When the Clock Strikes A-fib

Within the broad spectrum of atrial fibrillation (AF) symptomatology, there is a striking subset of patients with predominant or even solitary nocturnal onset of the arrhythmia. This review covers AF with nocturnal onset, with the aim of defining this distinctive subgroup among patients with AF. A periodicity analysis is provided showing a clear increased onset between 10:00 pm and 7:00 am. Multiple interacting mechanisms are discussed, such as circadian modulation of electrophysiological properties, vagal tone, and sleep disorders, as well as the potential interaction and synergism between these factors, to provide a better understanding of this clinical entity. Lastly, potential therapeutic targets for AF with nocturnal onset are addressed such as upstream therapy for underlying comorbidities, type of drug and timing of drug administration and pulmonary vein isolation, ablation of the ganglionated plexus, and autonomic nervous system modulation. Understanding the underlying AF mechanisms in the individual patient with nocturnal onset will contribute to patient-specific therapy. [Display omitted] •The onset of AF is most often nocturnal in patients with paroxysmal and persistent AF, whereas one-quarter of patients have a solely nocturnal onset of AF.•Be aware of the potential presence of nocturnal AF in the individual patient.•Specific history taking and diagnostic workup are recommended to identify and characterize potential contributors to nocturnal AF. This should include a low threshold for sleep testing to assess presence of OSA and possibly other sleep disorders. Inquiries should be made about excessive exercise and (binge) drinking as well as body position during sleep and presence of GERD.•Comorbidity treatment and lifestyle optimization should be a part of AF therapy. In AF with nocturnal onset OSA diagnosis and treatment, and a reduction in alcohol consumption before sleep onset are best supported by clinical evidence. Body position therapy and proton-pump inhibitors may be considered in some specific patients, although clinical evidence is lacking.•Based on the pharmacologic profile, vagolytic drugs such as flecainide and disopyramide may be preferable in patients with vagally mediated AF, whereas beta-blocking agents could possibly be detrimental.•Although there is no clinical evidence, based on the pharmacokinetic profile, tailoring the timing of drug administration to cause maximum drug effect to be nocturnal could be considered.•PVI is the