Atrial remodeling, fibrosis, and atrial fibrillation

Trends Cardiovasc Med. 2015 Aug;25(6):475-84. doi: 10.1016/j.tcm.2014.12.015. Epub 2014 Dec 31.


The fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological, and inflammation changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs, and myofibroblast activation are all thought to be involved in AF-induced atrial remodeling. However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Here we postulate a working model that might open new pathways for future investigation into mechanisms of AF perpetuation. We start from the premise that the progression to AF perpetuation is the result of interplay among manifold signaling pathways with differing kinetics. Some such pathways have relatively fast kinetics (e.g., oxidative stress-mediated shortening of refractory period); others likely depend on molecular processes with slower kinetics (e.g., transcriptional changes in myocyte ion channel protein expression mediated through inflammation and fibroblast activation). We stress the need to fully understand the relationships among such pathways should one hope to identify novel, truly effective targets for AF therapy and prevention.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Arrhythmia Agents / therapeutic use
  • Atrial Fibrillation / physiopathology*
  • Atrial Fibrillation / therapy*
  • Atrial Remodeling / physiology*
  • Catheter Ablation / methods
  • Electrophysiological Phenomena
  • Female
  • Fibrosis / pathology
  • Fibrosis / physiopathology
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Oxidative Stress / physiology
  • Prognosis
  • Reactive Oxygen Species / metabolism*
  • Recurrence
  • Risk Assessment
  • Severity of Illness Index
  • Signal Transduction


  • Anti-Arrhythmia Agents
  • MicroRNAs
  • Reactive Oxygen Species