Electrophysiological Consequences of Cardiac Fibrosis

Sander Verheule*, Ulrich Schotten

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an increased amount of fibrous tissue. However, fibrosis is not a singular entity. Various forms can be distinguished, that differ in distribution: replacement fibrosis, endomysial and perimysial fibrosis, and perivascular, endocardial, and epicardial fibrosis. These different forms typically result from diverging pathophysiological mechanisms and can have different consequences for conduction. The impact of fibrosis on propagation depends on exactly how the patterns of electrical connections between myocytes are altered. We will therefore first consider the normal patterns of electrical connections and their regional diversity as determinants of propagation. Subsequently, we will summarize current knowledge on how different forms of fibrosis lead to a loss of electrical connectivity in order to explain their effects on propagation and mechanisms of arrhythmogenesis, including ectopy, reentry, and alternans. Finally, we will discuss a histological quantification of fibrosis. Because of the different forms of fibrosis and their diverging effects on electrical propagation, the total amount of fibrosis is a poor indicator for the effect on conduction. Ideally, an assessment of cardiac fibrosis should exclude fibrous tissue that does not affect conduction and differentiate between the various types that do; in this article, we highlight practical solutions for histological analysis that meet these requirements.

Original languageEnglish
Article number3220
Number of pages19
JournalCells
Volume10
Issue number11
DOIs
Publication statusPublished - 18 Nov 2021

Keywords

  • 2-DIMENSIONAL SHEET
  • ANISOTROPIC PROPAGATION
  • ATRIAL-FIBRILLATION SUBSTRATE
  • Animals
  • CELL-SIZE
  • CONDUCTION-VELOCITY
  • Confounding Factors, Epidemiologic
  • Disease Models, Animal
  • ELECTRICAL-ACTIVITY
  • Electrophysiological Phenomena
  • Fibrosis
  • HEART-FAILURE
  • Heart Conduction System/physiopathology
  • Humans
  • MAGNETIC-RESONANCE
  • Myocardium/pathology
  • POSTERIOR LEFT ATRIUM
  • VENTRICULAR-TACHYCARDIA
  • arrhythmias
  • conduction
  • fibrosis
  • heart
  • tissue structure

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