title: Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome.
abstract: BACKGROUND
  The QTc interval prolongation is not a perfect surrogate marker of the presence of an increased risk for arrhythmic events. In the search for alternative markers, we investigated the T-amplitude and QT interval adaptation to heart rate (HR) in patients with the congenital long QT syndrome (LQTS) and individuals with sotalol-induced QT prolongation.
  
  
  RESULTS
  Our investigation is based on the analysis of continuous 12-lead digital Holter recordings in: 49 LQT1 carriers, 25 LQT2 carriers, 37 healthy individuals off drugs and on 160 mg of sotalol, and 21 of them also on 320 mg of sotalol. The Holter recordings were used to investigate repolarization parameters and their HR dependency. A loss of HR dependency of the T-amplitude was found as a common feature in individuals with impaired I(kr) kinetics: LQT2 carriers and subjects on sotalol. The T-amplitude/RR slope was significantly (P < 0.05) flatter in LQT2 (0.31 +/- 0.27 microV/ms) than in both LQT1 (0.62 +/- 0.40 microV/ms) and healthy individuals (0.55 +/- 0.29 microV/ms). A dose-dependent reduction of the T-amplitude/RR slope was also observed in subjects on sotalol (160 mg dose: 0.26 +/- 0.19 microV/ms; 320 mg dose: 0.21 +/- 0.14 microV/ms). The QT/RR slope was less effective than T-amplitude/RR slope in differentiating between congenital and drug-induced repolarization delay.
  
  
  CONCLUSIONS
  Impaired adaptation of T-amplitude to changing HR is a common electrocardiographic feature associated with KCNH2 mutation and I(kr) blockade by sotalol. This ECG marker may play an important role in the future of the assessment of the penetrance of KCNH2 mutation and the identification of a drug effect on the I(kr) kinetics.
authors.affiliation: Heart Research Follow-Up Program, Cardiology Department, University of Rochester Medical Center, Rochester, New York, USA. jean-philippe.couderc@heart.rochester.edu
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Couderc
authors.forename: Martino
authors.initials: M
authors.lastname: Vaglio
authors.forename: Xiajuan
authors.initials: X
authors.lastname: Xia
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Pierre
authors.initials: P
authors.lastname: Wicker
authors.forename: Nenad
authors.initials: N
authors.lastname: Sarapa
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
mesh_terms: D000328:Adult; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D000072237:ERG1 Potassium Channel; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006339:Heart Rate; D006801:Humans; D008133:Long QT Syndrome / Q000151:congenital* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human