Mechanisms of torsades de pointes

Jules C. Hancox, Michael J. Curtis

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


This chapter considers mechanisms of torsades de pointes (TdP) linked to delayed ventricular repolarization. Major ionic conductances contributing to action potential repolarization are summarized. The key role of IKr as an anti-target in drug-induced long QT syndrome (diLQTS) is considered, as is more recent evidence implicating late Na current (INa,L) enhancement as an additional mechanism by which chronic drug exposure can prolong ventricular action potentials. Factors influencing repolarization reserve, heterogeneity (dispersion) of repolarization and formation of early afterdepolarizations (EADs) are described. Evidence for TdP triggers and maintenance mechanisms from models of congenital LQTS variants 1–3 is discussed. Models of and issues pertaining to evaluation of TdP in diLQTS are then considered, including the use of surrogate measures as exemplified by the TRiAD model. Across the different forms of LQTS considered, EADs are strongly implicated as trigger events for TdP, whilst dispersion of repolarization is a likely maintenance substrate.

Original languageEnglish
Title of host publicationTorsades de Pointes
Number of pages27
ISBN (Electronic)9780128214466
ISBN (Print)9780128214619
Publication statusPublished - 1 Jan 2022


  • Dispersion of repolarization
  • EAD
  • Early afterdepolarization
  • hERG
  • I
  • LQTS
  • QT interval
  • Reentry
  • Repolarization reserve
  • Torsades de pointes


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