title: Epinephrine bolus test in detecting long QT syndrome mutation carriers with indeterminable electrocardiographic phenotype.
abstract: BACKGROUND
  In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval.
  
  
  METHODS
  Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T-wave peak-to-end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated.
  
  
  RESULTS
  Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2.
  
  
  CONCLUSIONS
  Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype-specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members.
authors.affiliation: Helsinki University Hospital, Department of Cardiology, Helsinki, Finland. anna-mari.hekkala@hel.fi
authors.forename: Anna-Mari
authors.initials: AM
authors.lastname: Hekkala
authors.forename: Heikki
authors.initials: H
authors.lastname: Swan
authors.forename: Matti
authors.initials: M
authors.lastname: Viitasalo
authors.forename: Heikki
authors.initials: H
authors.lastname: Väänänen
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
mesh_terms: D000316:Adrenergic alpha-Agonists; D000328:Adult; D000704:Analysis of Variance; D018780:Body Surface Potential Mapping; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography / Q000379:methods*; D004837:Epinephrine; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D005838:Genotype; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D000316:Adrenergic alpha-Agonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D004837:Epinephrine