Abstract
The long QT syndrome (LQTS) is largely treated pharmacologically with β‐blockers, despite the role of sympathetic activity in LQTS being poorly understood. Using the trigger–substrate model of cardiac arrhythmias in this review, we amalgamate current experimental and clinical data from both animal and human studies to explain the mechanism of adrenergic stimulation and blockade on LQT arrhythmic risk and hence assess the efficacy of β‐adrenoceptor blockade in the management of LQTS. In LQTS1 and LQTS2, sympathetic stimulation increases arrhythmic risk by enhancing early afterdepolarizations and transmural dispersion of repolarization. β‐Blockers successfully reduce cardiac events by reducing these triggers and substrates; however, these effects are less marked in LQTS2 compared with LQTS1. In LQTS3, clinical and experimental investigations of the effects of sympathetic stimulation and β‐blocker use have produced contradictory findings, resulting in significant clinical uncertainty. We offer explanations for these contradicting results relating to study sample size, the dose of the β‐blocker administered associated with its off‐target Na+ channel effects, as well as the type of β‐blocker used. We conclude that the antiarrhythmic efficacy of β‐blockers is a genotype‐specific phenomenon, and hence the use of β‐blockers in clinical practice should be genotype dependent.
Our review amalgamates current experimental and clinical data from both animal and human studies to explain the mechanism of adrenergic stimulation and blockade on LQT arrhythmic risk and hence assess the efficacy of β‐adrenoceptor blockade in the management of LQTS.