QT INTERVAL VARIATIONS AND MORTALITY RATE
INTRODUCTION: Extreme prolongation or reduction of the QT interval predisposes patients to malignant ventricular arrhythmias and sudden cardiac death, but dose-response relationships between QT interval and cardiovascular disease mortality is imprecisely known.
METHODS and RESULTS: Prolongation of the QT interval is associated with the occurrence of early after-depolarizations. Early after-depolarizations of sufficient amplitude can generate premature action potentials that lead to cardiac arrhythmias that may progress to ventricular fibrillation and sudden cardiac death. In general, longer QT intervals reflect longer ventricular action potentials, a reduction in repolarizing reserve that is associated with exaggerated spatial and temporal heterogeneity of electrical recovery of the ventricle. This would allow for the development of functional reentry, in which still-activated regions of ventricular myocardium reenter and reactivate regions with shorter action potentials, producing polymorphic ventricular tachycardias. Shortening of the QT interval is associated with exaggerated heterogeneity of repolarization in time and space. The progressive association of QT-interval duration with mortality at the high end of the distribution then would reflect an increased likelihood of ventricular arrhythmias associated with increasing heterogeneity in ventricular action potential duration. The exaggerated heterogeneity of action potential duration creates a substrate for functional reentry similar to that of long QT syndrome but with hastened recovery and reduced refractoriness in the ventricle, and arrhythmias are likely to be even more malignant in short compared with long QT syndromes.
CONCLUSION: Shortened and prolonged QT-interval durations, even within a reference range, are associated with increased mortality risk in the general population.