The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children

Chockalingam, Priya; Clur, Sally‐Ann B.; Breur, Johannes M.P.J.; Kriebel, Thomas; Paul, Thomas; Rammeloo, Lukas A. J.; Wilde, Arthur A.M.; Blom, Nico A.

doi:10.1016/j.hrthm.2012.08.011

Cited by 41 publications

(33 citation statements)

References 19 publications

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“…Mutations in SCN5A have been identified in families with hereditary PCCD through linkage analysis (1,22). Similar to PCCD patients and children with lossof-function SCN5A mutations (1,8), SCN5A E558X/+ pigs exhibited conduction slowing at an early age that progressively worsened with maturity, as evidenced by an age-dependent sensitivity to flecainide. Lenegre as well as Lev described sclerotic changes in the cardiac conduction system of PCCD patients (23); however, this was not observed in sexually mature SCN5A E558X/+ pigs, despite ECG evidence of slowed conduction.…”

Section: Discussionmentioning

confidence: 99%

“…Functional assessments of the sinoatrial and AV nodes demonstrated significantly prolonged corrected sinus node recovery time and AV Wenckebach cycle length, respectively, in SCN5A E558X/+ animals ( Figure 2D). Therefore, SCN5A E558X/+ pigs accurately phenocopy conduction disease, including abnormalities of the specialized conduction system, seen in patients with loss-of-function sodium channel mutations (1,8,13,14). jci.org…”

Section: In Vivo Electrophysiological Analysis Of Scn5amentioning

confidence: 99%

“…BrS is associated with sudden death due to polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and is diagnosed by the ECG pattern of coved-type ST elevation with terminal T-wave inversions in leads V1-V3, which can be stable or transient (6). Mutations in SCN5A have been identified in 20%-30% of BrS patients, and mutant carriers typically manifest some level of conduction disease (1,7,8).…”

Section: Introductionmentioning

confidence: 99%

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Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: In Vivo Electrophysiological Analysis Of Scn5amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias

et al. 2014

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“…Arrhythmias in such children can be precipitated by fever and vaccination. β-blockers may have a preventive role in mild cases and ICD in severe cases (Chockalingam et al 2012). Recently, a novel mutation in Laminin, LMNA (c.871G>A, p.E291K) associated with familial dilated cardiomyopathy and SCD has been reported (Alexandra et al 2015).…”

Section: Channelopathiesmentioning

confidence: 99%

Role of risk stratification and genetics in sudden cardiac death

Rai

Agrawal

2017

Can. J. Physiol. Pharmacol.

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Keyword:Sudden cardiac death, coronary artery disease, heart failure, Arrhythmias, Atrial fibrillation https://mc06.manuscriptcentral.com/cjpp-pubs AbstractSudden cardiac death (SCD) is a major public health issue due to its increasing incidence in the general population and the difficulty in identifying high-risk individuals.Nearly 300,000-350,000 patients in the United States and 4-to 5 million patients in the world die from SCD. Coronary artery disease and advanced heart failure are the main etiology for SCD. Ischemia of any cause precipitates lethal arrhythmias, and ventricular tachycardia and ventricular fibrillation are the most common lethal arrhythmias precipitating SCD. Pulse-less electrical activity, brady-arrhythmia and electromechanical dissociation also result in SCD.Most sudden cardiac deaths occur out-of-the-hospital setting, so it is difficult to estimate the public burden, which results in overestimating the incidence of SCD. The insufficiency and limited predictive value of various indicators and criteria for SCD result in the increasing incidences. As a result, there is a need to develop better risk stratification criteria and find modifiable variables to decrease the incidence. Primary and secondary prevention and treatment of SCD need further research. This critical review is focused on the etiology, risk factors, prognostic factors and importance of risk stratification of SCD.Key words: Sudden cardiac death, Coronary artery disease, Heart failure, Arrhythmias, Atrial fibrillation, Ventricular fibrillation, Channelopathies, Risk stratification, Prevention

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“…Agerelated fibrosis has indeed been shown in a haploinsufficient Scn5a mouse model (Scn5a +/-mice), with resultant progressive impairment of atrial and ventricular conduction (18). It is not known whether the individuals in published pediatric cases that are described as merely having conduction disease (14) will go on to develop a BrS-type ECG later in life. Similarly, it remains to be seen whether the mutant Yucatan pigs developed by Park et al will develop a BrS pattern when they mature.…”

Section: Bringing Home the Baconmentioning

confidence: 99%