Genetics of acquired long QT syndrome
Dan M. Roden, Prakash C. Viswanathan
Dan M. Roden, Prakash C. Viswanathan
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2025-2032. https://doi.org/10.1172/JCI25539.
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Review Series

Genetics of acquired long QT syndrome

Abstract

The QT interval is the electrocardiographic manifestation of ventricular repolarization, is variable under physiologic conditions, and is measurably prolonged by many drugs. Rarely, however, individuals with normal base-line intervals may display exaggerated QT interval prolongation, and the potentially fatal polymorphic ventricular tachycardia torsade de pointes, with drugs or other environmental stressors such as heart block or heart failure. This review summarizes the molecular and cellular mechanisms underlying this acquired or drug-induced form of long QT syndrome, describes approaches to the analysis of a role for DNA variants in the mediation of individual susceptibility, and proposes that these concepts may be generalizable to common acquired arrhythmias.

Authors

Dan M. Roden, Prakash C. Viswanathan

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Figure 4

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Luo-Rudy simulations showing the concept of repolarization reserve. The ...
Luo-Rudy simulations showing the concept of repolarization reserve. The blue line shows the effect of reducing IKs by 15%, as might be expected in a subtle congenital long QT syndrome mutation. The green line shows the expected prolongation of the control action potential resulting from 75% IKr blockade. The red line shows the effect of the same degree of drug blockade applied to the simulation with 15% IKs blockade. Not only is there marked exaggeration of action potential prolongation, but an EAD with a triggered upstroke is also generated; L-type calcium current generates the upstroke in this model.