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Circadian variation of arrhythmic events, electrophysiological properties, and the autonomic nervous system.

Malignant ventricular tachyarrhythmias and sudden cardiac death exhibit a circadian variation with a distinct peak during morning hours. The underlying cause for this observation appears to be complex and multifactorial. For example, in a field study in patients with out-of-hospital cardiac arrest, Arntz and co-workers found a clear diurnal variation in patients with ventricular fibrillation but not in patients with asystole. A better understanding of the triggering factors leading to the initiation of arrhythmias has therefore been a major task in order to find strategies to prevent such catastrophic events. Myocardial ischaemia, as a well known trigger for arrhythmias, has been suggested as a major cause since ischaemia-related conditions such as anginal attacks, myocardial infarction and stroke have been found to occur more frequently during morning hours as well. This may be due to various factors exhibiting a similar diurnal variation, i.e. a morning surge in sympathetic activity and an increase in catecholamine levels, elevated blood pressure, increased platelet aggregability, and diurnal variations in endothelial function. In addition, external factors such as strenuous physical activity and emotional stress have also been found to play a role in the initiation of ventricular arrhythmias. However, despite the fact that all these factors may lead to myocardial ischaemia, the diurnal distribution of malignant arrhythmias is not different in a patient with versus without ischaemic heart disease, suggesting the importance of other factors as well. Previous studies have shown a diurnal variation in electrophysiological properties. For example, the QT interval exhibits a circadian variation, with a longer corrected QT interval during sleep than during waking hours. Furthermore, the dispersion of the corrected QT intervals is greater during daytime than during sleep. These parameters indirectly reflect measures of ventricular action potential duration and repolarization, which are both important determinants for the genesis of arrhythmias. Another parameter more directly reflecting repolarization characteristics is ventricular refractoriness. Ventricular refractoriness has been determined invasively and non-invasively (using the telemetry function of implanted pacemakers) and has been found to be shorter during daytime and longest during sleep. In one study, the time of day was the only independent predictor of ventricular refractory periods, and ventricular refractory periods were shortest around the hour of awakening, i.e. at a time when the incidence of sudden death has been found to be highest. Thus, a circadian variation in electrophysiological properties may play a significant role in the complex pathogenesis of arrhythmia initiation and sudden cardiac death. Beta-blockade eliminates the diurnal variation of ventricular refractory periods, although there is no clear relationship between ventricular refractoriness and plasma catecholamine levels. This suggests that fluctuations in sympathetic nervous activity (which does not directly correlate with plasma norepinephrine concentrations) may be responsible for these observations. In this issue, Simantirakis et al. investigated the relationship between the circadian variation of refractory periods and autonomic nervous system activity. They studied patients with primary conduction disease and without overt heart disease who had been chronically paced after permanent DDD pacemaker implantation. Using the pacemaker programming capabilities they measured both the atrial and ventricular refractory periods at two different cycle lengths bi-hourly over 24 h and correlated these findings with spectral indexes of heart rate variability as a marker of increased sympathetic or parasympathetic tone. The authors could reproduce the previously reported findings of a circadian variation for atrial and ventricular refractory periods, with longer refractory periods during the night (when patients are asleep) and shorter refractory periods during the day. The new finding in the study is that there is a clear relationship between the autonomic tone and the circadian variation of the refractory periods. Atrial and ventricular refractory periods are shorter during periods of high sympathetic tone (indicated by the high power of the low frequency band (LF)), i.e. during daytime, and substantially lengthen during periods of high parasympathetic tone (indicated by Circadian variation of arrhythmic events, electrophysiological properties, and the autonomic nervous system