Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response.
BACKGROUND
A paradoxical increase in the uncorrected QT interval during infusion of low-dose epinephrine appears pathognomonic for type 1 long-QT syndrome (LQT1). We sought to determine the diagnostic accuracy of this response among patients referred for clinical evaluation of congenital long-QT syndrome (LQTS).


RESULTS
From 1999 to 2002, 147 genotyped patients (125 untreated and 22 undergoing beta-blocker therapy) had an epinephrine QT stress test that involved a 25-minute infusion protocol (0.025 to 0.3 microg.kg(-1).min(-1)). A 12-lead ECG was monitored continuously, and repolarization parameters were measured. The sensitivity, specificity, and positive and negative predictive values for the paradoxical QT response (defined as a > or =30-ms increase in QT during infusion of < or =0.1 microg.kg(-1).min(-1) epinephrine) was determined. The 125 untreated patients (44 genotype negative, 40 LQT1, 30 LQT2, and 11 LQT3) constituted the primary analysis. The median baseline corrected QT intervals (QTc) were 444 ms (gene negative), 456 ms (LQT1), 486 ms (LQT2), and 473 ms (LQT3). The median change in QT interval during low-dose epinephrine infusion was -23 ms in the gene-negative group, 78 ms in LQT1, -4 ms in LQT2, and -58 ms in LQT3. The paradoxical QT response was observed in 37 (92%) of 40 patients with LQT1 compared with 18% (gene-negative), 13% (LQT2), and 0% (LQT3; P<0.0001) of the remaining patients. Overall, the paradoxical QT response had a sensitivity of 92.5%, specificity of 86%, positive predictive value of 76%, and negative predictive value of 96% for LQT1 status. Secondary analysis of the subset undergoing beta-blocker therapy indicated inferior diagnostic utility in this setting.


CONCLUSIONS
The epinephrine QT stress test can unmask concealed type 1 LQTS with a high level of accuracy.
Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
Himeshkumar
H
Vyas
Joseph
J
Hejlik
Michael J
MJ
Ackerman
D000293:Adolescent; D018663:Adrenergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000172:deficiency / Q000235:genetics; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D029597:Romano-Ward Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D012680:Sensitivity and Specificity
D018663:Adrenergic Agents; D000319:Adrenergic beta-Antagonists; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D004837:Epinephrine