Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome

Am J Physiol Heart Circ Physiol. 2024 Jun 1;326(6):H1350-H1365. doi: 10.1152/ajpheart.00004.2024. Epub 2024 Mar 29.

Abstract

Premature ventricular complexes (PVCs) are spontaneous excitations occurring in the ventricles of the heart that are associated with ventricular arrhythmias and sudden cardiac death. Under long QT conditions, PVCs can be mediated by repolarization gradient (RG) and early afterdepolarizations (EADs), yet the effects of heterogeneities or geometry of the RG or EAD regions on PVC genesis remain incompletely understood. In this study, we use computer simulation to systematically investigate the effects of the curvature of the RG border region on PVC genesis under long QT conditions. We show that PVCs can be either promoted or suppressed by negative or positive RG border curvature depending on the source and sink conditions. When the origin of oscillation is in the source region and the source is too strong, a positive RG border curvature can promote PVCs by causing the source area to oscillate. When the origin of oscillation is in the sink region, a negative RG border curvature can promote PVCs by causing the sink area to oscillate. Furthermore, EAD-mediated PVCs are also promoted by negative border curvature. We also investigate the effects of wavefront curvature and show that PVCs are promoted by convex but suppressed by concave wavefronts; however, the effect of wavefront curvature is much smaller than that of RG border curvature. In conclusion, besides the increase of RG and occurrence of EADs caused by QT prolongation, the geometry of the RG border plays important roles in PVC genesis, which can greatly increase the risk of arrhythmias in cardiac diseases.NEW & NOTEWORTHY The effects of the curvature or geometry of the repolarization gradient region and wavefront curvature on the genesis of premature ventricular complexes are systematically investigated using computer modeling and simulation. Premature ventricular complexes can be promoted by either positive or negative curvature of the gradient region depending on the source and sink conditions. The underlying mechanisms of the curvature effects are revealed, which provides mechanistic insights into arrhythmogenesis in cardiac diseases.

Keywords: curvature; early afterdepolarization; long QT syndrome; premature ventricular complex; repolarization gradient.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Computer Simulation*
  • Heart Conduction System / physiopathology
  • Heart Rate
  • Heart Ventricles / physiopathology
  • Humans
  • Long QT Syndrome* / physiopathology
  • Models, Cardiovascular*
  • Ventricular Premature Complexes* / physiopathology