Insights Into the Pathogenesis of Sudden Cardiac Death From Analysis of Circadian Fluctuations of Potential Triggering Factors

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Abstract
Sudden cardiac death continues to be a poorly understood event in terms of its underlying pathophysiological mechanisms. The observation of a circadian variability in the incidence of this catastrophic event with a prominent peak in the early morning hours provides an opportunity to study triggering factors that may play a causative role in the genesis of sudden cardiac death. As reviewed in this article, there is convincing evidence that transient disturbances in autonomic tone and the resulting consequences may predispose the heart to increased electrical vulnerability. This evidence is based for instance on circadian fluctuations of spontaneous ventricular ectopic activity and transient ischemia, which may serve as trigger factors for the genesis of sustained ventricular tachyarrhythmias. Analysis of heart rate variability provides further evidence of reduced vagal and elevated sympathetic tone during the morning hours particularly in patients with compromised left ventricular function. Diurnal variations in ventricular repolarization as indicated by QT interval changes in the surface ECG also support the concept of triggering factors in the genesis of sudden cardiac death. Therapeutic measures aiming at a reduction in sympathetic input to the heart have been successful in preventing ventricular fibrillation and thus indicate the importance of unbalanced sympathetic tone in patients prone to sudden cardiac death.