Novel Parameters to Improve Quantification of Repolarization Reserve and Arrhythmogenesis Using a Dofetilide Challenge

Stams, Trg; Winckels, Stephan K.G.; Oros, Avram; Varkevisser, Rosanne; Oosterhoff, Peter; Nagel, Roel van der; Beekman, Hdm; Vos, Marlies de

doi:10.1016/j.hrthm.2013.09.027

Cited by 6 publications

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“…The arrhythmia score (AS) was calculated as the average of the 3 most severe arrhythmic events during the 10 minutes from the start of dofetilide infusion. 13,14 In order to compare AS during HRP at different frequencies in the inducibility experiment, AS was quantified over the last minute of IVR and the first minute of each pacing frequency.…”

Section: Discussionmentioning

confidence: 99%

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model

et al. 2020

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BACKGROUND The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an I Kr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP.OBJECTIVE The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias.METHODS Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STV ICD ) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STV RV,EGM/LV,MAPD ). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STV ICD threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STV ICD threshold was reached. RESULTSIn experiment 1, 8 of 8 dogs had repetitive TdP, and STV ICD increased from 0.96 6 0.42 ms to 2.10 6 1.26 ms (P ,.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STV RV,EGM/LV,MAPD from 2.02 6 1.12 ms to 0.78 6 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs.CONCLUSION STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias.

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Section: Discussionmentioning

confidence: 99%

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model

et al. 2020

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“…The arrhythmia score (AS) has been developed in an effort to quantify the severity of the arrhythmias. [45] The AS is calculated by averaging the three most severe arrhythmias that occur during 10 minutes from the start of dofetilide infusion. Figures 2A and B show how the individual arrhythmic event is scored: 1 point is given by default for each regular beat in the absence of arrhythmic events.…”

Section: Relation Of Short-term Variability Of Repolarisation To Sevementioning

confidence: 99%

The Increment of Short-term Variability of Repolarisation Determines the Severity of the Imminent Arrhythmic Outcome

Smoczyńska

Beekman

Vos

2019

Arrhythm Electrophysiol Rev

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Ventricular remodelling can make the heart more susceptible to ventricular arrhythmias like torsades de pointes. Understanding the underlying mechanisms of initiation of ventricular arrhythmias and the determining factors for its severity has the potential to uncover new interventions. Beat-to-beat variation of repolarisation, quantified as short-term variability of repolarisation (STV), has been identified as an important factor contributing to arrhythmogenesis. This article provides an overview of experimental data about STV in relation to the initiation of torsades de pointes in a canine model of complete chronic atrioventricular block susceptible to torsades de pointes arrhythmias. Furthermore, it explores STV in relation to the severity of the arrhythmic outcome.

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“…Arrhythmic events were scored to quantify the severity of the arrhythmic outcome [ 24 ]. Single ectopic beats (sEB) were scored with 2 points, multiple ectopic beats (mEB) were scored with 3–5 points and self-terminating TdP arrhythmias were scored with 6–49 points.…”

Section: Methodsmentioning

confidence: 99%

“…The arrhythmic outcome was quantified by the relative TdP score (scored TdP arrhythmias relative to the induction experiment), the total number of shocked TdP arrhythmias, and the total score of all arrhythmic events within the 10 min time window after the start of dofetilide infusion. The arrhythmia score is based on the average of the three highest scored arrhythmic events [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

IKs Activator ML277 Mildly Affects Repolarization and Arrhythmic Outcome in the CAVB Dog Model

et al. 2023

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Long QT syndrome type 1 with affected IKs is associated with a high risk for developing Torsade de Pointes (TdP) arrhythmias and eventually sudden cardiac death. Therefore, it is of high interest to explore drugs that target IKs as antiarrhythmics. We examined the antiarrhythmic effect of IKs channel activator ML277 in the chronic atrioventricular block (CAVB) dog model. TdP arrhythmia sensitivity was tested in anesthetized mongrel dogs (n = 7) with CAVB in series: (1) induction experiment at 4 ± 2 weeks CAVB: TdP arrhythmias were induced with our standardized protocol using dofetilide (0.025 mg/kg), and (2) prevention experiment at 10 ± 2 weeks CAVB: the antiarrhythmic effect of ML277 (0.6–1.0 mg/kg) was tested by infusion for 5 min preceding dofetilide. ML277: (1) temporarily prevented repolarization prolongation induced by dofetilide (QTc: 538 ± 65 ms at induction vs. 393 ± 18 ms at prevention, p < 0.05), (2) delayed the occurrence of the first arrhythmic event upon dofetilide (from 129 ± 28 s to 180 ± 51 s, p < 0.05), and (3) decreased the arrhythmic outcome with a significant reduction in the number of TdP arrhythmias, TdP score, arrhythmia score and total arrhythmic events (from 669 ± 132 to 401 ± 228, p < 0.05). IKs channel activation by ML277 temporarily suppressed QT interval prolongation, delayed the occurrence of the first arrhythmic event and reduced the arrhythmic outcome in the CAVB dog model.

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Novel Parameters to Improve Quantification of Repolarization Reserve and Arrhythmogenesis Using a Dofetilide Challenge

Cited by 6 publications

References 0 publications

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model

The Increment of Short-term Variability of Repolarisation Determines the Severity of the Imminent Arrhythmic Outcome

IKs Activator ML277 Mildly Affects Repolarization and Arrhythmic Outcome in the CAVB Dog Model

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