Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome
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Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome. / Rivaud, Mathilde R; Bayer, Jason D; Cluitmans, Matthijs; van der Waal, Jeanne; Bear, Laura R; Boukens, Bastiaan J; Belterman, Charly; Gottlieb, Lisa; Vaillant, Fanny; Abell, Emma; Dubois, Remi; Meijborg, Veronique M F; Coronel, Ruben.
I: Heart Rhythm, Bind 18, Nr. 2, 02.2021, s. 278-287.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome
AU - Rivaud, Mathilde R
AU - Bayer, Jason D
AU - Cluitmans, Matthijs
AU - van der Waal, Jeanne
AU - Bear, Laura R
AU - Boukens, Bastiaan J
AU - Belterman, Charly
AU - Gottlieb, Lisa
AU - Vaillant, Fanny
AU - Abell, Emma
AU - Dubois, Remi
AU - Meijborg, Veronique M F
AU - Coronel, Ruben
N1 - Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Action Potentials/physiology
KW - Animals
KW - Disease Models, Animal
KW - Electrocardiography
KW - Heart Conduction System/physiopathology
KW - Heart Rate/physiology
KW - Long QT Syndrome/etiology
KW - Swine
KW - Torsades de Pointes/complications
U2 - 10.1016/j.hrthm.2020.09.020
DO - 10.1016/j.hrthm.2020.09.020
M3 - Journal article
C2 - 33031961
VL - 18
SP - 278
EP - 287
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 2
ER -
ID: 396850897