title: Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome.
abstract: OBJECTIVE
  This study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers.
  
  
  BACKGROUND
  The LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance.
  
  
  METHODS
  The 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV).
  
  
  RESULTS
  The mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients.
  
  
  CONCLUSIONS
  Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. wshimizu@hsp.ncvc.go.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Noda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurita
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Satomi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suyama
authors.forename: Naohiko
authors.initials: N
authors.lastname: Aihara
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Echigo
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004562:Electrocardiography / Q000187:drug effects*; D004837:Epinephrine; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects* / Q000235:genetics*; D011930:Reaction Time / Q000187:drug effects* / Q000235:genetics*; D015203:Reproducibility of Results; D029597:Romano-Ward Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D012680:Sensitivity and Specificity; D013566:Sympathomimetics
chemical_list: D013566:Sympathomimetics; D004837:Epinephrine