title: Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.
abstract: BACKGROUND
  Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.
  
  
  OBJECTIVE
  In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.
  
  
  METHODS
  The electrical activity of human transmural ventricular tissue (5 cm × 5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation.
  
  
  RESULTS
  No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.
  
  
  CONCLUSIONS
  Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.
authors: Instituto de Investigación en Ingeniería Biomédica, UniversitatPolitècnica de València, Valencia, Spain.
authors: Juan F
authors: JF
authors: Gomez
authors: Instituto de Investigación en Ingeniería Biomédica, UniversitatPolitècnica de València, Valencia, Spain.
authors: Karen
authors: K
authors: Cardona
authors: Instituto de Investigación en Ingeniería Biomédica, UniversitatPolitècnica de València, Valencia, Spain.
authors: Laura
authors: L
authors: Martinez
authors: Instituto de Investigación en Ingeniería Biomédica, UniversitatPolitècnica de València, Valencia, Spain.
authors: Javier
authors: J
authors: Saiz
authors: Instituto de Investigación en Ingeniería Biomédica, UniversitatPolitècnica de València, Valencia, Spain.
authors: Beatriz
authors: B
authors: Trenor
mesh_terms: D003198:Computer Simulation; D055724:Electrophysiological Phenomena; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular; D009206:Myocardium / Q000473:pathology