Ion channel dysfunction and fibrosis in atrial fibrillation: Two sides of the same coin

Background: Atrial fibrillation (AF) is a common heart rhythm disorder that is associated with an increased risk of stroke and heart failure (HF). Initially, an association between AF and ion channel dysfunction was identified, classifying the pathology as a predominantly electrical disease. More recently it has been recognized that fibrosis and structural atrial remodeling play a driving role in the development of this arrhythmia also in these cases. Purpose: Understanding the role of fibrosis in genetic determined AF could be important to better comprise the pathophysiology of this arrhythmia and to refine its management also in nongenetic forms. In this review we analyze genetic and epigenetic mechanisms responsible for AF and their link with atrial fibrosis, then we will consider analogies with the pathophysiological mechanism in nongenetic AF, and discuss consequent therapeutic options.