Ivabradine use as an antiarrhythmic therapy in congenital junctional ectopic tachycardias

Ergül, Yakup; Öztürk, Erkut

doi:10.1111/pace.13478

Cited by 4 publications

(5 citation statements)

References 6 publications

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“…28 Ivabradine, which works by selective inhibition of hyperpolarization-activated cyclic nucleotide-gated channels, has been shown to be effective. [29][30][31] It has been shown that selective blockade of the rapidly activating delayed rectifier K+channel (I(Kr)) by pure class III antiarrhythmic drugs like nifekalant has been useful in CJET refractory to amiodarone and other drugs. 32 Its mechanism of action is unique in that it does not affect the calcium or sodium channel or the inward rectifier potassium current.…”

Section: Managementmentioning

confidence: 99%

Junctional ectopic tachycardia in infants and children

Kylat

Samson

2019

Journal of Arrhythmia

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Tachyarrhythmias originating in the atrioventricular (AV) node and AV junction including the bundle of His complex (BH) are called junctional tachycardia (JT) or junctional ectopic tachycardia (JET). Congenital JET (CJET) is a rare arrhythmia that occurs in patients without a preceding cardiac surgery and can be refractory to medical therapy and associated with high morbidity and mortality. CJET has a high rate of morbidity and mortality with death occurring in 35% of cases. JET occurring within 72 hours after cardiac surgery is referred to as postoperative JET (POJET) and caused by direct trauma, ischemic, or stretch injury to the AV conduction tissues during surgical repair of congenital heart defects. Focal junctional tachycardia (FJT) is also known as automatic junctional tachycardia and includes paroxysmal or non‐paroxysmal forms. We discuss a staged approach to therapy with improved pharmacological therapies and the use of catheter‐based therapies.

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Section: Managementmentioning

confidence: 99%

Junctional ectopic tachycardia in infants and children

Kylat

Samson

2019

Journal of Arrhythmia

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“…A weak frequency dependence may also serve as an explanation that changes in QRS duration by ivabradine were not rate-dependent ( Amstetter et al, 2021 ). In any case, ivabradine was recently shown to control catecholaminergic polymorphic ventricular tachycardia ( Vaksmann and Klug, 2018 ; Kohli et al, 2020 ) and junctional ectopic tachycardia ( Al-Ghamdi et al, 2013 ; Dieks et al, 2016 ; Kumar et al, 2017 ; Ergul et al, 2018 ; Ergul and Ozturk, 2018 ; Mert et al, 2018 ; Janson et al, 2019 ; Kumar et al, 2019 ). While some of these arrhythmias may be of automatic origin, potentially tied to the function of HCN channels, the antiarrhythmic activity of ivabradine could also stem from the inhibition of VGSCs, in particular under ischemic conditions and in the failing heart, when resting membrane potentials are substantially depolarized ( Bean et al, 1983 ) and channel block would be favored ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent meta-analyses suggested an increased risk of atrial fibrillation associated with ivabradine treatment ( Martin et al, 2014 ; Tanboğa et al, 2016 ; Mengesha et al, 2017 ). On the other hand, ivabradine was able to control ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia ( Vaksmann and Klug, 2018 ; Kohli et al, 2020 ) and junctional ectopic tachycardia ( Al-Ghamdi et al, 2013 ; Dieks et al, 2016 ; Kumar et al, 2017 ; Ergul et al, 2018 ; Ergul and Ozturk, 2018 ; Mert et al, 2018 ; Janson et al, 2019 ; Krishna et al, 2019 ; Kumar et al, 2019 ). Recently, ivabradine has also been considered as a rate control therapy for atrial fibrillation ( Moubarak et al, 2014 ; Kosiuk et al, 2015 ; Turley et al, 2016 ; Wongcharoen et al, 2016 ; Fossati et al, 2017 ), with a current clinical trial to test for this potential new indication ( Fontenla et al, 2019 ), and for other forms of atrial and ventricular tachyarrhythmias [e.g., ( Cohen et al, 2020 ; Kohli et al, 2020 )].…”

Section: Introductionmentioning

confidence: 99%

The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels

et al. 2022

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Background and purpose: Ivabradine is clinically administered to lower the heart rate, proposedly by inhibiting hyperpolarization-activated cyclic nucleotide-gated cation channels in the sinoatrial node. Recent evidence suggests that voltage-gated sodium channels (VGSC) are inhibited within the same concentration range. VGSCs are expressed within the sinoatrial node and throughout the conduction system of the heart. A block of these channels thus likely contributes to the established and newly raised clinical indications of ivabradine. We, therefore, investigated the pharmacological action of ivabradine on VGSCs in sufficient detail in order to gain a better understanding of the pro- and anti-arrhythmic effects associated with the administration of this drug.Experimental Approach: Ivabradine was tested on VGSCs in native cardiomyocytes isolated from mouse ventricles and the His-Purkinje system and on human Nav1.5 in a heterologous expression system. We investigated the mechanism of channel inhibition by determining its voltage-, frequency-, state-, and temperature-dependence, complemented by a molecular drug docking to the recent Nav1.5 cryoEM structure. Automated patch-clamp experiments were used to investigate ivabradine-mediated changes in Nav1.5 inactivation parameters and inhibition of different VGSC isoforms.Key results: Ivabradine inhibited VGSCs in a voltage- and frequency-dependent manner, but did not alter voltage-dependence of activation and fast inactivation, nor recovery from fast inactivation. Cardiac (Nav1.5), neuronal (Nav1.2), and skeletal muscle (Nav1.4) VGSC isoforms were inhibited by ivabradine within the same concentration range, as were sodium currents in native cardiomyocytes isolated from the ventricles and the His-Purkinje system. Molecular drug docking suggested an interaction of ivabradine with the classical local anesthetic binding site.Conclusion and Implications: Ivabradine acts as an atypical inhibitor of VGSCs. Inhibition of VGSCs likely contributes to the heart rate lowering effect of ivabradine, in particular at higher stimulation frequencies and depolarized membrane potentials, and to the observed slowing of intra-cardiac conduction. Inhibition of VGSCs in native cardiomyocytes and across channel isoforms may provide a potential basis for the anti-arrhythmic potential as observed upon administration of ivabradine.

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“… 9 , 10 , 12 For pediatric patients, ivabradine use has been reported in congenital and postoperative junctional ectopic tachycardia, with success. 3 , 4 , 13 Ivabradine has minimal side effects, specifically with regard to hypotension or worsened cardiac function, even in the postoperative population. 4 Bradycardia is the most frequently reported adverse effect, which may limit use; however, many postoperative patients having pacing wires that can be used to mitigate this effect, as was done in our patient.…”

Section: Discussionmentioning

confidence: 99%

“… 1 Recent literature has supported the use of ivabradine in neonatal patients with junctional ectopic tachycardia. 2 , 3 , 4 , 5 , 6 Ectopic atrial tachycardia (EAT) is an automatic tachycardia that can be seen postoperatively in patients after surgery for congenital heart disease (CHD). 7 , 8 These patients have an increased risk of EAT when there is atrial stretch secondary heart failure and/or significant atrioventricular (AV) valve regurgitation.…”

Section: Introductionmentioning

confidence: 99%