Abstract Background/Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia affecting 2% of the population. Within the broad spectrum of AF symptomatology, there is a particular subset of patients that show a predominant or even exclusive nocturnal onset of paroxysmal AF. Purpose The aim of this study is to assess the timing of onset of AF in the 24-hour cycle and to assess whether a circadian rhythm is present in the onset of AF. Methods The MEDLINE, EMBASE, and CENTRAL databases, searched from inception to September 2023, provided 18 studies detailing the onset of AF in a 24-hour cycle. Patients had either paroxysmal or persistent AF. Studies performed in ICU populations (n=3) were omitted due to different triggers for AF. Time of AF onset was determined either by Cardiac Implantable Electronic Device (CIED) (n=5), Holter (n=7) or minute history taking (n=3). The presence and statistical significance of a 24-hour periodicity is tested using the cosinor analysis: Y(t)= A ⋅ sin(2πft + α) + β where the amplitude, frequency, phase and error (A, f, α and β, respectively) are computed by single harmonic regression using a nonlinear least-squares method. Goodness of fit is estimated using R2, the statistical significance of the model is tested using a zero-amplitude test. Results The 15 studies included 2.080 patients with 11.886 onsets of AF. The blue bars in Figure 1 represent the total of AF onsets from all studies per hour. The pattern of onset AF can be approximated well by a single sine function (Onset(t)= 95.7915 ⋅ sin((2π ⋅ 0.0417 ⋅ t) – 1.8386) + 510.5500, R2 0.77, P = 0.03) with a 24-hour period, clearly establishing the 24-hour rhythmicity in the onset of AF (Figure 1, red line). Hours with significantly more onset of AF compared to the mean, assessed by residual Chi2 testing, are exclusively nocturnal (22.00-7.00, indicated by a moon symbol in Figure 1) while hours with significantly less onset are exclusively during daytime (7.00-22.00, indicated by a sun symbol in Figure 1). Conclusion Despite the potential limitations due to the methods used, such as arrhythmia discrimination in CIED-studies and asymptomatic episodes in case of history taking, the overall picture of predominance of nocturnal AF onset is clearly established. Multiple pathophysiological mechanisms might underlie this circadian pattern and nocturnal predominance, like obstructive sleep apnea and increased vagal tone, which should be subject of further research.time of onset of AF over a 24h period

The circadian pattern of atrial fibrillation onset