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Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

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Item Type:Article
Title:Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot
Creators Name:Benoist, D. and Dubes, V. and Roubertie, F. and Gilbert, S.H. and Charron, S. and Constantin, M. and Elbes, D. and Vieillot, D. and Quesson, B. and Cochet, H. and Haissaguerre, M. and Rooryck, C. and Bordachar, P. and Thambo, J.B. and Bernus, O.
Abstract:OBJECTIVE: The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF). METHODS AND RESULTS: Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV. CONCLUSION: Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.
Keywords:Action Potentials, Animal Disease Models, Cardiac Arrhythmias, Cardiac Surgical Procedures, Connexin 43, Heart Conduction System, Heart Rate, Magnetic Resonance Imaging, Right Ventricular Function, Shal Potassium Channels, Tetralogy of Fallot, Time Factors, Ventricular Remodeling, Voltage-Sensitive Dye Imaging, Animals, Sus scrofa
Publisher:BMJ Publishing Group
Page Range:347-354
Date:March 2017
Official Publication:https://doi.org/10.1136/heartjnl-2016-309730
PubMed:View item in PubMed

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