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PRECLINICAL STUDY

High-Septal Pacing Reduces Ventricular Electrical Remodeling and Proarrhythmia in Chronic Atrioventricular Block Dogs

Stephan K.G. Winckels, MD^_*,3,_*, Morten B. Thomsen, PhD^_*,3, Peter Oosterhoff, MSc^_*,,1,2, Avram Oros, MD^_*, Jet D.M. Beekman^_*, Nico J.M. Attevelt^_*, Leo Kretzers, MSc^,2 and Marc A. Vos, PhD^_*

^_* Department of Medical Physiology, Heart Lung Center Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands
Bakken Research Center, Medtronic, Maastricht, the Netherlands.

Manuscript received February 16, 2007; revised manuscript received May 9, 2007, accepted May 14, 2007.

^_* Reprint requests and correspondence: Dr. Stephan K. G. Winckels, Department of Medical Physiology, Heart Lung Center Utrecht, UMC Utrecht, Yalelaan 50, 3584 CM Utrecht, the Netherlands. (Email: s.k.g.winckels{at}umcutrecht.nl).

Objectives: This study was designed to analyze the relevance of ventricular activation patterns for ventricular electrical remodeling after atrioventricular (AV) block in dogs.

Background: Bradycardia is thought to be the main contributor to ventricular electrical remodeling after complete AV block. However, an altered ventricular activation pattern or AV dyssynchrony may also contribute.

Methods: For 4 weeks, AV block dogs were either paced from the high-ventricular septum near the His bundle at lowest captured rate (n = 9, high-septal pacing [HSP]) or kept at idioventricular rate without controlled activation (n = 14, chronic AV block [CAVB]). Multiple electrocardiographic and electrophysiological parameters were measured under anesthesia at 0 and 4 weeks. Proarrhythmia was tested at 4 weeks by I_Kr block (25 µg/kg dofetilide intravenous).

Results: At 0 weeks, the 2 groups were comparable, whereas after 4 weeks of similar bradycardia, QT duration at unpaced conditions had increased from 300 ± 5 to 395 ± 18 ms in CAVB (+32 ± 6%) and from 307 ± 8 ms to 357 ± 11 ms in HSP (+17 ± 4%; p < 0.05). Frequency dependency of repolarization was less steep in HSP compared to CAVB dogs after 4 weeks remodeling. Beat-to-beat variability of repolarization, a proarrhythmic parameter, increased only in CAVB from 0 to 4 weeks. Torsades de pointes arrhythmias were induced at 4 weeks in 44% HSP versus 78% CAVB dogs (p = 0.17). Cumulative duration of arrhythmias per inducible dog was 87 ± 36 s in CAVB and 30 ± 21 s in HSP (p < 0.05).

Conclusions: High-septal pacing reduces the magnitude of ventricular electrical remodeling and proarrhythmia in AV block dogs, suggesting a larger role for altered ventricular activation pattern in the generation of ventricular electrical remodeling than previously assumed.

Abbreviations and Acronyms   AT = activation time   (C)AVB = (chronic) atrioventricular block   ECG = electrocardiogram   HSP = high-septal pacing   IVR = idioventricular rhythm   LV = left ventricle/ventricular   MAP(D) = monophasic action potential (duration)   MAPD = interventricular dispersion of monophasic action potential duration   RV = right ventricle/ventricular   STV = short-term beat-to-beat variability of left ventricular monophasic action potential duration   TdP = torsades de pointes

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