Interventricular dispersion in repolarization causes bifid T waves in dogs with dofetilide-induced long QT syndrome

Background Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. Objective The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. Methods We simultaneously recorded surface ECG and unipolar electrograms at baseline and after dofetilide in a canine model of dofetilide-induced LQT2 (6 male mongrel dogs). Standard ECG variables, T-wave duration, and moments of peaks of bifid T waves (Tp1 and Tp2) were correlated with moments of local repolarization. Epicardial electrograms were recorded over the left ventricular (LV) and right ventricular (RV) anterior walls (11 × 11 electrode grid, 5-mm interelectrode distance). In 5 of the 6 hearts, we also recorded intramural unipolar electrograms (n = 4–7 needles per heart). In each unipolar recording, we determined activation time, repolarization time (RTs), and activation–recovery interval. In addition, we studied RT response to heart rate changes. Results Dofetilide prolonged QT and QTc, induced bifid T waves in 4 of 6 animals, and prolonged RT heterogeneously in LV and RV, resulting in increased interventricular and LV intraventricular RT dispersion. Dofetilide did not induce a disparate response in activation–recovery interval across the transmural axis. Dofetilide-induced separation of RT across the RV–LV interface concurred with the moments of T-wave peaks. Dofetilide-induced steepening of restitution slopes was larger in LV than RV. Conclusion Dofetilide-induced bifid T waves result from interventricular RT dispersion.