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Deleterious acute and chronic effects of bradycardic right ventricular apex pacing: consequences for arrhythmic outcome

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Abstract

In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min. ECG, and left (LV) and right ventricular (RV) monophasic action potentials durations (MAPD) were recorded; activation time (AT) and activation recovery interval (ARI) were determined from ten distinct LV electrograms; interventricular mechanical delay (IVMD) and time-to-peak strain (TTP) of the LV septal and lateral wall (ΔTTP: lateral wall minus septal wall) were obtained echocardiographically. Dofetilide (25 μg/kg/5 min) was infused to study TdP inducibility. In baseline AAVB, in comparison to SR, RVA bradypacing acutely increased QT interval, LV, and RVMAPD. Echocardiographic IVMD and ΔTTP were initially increased, which was partially corrected after 3 weeks of RVA pacing (IVMD: 22 ± 13 vs. 42 ± 11 vs. 31 ± 6 ms; ΔTTP: −2 ± 47 vs. −114 ± 38 vs. −36 ± 22 ms). QT interval (362 ± 23 vs. 373 ± 29 ms), LVMAPD (245 ± 18 vs. 253 ± 22 ms), RVMAPD (226 ± 26 vs. 238 ± 31 ms), and mean LV-ARI (268 ± 5 vs. 267 ± 6 ms) were not significantly changed after 3 weeks of RVA pacing. During AAVB, dofetilide increased mean LV-ARI (381 ± 11 ms) with largest increases in the later activated basal areas (slope AT-ARI: +0.96). In contrast with acute RVA pacing, 3 week pacing increased TdP inducibility (0/13 vs. 11/21) and mean LV-ARI (484 ± 18 ms), while the slope of AT-ARI responded differently on dofetilide (−2.37), with larger APD increases in the early region. The latter was supported at the molecular level: reduced RNA expressions of three repolarization-related ion channel genes in early (KCNQ1, KCNH2, and KCNJ2) versus two in late regions (KNCQ1 and KCNJ2). In conclusion, bradycardic RVA pacing acutely induced LV intra- and interventricular mechanical dyssynchrony, which was partially reversed after 3 weeks of pacing (remodeling). The latter occurred without apparent baseline electrical effects. However, dofetilide clearly unmasked (region-specific) arrhythmic consequences of remodeling.

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Acknowledgements

The authors would like to thank Dr. P. Oosterhoff for the custom-written MATLAB software, Medtronic for providing the pacemakers, St. Jude Medical Netherlands for providing the duo-decapolar catheters, and Mrs. A. Gohar for language editing. This research was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project COHFAR (Grant No. 01C-203), and supported by the Dutch Heart Foundation.

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  1. T. R. G. Stams and A. Dunnink contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands

    T. R. G. Stams, A. Dunnink, H. D. M. Beekman, R. van der Nagel, B. Kok, M. F. A. Bierhuizen & M. A. Vos

  2. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

    W. M. van Everdingen, M. J. Cramer & M. Meine

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  1. T. R. G. Stams
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Stams, T.R.G., Dunnink, A., van Everdingen, W.M. et al. Deleterious acute and chronic effects of bradycardic right ventricular apex pacing: consequences for arrhythmic outcome. Basic Res Cardiol 112, 46 (2017). https://doi.org/10.1007/s00395-017-0636-z

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