folder

Arrhythmogenic remodeling of the left ventricle in a porcine model of repaired tetralogy of fallot

Authors

  • V. Dubes
  • D. Benoist
  • F. Roubertie
  • S.H. Gilbert
  • M. Constantin
  • S. Charron
  • D. Elbes
  • D. Vieillot
  • B. Quesson
  • H. Cochet
  • M. Haïssaguerre
  • C. Rooryck
  • P. Bordachar
  • J.B. Thambo
  • O. Bernus

Journal

  • Circulation Arrhythmia and Electrophysiology

Citation

  • Circ Arrhythm Electrophysiol 11 (10): e006059

Abstract

  • BACKGROUND: Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae. METHODS: Piglets underwent a tetralogy of Fallot repair-like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot. RESULTS: Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols. CONCLUSIONS: We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.


DOI

doi:10.1161/CIRCEP.117.006059