Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome

Mathilde R Rivaud*, Jason D Bayer, Matthijs Cluitmans, Jeanne van der Waal, Laura R Bear, Bastiaan J Boukens, Charly Belterman, Lisa Gottlieb, Fanny Vaillant, Emma Abell, Remi Dubois, Veronique M F Meijborg, Ruben Coronel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization.

OBJECTIVE The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance.

METHODS Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart.

RESULTS pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations.

CONCLUSION pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalHeart Rhythm
Volume18
Issue number2
Early online date5 Oct 2020
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Long QT syndrome
  • Torsades de pointes arrhythmia
  • Repolarization
  • Reentry
  • Restitution

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