Interdependence of four of the main mechanisms that contribute to the initiation and maintenance of atrial fibrillation. Each circle represents a relevant factor that may initiate or perpetuate atrial fibrillation (AF): The blue circle represents shortening of the atrial action potential and effective refractory period (electrical remodelling), the red circle focal triggers of AF, the blue circle ultrastructural changes conferred by AF (structural remodelling), and the brown circle the bidirectional damage conferred by left ventricular and (left) atrial function during AF. The pie chart within each circle gives educated guesses as to how often this pathophysiological mechanism will be due to AF itself (black pie piece), genetic predispositions (light blue), a response of the atria to stressors such as hypertension, diabetes, or valvular heart disease (grey), and ageing (light green). In an individual patient (but also in a specific experimental model), AF will be due to a blend of these different factors as indicated by the blended overlap between the circles. Reproduced with permission from .