Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction

Ali Gharaviri, Sander Verheule, Jens Eckstein, Mark Potse, Rolf Krause, Angelo Auricchio, Nico H. L. Kuijpers, Ulrich Schotten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Aims Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood. We hypothesized that structural remodelling may explain this reduced efficacy by making the substrate more three-dimensional. To investigate this, we simulated the effect of sodium (Nathorn)-channel block on AF in a model of progressive transmural uncoupling. Methods and results In a computer model consisting of two cross-connected atrial layers, with realistic atrial membrane behaviour, structural remodelling was simulated by reducing the number of connections between the layers. 100% of endoepicardial connectivity represented a healthy atrium. At various degrees of structural remodelling, we assessed the effect of 60% sodium channel block on AF stability, endo-epicardial electrical activity dissociation (EED), and fibrillatory conduction pattern complexity quantified by number of waves, phase singularities (PSs), and transmural conduction ('breakthrough', BT). Sodium channel block terminated AF in non-remodelled but not in remodelled atria. The temporal excitable gap (EG) and AF cycle length increased at all degrees of remodelling when compared with control. Despite an increase of EED and EG, sodium channel block decreased the incidence of BT because of transmural conduction block. Sodium channel block decreased the number of waves and PSs in normal atrium but not in structurally remodelled atrium. Conclusion This simple atrial model explains the loss of efficacy of sodium channel blockers in terminating AF in the presence of severe structural remodelling as has been observed experimentally and clinically. Atrial fibrillation termination in atria with moderate structural remodelling in the presence of sodium channel block is caused by reduction of AF complexity. With more severe structural remodelling, sodium channel block fails to promote synchronization of the two layers of the model.
Original languageEnglish
Pages (from-to)iii69-iii76
Number of pages8
JournalEP Europace
Volume20
Issue numberSuppl. 3
DOIs
Publication statusPublished - 1 Nov 2018
Event9th Theo Rossi di Montelera (TRM) Forum on Computer Simulation and Experimental Assessment of Cardiac Function: From Model to Clinical Outcome - Ctr Computat Med Cardiol, Lugano, SWITZERLAND, Lugano, Switzerland
Duration: 4 Dec 20175 Dec 2017

Keywords

  • Atrial fibrillation
  • Three-dimensional
  • Computer model
  • Transmural conduction
  • Electrical dissociation
  • Sodium-channel block
  • SINUS RHYTHM
  • FLECAINIDE
  • PERSISTENT
  • MECHANISMS
  • CARDIOVERSION
  • TERMINATION
  • CONVERSION
  • INSIGHTS

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