title: Individualized corrected QT interval is superior to QT interval corrected using the Bazett formula in predicting mutation carriage in families with long QT syndrome.
abstract: Long QT syndrome (LQTS) is characterized by reduced penetrance and variable QT prolongation over time, resulting in an estimate of 25% carriers of a pathogenic mutation with a normal corrected QT (QTc) interval on the resting electrocardiogram (ECG).
  
  
  
  The purpose of this study was to test the hypothesis that an individualized corrected QT interval derived from 24-hour Holter data more accurately predicts carriage of a pathogenic LQTS mutation than did QT derived from a standard 12-lead ECG and corrected using the Bazett formula (QTc interval).
  
  
  
  Carriers of a pathogenic LQTS mutation and their genotype-negative family members who had both resting ECG and Holter recordings available were included. Automated and manual measurements of QTc were performed. QTi was derived from 24-hour Holter recordings and defined as the QT value at the intersection of an RR interval of 1000 ms, with the linear regression line fitted through QT-RR data points of each individual patient.
  
  
  
  In total, 69 patients with LQTS (23 long QT type 1, 39 long QT type 2, and 7 long QT type 3) and 55 controls were selected. Demographic characteristics were comparable. A comparison of the receiver operating characteristic curves indicates that the test added diagnostic value compared to manual measurement (P = .02) or automated measurement (P = .005). The diagnostic accuracy of manually measured QTc using conventional cutoff criteria was 72%, while it was 92% using a sex-independent QTi cutoff of 445 ms. This was caused by a 39% increase in sensitivity without compromising the specificity.
  
  
  
  QTi derived from Holter recordings is superior to conventional QTc measured from a standard 12-lead ECG in predicting the mutation carrier state in families with LQTS.
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. Electronic address: Tomas.Robyns@uzleuven.be.
authors.forename: Tomas
authors.initials: T
authors.lastname: Robyns
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Willems
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Vandenberk
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Ector
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Garweg
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Cuno
authors.initials: C
authors.lastname: Kuiperi
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Breckpot
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Anniek
authors.initials: A
authors.lastname: Corveleyn
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Department of Cardiology, University Hospitals Antwerp, Antwerp, Belgium.
authors.forename: Hein
authors.initials: H
authors.lastname: Heidbuchel
authors.affiliation: Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Department of Cardiology, Ziekenhuis Oost Limburg Genk, Genk, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Nuyens
mesh_terms: D000328:Adult; D061827:Dimensional Measurement Accuracy; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015588:Observer Variation; D066230:Patient-Specific Modeling; D058996:Quality Improvement; D012372:ROC Curve; D015203:Reproducibility of Results
keywords: Holter; Individualized QT correction; Long QT syndrome; QT rate dependence; QT-RR relation; QTi