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.


CONCLUSIONS
Dofetilide-induced bifid T waves result from interventricular RT dispersion.
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: veromeijborg@gmail.com.
Veronique M F
VM
Meijborg
Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, New York.
Samuel
S
Chauveau
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Michiel J
MJ
Janse
Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, New York.
Evgeny P
EP
Anyukhovsky
Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, New York.
Peter R
PR
Danilo
Departments of Pharmacology and Pediatrics, Columbia University, New York, New York.
Michael R
MR
Rosen
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Tobias
T
Opthof
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands; L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France.
Ruben
R
Coronel
D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides
D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide
Bifid T wave; Dog; Long QT syndrome type 2; Repolarization