title: High-rate pacing reduces variability of repolarization and prevents repolarization-dependent arrhythmias in dogs with chronic AV block.
abstract: BACKGROUND
  high-rate pacing may have an inhibitory effect on the initiation of Torsade de Pointes arrhythmias (TdP). However, permanent pacing is only indicated in high-risk patients. We performed a proof of concept study into automatic overdrive pacing for prevention of drug-induced TdP, using short-term variability of repolarization (STV) as a feedback parameter of arrhythmic risk.
  
  
  RESULTS
  the minimal signal sampling frequency required for measuring STV was determined through computer simulation. Arrhythmogenic response to dofetilide (25 microg/kg/5 minutes) was tested at two different paced heart rates (60-65 bpm vs 100-110 bpm) in 7 dogs with chronic atrioventricular block, while recording right and left ventricular (LV) monophasic action potential (MAP) and LV electrogram (EGM). Simulations showed a sampling frequency of 500 Hz is sufficient to capture relevant STV values. High-rate pacing prevented dofetilide-induced TdP seen at the low rate (low: 6/7 vs high: 1/7). At the low rate, STV from LV MAP duration increased before occurrence of spontaneous, ectopic activity and TdP (1.7 ± 0.6-3.0 ± 1.8 ms, P < 0.05), but at the high-rate STV did not change significantly (0.9 ± 0.2-1.5 ± 1.4 ms, NS). Regression analysis showed a close relation between STV calculated from LV MAP and from LV EGM (R(2) = 0.71).
  
  
  CONCLUSIONS
  high-rate pacing increases repolarization reserve in dogs with chronic atrioventricular block, preventing dofetilide-induced TdP. Changes in repolarization reserve are reflected in values of STV.
authors.affiliation: Medtronic Bakken Research Center, Maastricht, The Netherlands Medical Physiology, Division Heart & Lungs, University Medical Center Utrecht, Yalelaan 50, Utrecht, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Oosterhoff
authors.forename: Morten B
authors.initials: MB
authors.lastname: Thomsen
authors.forename: Joep N
authors.initials: JN
authors.lastname: Maas
authors.forename: Nico J M
authors.initials: NJ
authors.lastname: Atteveld
authors.forename: Jet D M
authors.initials: JD
authors.lastname: Beekman
authors.forename: Harold V M
authors.initials: HV
authors.lastname: VAN Rijen
authors.forename: Marcel A G
authors.initials: MA
authors.lastname: VAN DER Heyden
authors.forename: Marc A
authors.initials: MA
authors.lastname: Vos
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D054537:Atrioventricular Block / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D002908:Chronic Disease; D004285:Dogs; D016171:Torsades de Pointes / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*