Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome.

Background: Exercise stress testing has shown diagnostic utility in adult patients with long-QT syndrome (LQTS); however, the QT interval adaptation in response to exercise in pediatric patients with LQTS has received little attention.

Methods And Results: One-hundred fifty-eight patients were divided into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal control subjects without cardiovascular disease. Each patient underwent a uniform exercise protocol with a cycle ergometer followed by a 9-minute recovery phase with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG while resting in the supine position and in a standstill position during continuous ECG recording to determine changes in the QT and RR intervals. Fifty patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the control group consisted of 108 patients. QT interval adaptation was abnormal in the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1 or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91% positive predictive value. A recovery ΔQTc((7 min-1 min)) >30 ms predicted LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive predictive value. The postural ΔQT was significantly different between LQTS and control groups (P=0.005).

Conclusions: Genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS. An extended recovery phase is preferable to assess the repolarization response after exercise in the pediatric population.