Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS3. The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene.
Methods: The study group consisted of 101 adult family members: 57 carriers and 44 noncarriers (mean age 44.6 +/- 14.6 and 40.3 +/- 12.8 years, respectively). In all individuals a 12-lead ECG, exercise ECG, and 24-hour Holter ECG were obtained.
Results: Correction for heart rate significantly improved the diagnostic performance of the QT interval. Diagnostic performance of the Bazett formula was similar to that of the newer formulas (Fridericia, Hodges, Framingham, and a logarithmic formula). At a cut-off value of 440 ms, the Bazett corrected QT interval was associated with a sensitivity and specificity of 90% and 91%, respectively. Using the 24-hour Holter ECG, a prolonged QTc at heart rates less than 60 beats/min was almost pathognomonic for genetic mutation (sensitivity and specificity both 99%), whereas the QTc calculated at the lowest heart rate using Bazett's formula provided full discrimination.
Conclusion: In the present family, the resting ECG gave a good indication about the presence or absence of genetic mutation but a 24-hour Holter recording was mandatory to ascertain the diagnosis. In the diagnosis of this form of LQTS3, Bazett's formula was at least as good as other proposed corrections of the QT interval to heart rate.