Sympathetic nervous system overactivity has been linked to ventricular tachyarrhythmias and sudden death. It has been hypothesized that the extent and nature of the arrhythmogenic effect of sympathetic stimulation depends on the underlying myocardial substrate, the mechanism of the arrhythmia, and the integrated effects of sympathetic stimulation in the particular individual circumstance. Multiple direct and indirect mechanisms of adrenergic action on the heart may benefit from the known antiarrhythmic actions of β-blocker therapy and other interventions that decrease sympathetic tone. The antiarrhythmic mechanism of β-blockade (and possibly α-blockade) will depend on the specific mechanism of the individual arrhythmia and will differ for those arrhythmias caused by tachycardia and ischemia, those caused by reentry and promoted by decreased conduction velocity and shortened refractoriness, and those caused by early or delayed afterdepolarizations, usually in the context of prolonged action potential duration. Antagonism of cardiac adrenergic activity by β-blockade in particular is the best-established drug therapy to prevent ventricular arrhythmias.
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