Diagnostic Accuracy of the Standing Test in Adults Suspected for Congenital Long-QT Syndrome

Background An elegant bedside provocation test has been shown to aid the diagnosis of long-QT syndrome (LQTS) in a retrospective cohort by evaluation of QT intervals and T-wave morphology changes resulting from the brief tachycardia provoked by standing. We aimed to prospectively determine the potential diagnostic value of the standing test for LQTS. Methods and Results In adults suspected for LQTS who had a standing test, the QT interval was assessed manually and automated. In addition, T-wave morphology changes were determined. A total of 167 controls and 131 genetically confirmed patients with LQTS were included. A prolonged heart rate-corrected QT interval (QTc) (men ≥430 ms, women ≥450 ms) at baseline before standing yielded a sensitivity of 61% (95% CI, 47-74) in men and 54% (95% CI, 42-66) in women, with a specificity of 90% (95% CI, 80-96) and 89% (95% CI, 81-95), respectively. In both men and women, QTc≥460 ms after standing increased sensitivity (89% [95% CI, 83-94]) but decreased specificity (49% [95% CI, 41-57]). Sensitivity further increased (P<0.01) when a prolonged baseline QTc was accompanied by a QTc≥460 ms after standing in both men (93% [95% CI, 84-98]) and women (90% [95% CI, 81-96]). However, the area under the curve did not improve. T-wave abnormalities after standing did not further increase the sensitivity or the area under the curve significantly. Conclusions Despite earlier retrospective studies, a baseline ECG and the standing test in a prospective evaluation displayed a different diagnostic profile for congenital LQTS but no unequivocal synergism or advantage. This suggests that there is markedly reduced penetrance and incomplete expression in genetically confirmed LQTS with retention of repolarization reserve in response to the brief tachycardia provoked by standing.