New echocardiographic insights in short QT syndrome: More than a channelopathy?

Frea, Simone; Giustetto, Carla; Capriolo, Michele; Scrocco, Chiara; Fornengo, Cristina; Benedetto, Sara; Bianchi, Francesca; Pidello, Stefano; Morello, Mara; Gaïta, Fiorenzo

doi:10.1016/j.hrthm.2015.05.024

Cited by 40 publications

(25 citation statements)

References 29 publications

(33 reference statements)

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“…Evidence of electrical and structural remodelling in SQT3 patients is currently lacking; nevertheless, these factors may contribute to the arrhythmia substrate [23,52] and give rise to multiple wavelets characteristic of AF. A further limitation may come from the fact that cardiac mechanical contraction was not considered, which, for ventricular function at least, has previously been suggested to be affected in SQTS patients [53–55], and may affect re-entrant wave dynamics [56,57]. …”

Section: Discussionmentioning

confidence: 99%

Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria

Whittaker

Harchi

et al. 2017

PLoS Comput Biol

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Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF.

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Section: Discussionmentioning

confidence: 99%

Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria

Whittaker

Harchi

et al. 2017

PLoS Comput Biol

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“…Short QTc duration has not been shown to have a significant prognostic effect in low‐risk patients, even under the more strict definition of the Seattle criteria or in a large paediatric, adolescent or young adult cohort . It is, however, associated with impaired myocardial contraction, which prompts the question whether similar effects are induced by the metabolic derangements seen in severe sepsis.…”

Section: Discussionmentioning

confidence: 99%

Corrected QT interval anomalies are associated with worse prognosis among patients suffering from sepsis

Wasserstrum

Lotan

Itelman

et al. 2016

Internal Medicine Journal

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“…In our opinion it is an early marker of the electromechanical dispersion that increases the susceptibility to ventricular arrhythmias in the presence of structural cardiomyopathy and channellopaties. 29 We would like to underline that both patients with ICD devices implanted for secondary prevention reported a high ventricular extrasystole burden at the device interrogation during the follow-up. From this point of view we would like to speculate about the trigger of such arrhythmic events.…”

Section: Discussionmentioning

confidence: 96%