title: Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome.
abstract: OBJECTIVE
  To determine the effect of epinephrine on the QT interval in patients with genotyped long QT syndrome (LQTS).
  
  
  METHODS
  Between May 1999 and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3 LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27 (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at baseline and during gradually increasing doses of intravenous epinephrine infusion (0.05, 0.1, 0.2, and 0.3 microg x k(-1) x min(-1)). The 12-lead electrocardiogram was monitored continuously, and heart rate, QT, and corrected QT interval (QTc) were measured during each study stage.
  
  
  RESULTS
  There was no significant difference in resting heart rate or chronotropic response to epinephrine between LQTS patients and controls. The mean +/- SD baseline QTc was greater in LQTS patients (500+/-68 ms) than in controls (436+/-19 ms, P<.001). However, 9 (47%) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting QTc (<460 milliseconds), whereas 11 (41%) of 27 controls had a resting QTc higher than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested prolongation of the QT interval (paradoxical response), whereas healthy controls and patients with either LQT2 or LQT3 tended to have shortened QT intervals (P<.001). The maximum mean +/- SD change in QT (AQT [epinephrine QT minus baseline QT]) was -5+/-47 ms (controls), +94+/-31 ms (LQT1), and -87+/-67 ms (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals (AQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05 microg x kg(-1) x min(-1)) completely discriminated LQT1 patients (AQT, +82+/-34 ms) from controls (AQT, -7+/-13 ms; P<.001). Epinephrine-triggered nonsustained ventricular tachycardia occurred in 2 patients with LQTS and in 1 control.
  
  
  CONCLUSIONS
  Epinephrine-induced prolongation of the QT interval appears pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus, epinephrine provocation may help unmask some patients with concealed LQTS and strategically direct molecular genetic testing.
authors: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. ackerman.michael@mayo.edu
authors: Michael J
authors: MJ
authors: Ackerman
authors: Anant
authors: A
authors: Khositseth
authors: David J
authors: DJ
authors: Tester
authors: Joseph B
authors: JB
authors: Hejlik
authors: Win-Kuang
authors: WK
authors: Shen
authors: Co-burn J
authors: CB
authors: Porter
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004305:Dose-Response Relationship, Drug; D004554:Electric Countershock; D004562:Electrocardiography / Q000187:drug effects*; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005838:Genotype; D006334:Heart Function Tests / Q000009:adverse effects / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000139:chemically induced
chemical_list: D004837:Epinephrine