Individualized corrected QT interval is superior to QT interval corrected using the Bazett formula in predicting mutation carriage in families with long QT syndrome

Heart Rhythm. 2017 Mar;14(3):376-382. doi: 10.1016/j.hrthm.2016.11.034.


Background: 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).

Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Holter; Individualized QT correction; Long QT syndrome; QT rate dependence; QT-RR relation; QTi.

MeSH terms

  • Adult
  • Dimensional Measurement Accuracy*
  • Electrocardiography, Ambulatory / methods*
  • Female
  • Genotype
  • Heart Rate
  • Humans
  • Long QT Syndrome* / diagnosis
  • Long QT Syndrome* / genetics
  • Long QT Syndrome* / physiopathology
  • Male
  • Middle Aged
  • Mutation
  • Observer Variation
  • Patient-Specific Modeling
  • Quality Improvement
  • ROC Curve
  • Reproducibility of Results