Shortening of the Short Refractory Periods in Short QT Syndrome

Rollin, Anne; Gandjbakhch, Estelle; Giustetto, Carla; Scrocco, Chiara; Fourcade, C; Monteil, Benjamin; Mondoly, Pierre; Cardin, Christelle; Maupain, Carole; Gaïta, Fiorenzo

doi:10.1161/jaha.117.005684

Cited by 8 publications

(3 citation statements)

References 29 publications

(84 reference statements)

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“…[59]. A longer ventricular refractory period may be beneficial since the opposite has been associated with an increased risk of ventricular extrasystolia [60]. In 2007, Fox and colleagues calculated that a 10-bpm reduction in HR produces a 30% reduction in the relative risk of cardiac death after a heart infarction [61].…”

Section: Discussionmentioning

confidence: 99%

Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study

et al. 2022

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Dexmedetomidine (DEX) is a commonly used sedative agent with no or minimal effects on breathing. DEX may also be beneficial in myocardial protection. Since the mechanisms of cardiac effects are not well known, we carried out a descriptive review and examined the effects of DEX on myocardial electrical conduction in a prospective and controlled manner. For the review, clinical studies exploring DEX in myocardial protection published between 2020-2022 were explored. A case study included 11 consecutive patients at a median (range) age of 48 (38–59), scheduled for elective radiofrequency ablation of paroxysmal atrial fibrillation. A bolus dose of DEX 1 µg/kg given in 15 min was followed by a continuous infusion of 0.2–0.7 µg/kg/h. Direct intracardiac electrophysiologic measurements, hemodynamics and oxygenation were measured before and after the DEX bolus. Experimental studies show that DEX protects the heart both via stabilizing cardiac electrophysiology and reducing apoptosis and autophagy after cell injury. The clinical evidence shows that DEX provides cardiac protection during different surgeries. In a clinical study, DEX increased the corrected sinus node recovery time, prolongated the atrioventricular (AV) nodal refractory period and cycle length producing AV nodal Wenckebach retrograde conduction block. DEX has a putative role in organ protection against hypoxic, oxidative and reperfusion injury. DEX slows down the firing of the sinus node and prolongs AV refractoriness.

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Section: Discussionmentioning

confidence: 99%

Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study

et al. 2022

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“…Interestingly, PQ segment depression has been reported in 52 of a cohort of 64 (>80 %) SQTS patients and may potentially constitute an additional marker for the syndrome [26], though further work is required to investigate this. Recently, a refractory period cut-off of 200 ms in the right ventricular outflow tract during invasive testing and pacing at basic cycle length of 500 600 ms has been proposed as a means of identifying true SQTS from individuals without the syndrome who possess borderline QT intervals [27].…”

Section: W Qtmentioning

confidence: 99%

Emerging therapeutic targets in the short QT syndrome

Hancox

Whittaker

Du³

et al. 2018

Expert Opinion on Therapeutic Targets

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Short QT Syndrome (SQTS) is a rare but dangerous condition characterised by abbreviated repolarisation, atrial and ventricular arrhythmias and risk of sudden death. Implantable cardioverter defibrillators (ICDs) are a first line protection against sudden death, but adjunct pharmacology is beneficial and desirable. Areas covered: The genetic basis for genotyped SQTS variants (SQT1-SQT8) and evidence for arrhythmia substrates from experimental and simulation studies are discussed. The main ion channel/transporter targets for antiarrhythmic pharmacology are considered in respect of potential genotype-specific and non-specific treatments for the syndrome. Expert opinion: Potassium channel blockade is valuable for restoring repolarisation and QT interval, though genotype-specific limitations exist in the use of some K channel inhibitors. A combination of K current inhibition during the action potential plateau, with sodium channel inhibition that collectively result in delaying repolarisation and post-repolarisation refractoriness is likely to be valuable in prolonging effective refractory period and wavelength for re-entry. Genotype-specific K channel inhibition is limited by a lack of targeted inhibitors in clinical use, though experimentally available selective inhibitors now exist. The relatively low proportion of successfully genotyped cases justifies an exome or genome sequencing approach, to reveal new mediators and targets, as demonstrated recently for SLC4A3 in SQT8.

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“…Modified from [13] with additional information from [14], [18] and [85]. ♂ -inherited from father; ♀ inherited from mother; * truncation mutant the ECG (seen in > 80% of 64 patients studied [28] and in a further recent case report [29]) a refractory period cut-off of 200 ms in the right ventricular outflow tract during invasive testing (whilst pacing at a cycle length of 500-600 ms) [30]. Third, the atrial tachyarrhythmia in SQTS patients presenting with AF can make it difficult to measure the QT interval accurately and some SQTS cases could be missed in such a scenario.…”

Section: Complexities In the Diagnosis Of The Sqtsmentioning

confidence: 99%

Learning from studying very rare cardiac conditions: the example of short QT syndrome

Hancox

Whittaker

Zhang

et al. 2019

J Congenit Heart Dis

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Background: Some congenital heart conditions are very rare. In a climate of limited resources, a viewpoint could be advanced that identifying diagnostic criteria for such conditions and, through empiricism, effective treatments should suffice and that extensive mechanistic research is unnecessary. Taking the rare but dangerous short QT syndrome (SQTS) as an example, this article makes the case for the imperative to study such rare conditions, highlighting that this yields substantial and sometimes unanticipated benefits. Genetic forms of SQTS are rare, but the condition may be under-diagnosed and carries a risk of sudden death. Genotyping of SQTS patients has led to identification of clear ion channel/transporter culprits in < 30% of cases, highlighting a role for as yet unidentified modulators of repolarization. For example, recent exome sequencing in SQTS has identified SLC4A3 as a novel modifier of ventricular repolarization. The need to distinguish "healthy" from "unhealthy" short QT intervals has led to a search for additional markers of arrhythmia risk. Some overlap may exist between SQTS, Brugada Syndrome, early repolarization and sinus bradycardia. Genotype-phenotype studies have led to identification of arrhythmia substrates and both realistic and theoretical pharmacological approaches for particular forms of SQTS. In turn this has increased understanding of underlying cardiac ion channels. In silico and pharmacological data have highlighted risks with abbreviation of refractoriness accompanied by local dispersion of repolarization, and this urges caution with the deployment of K + channel activation as a novel antiarrhythmic approach. The association between abbreviated QT c intervals and primary carnitine deficiency, particularly in patients with concomitant cardiomyopathy illustrates a link between metabolism and electrogenesis, in which the correct identification of causation could, in some cases, lead to dietary intervention that may obviate the need for antiarrhythmic or heart failure drugs. Conclusions: As illustrated here for the SQTS, the detailed study of rare disorders is both directly beneficial for the treatment/management of affected patients and for increasing the understanding of associated underlying cardiac physiology and pharmacology. The pursuit of underlying gene mutations can lead to unanticipated new links between particular genes and cardiac electrophysiology, opening new avenues for research and potential therapeutic intervention.

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Shortening of the Short Refractory Periods in Short QT Syndrome

Cited by 8 publications

References 29 publications

Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study

Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study

Emerging therapeutic targets in the short QT syndrome

Learning from studying very rare cardiac conditions: the example of short QT syndrome

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