title: Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome.
abstract: 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.
  
  
  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.
authors.affiliation: The Children's Hospital of Philadelphia, Division of Cardiology, and University of Pennsylvania School of Medicine, Philadelphia, PA, USA. aziz@email.chop.edu
authors.forename: Peter F
authors.initials: PF
authors.lastname: Aziz
authors.forename: Tammy S
authors.initials: TS
authors.lastname: Wieand
authors.forename: Jamie
authors.initials: J
authors.lastname: Ganley
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Henderson
authors.forename: Akash R
authors.initials: AR
authors.lastname: Patel
authors.forename: V Ramesh
authors.initials: VR
authors.lastname: Iyer
authors.forename: R Lee
authors.initials: RL
authors.lastname: Vogel
authors.forename: Michael
authors.initials: M
authors.lastname: McBride
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Vetter
authors.forename: Maully J
authors.initials: MJ
authors.lastname: Shah
mesh_terms: D000222:Adaptation, Physiological; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D015444:Exercise; D005080:Exercise Test; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015143:Philadelphia; D011187:Posture; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011237:Predictive Value of Tests; D020127:Recovery of Function; D012189:Retrospective Studies; D029597:Romano-Ward Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels