Progression of atrial fibrillation from paroxysmal to permanent and the importance of specific triggers and substrate formation. In the majority of patients, atrial fibrillation is a chronically progressive arrhythmia; patients may experience asymptomatic, self-terminating episodes of the arrhythmia before atrial fibrillation is first diagnosed. Recurrences of the arrhythmia are clustered, and periods with frequent paroxysms are often alternating with longer periods without any recurrences (A). Modified with permission from Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J 2007; 28: 2803–17. Initially, atrial fibrillation can be a primary electrical disorder in response to specific triggers such as atrial premature beats, pulmonary vein tachycardia, or neurohumoral stimuli, followed by electrical, structural, and functional remodelling (B). Progression of atrial fibrillation relates to progression of the underlying disease and to continuous structural remodelling of the atria, including changes associated with ageing (e.g. fatty metamorphosis, myocyte degeneration, and fibrosis).