Use of a subcutaneous <scp>ICD</scp> in a patient with short <scp>QT</scp> syndrome

Mondoly, Pierre; Cardin, Christelle; Rollin, Anne; Duparc, Alexandre

doi:10.1002/ccr3.432

Cited by 8 publications

(4 citation statements)

References 4 publications

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“…Although the use of ICD may be considered, inappropriate shocks may occur due to the double-counting phenomenon (QRS complexes and T-waves). 190 , 191 …”

Section: Channelopathiesmentioning

confidence: 99%

The Brazilian Society of Cardiology and Brazilian Society of Exercise and Sports Medicine Updated Guidelines for Sports and Exercise Cardiology - 2019

Ghorayeb¹,

Stein²,

Daher³

et al. 2019

Arquivos Brasileiros De Cardiologia

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“…Although the use of ICD may be considered, inappropriate shocks may occur due to the double-counting phenomenon (QRS complexes and T-waves). 190 , 191 …”

Section: Channelopathiesmentioning

confidence: 99%

The Brazilian Society of Cardiology and Brazilian Society of Exercise and Sports Medicine Updated Guidelines for Sports and Exercise Cardiology - 2019

Ghorayeb¹,

Stein²,

Daher³

et al. 2019

Arquivos Brasileiros De Cardiologia

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“…Moreover, the QT interval does not fall within the normal range over time by using the ICD. SQTS patients may benefit from subcutaneous ICD therapy, but additional clinical cases are needed to affirm the efficacy and safety of such device [ 14 ]. Although the ICD remains the mainstay of treatment for SQTS patients, pharmacological therapy may be useful as an adjunct to the ICD therapy or may restore the normal QT interval and suppress atrial and ventricular fibrillation.…”

Section: Introductionmentioning

confidence: 99%

In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles

2017

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AimsShort QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology.MethodsThe ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate IKr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the IKr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC50) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue.ResultsAt the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD90), whereas quinidine caused a significant prolongation of APD90. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide.ConclusionsThe simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients.

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“…As the QT interval is not restored within the normal range over time, ICD is unsuitable for SQTS patients [ 12 ]. Although SQTS patients may benefit from subcutaneous ICD, additional cautions are needed to affirm the safety of such device [ 15 ]. To effectively treat SQTS patients, pharmacological therapy may be the primary modality to restore the normal QT interval and protect against arrhythmia [ 9 , 11 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of amiodarone on short QT syndrome variant 3 in human ventricles: a simulation study

2017

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BackgroundShort QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS. Therefore, in this study, we used computational modeling to assess the effects of amiodarone, class III anti-arrhythmic agent, on human ventricular electrophysiology in SQT3.MethodsThe ten Tusscher et al. model for the human ventricular action potentials (APs) was modified to incorporate I K1 formulations based on experimental data of Kir2.1 channels (including WT, WT-D172N and D172N conditions). The modified cell model was then implemented to construct one-dimensional (1D) and 2D tissue models. The blocking effects of amiodarone on ionic currents were modeled using IC50 and Hill coefficient values from literatures. Effects of amiodarone on APD, ERP and pseudo-ECG traces were computed. Effects of the drug on the temporal and spatial vulnerability of ventricular tissue to genesis and maintenance of re-entry were measured, as well as on the dynamic behavior of re-entry.ResultsAmiodarone prolonged the ventricular cell APD and decreased the maximal voltage heterogeneity (δV) among three difference cells types across transmural ventricular wall, leading to a decreased transmural heterogeneity of APD along a 1D model of ventricular transmural strand. Amiodarone increased cellular ERP, prolonged QT interval and decreased the T-wave amplitude. It reduced tissue’s temporal susceptibility to the initiation of re-entry and increased the minimum substrate size necessary to sustain re-entry in the 2D tissue.ConclusionsAt the therapeutic-relevant concentration of amiodarone, the APD and ERP at the single cell level were increased significantly. The QT interval in pseudo-ECG was prolonged and the re-entry in tissue was prevented. This study provides further evidence that amiodarone may be a potential pharmacological agent for preventing arrhythmogenesis for SQT3 patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12938-017-0369-0) contains supplementary material, which is available to authorized users.

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Use of a subcutaneous ICD in a patient with short QT syndrome

Cited by 8 publications

References 4 publications

The Brazilian Society of Cardiology and Brazilian Society of Exercise and Sports Medicine Updated Guidelines for Sports and Exercise Cardiology - 2019

The Brazilian Society of Cardiology and Brazilian Society of Exercise and Sports Medicine Updated Guidelines for Sports and Exercise Cardiology - 2019

In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles

Effects of amiodarone on short QT syndrome variant 3 in human ventricles: a simulation study

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