Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome : Diagnostic accuracy of the paradoxical QT response

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-03, Vol.113 (11), p.1385-1392
• Main Authors: VYAS, Himeshkumar, HEJLIK, Joseph, ACKERMAN, Michael J
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenergic Agents - pharmacology; Adrenergic Agents - therapeutic use; Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adult; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Child; Cohort Studies; Diseases of the lymphatic vessels; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Electrocardiography - drug effects; Epinephrine - pharmacology; Exercise Test - methods; Female; General and cellular metabolism. Vitamins; Humans; KCNQ1 Potassium Channel - deficiency; KCNQ1 Potassium Channel - genetics; Long QT Syndrome - diagnosis; Long QT Syndrome - drug therapy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Predictive Value of Tests; Retrospective Studies; Romano-Ward Syndrome - diagnosis; Romano-Ward Syndrome - drug therapy; Romano-Ward Syndrome - genetics; Sensitivity and Specificity
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.600445

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). 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