goulene
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012890:Sleep / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics
chemical_list: D015222:Sodium Channels