Epicardial Ablation in Brugada Syndrome

Lambiase, Pier D.; Providência, Rui

doi:10.1016/j.ccep.2020.04.006

“…The hallmark ECG pattern of BrS comprises a coved ST-segment in the right-precordial leads V1 to V3, which may be variably present and can be unmasked or increased after administration of sodium channel blocking drugs (ajmaline, flecainide), or during fever or exercise [36]. BrS patients frequently display low voltages, fractionated late potentials and (subtle) structural abnormalities such as fibrosis in the epicardial layer of the right ventricular outflow tract (RVOT), and arrhythmias are often inducible in the RVOT of affected individuals [37]. Loss of function SCN5A mutations are identified in approximately 20% of BrS patients, while mutations in other ion channel and non-ion channel genes are sporadically found [38,39].…”

Section: Disorders Associated With Nav15 Dysfunctionmentioning

confidence: 99%

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Remme

¹

2023

Phil. Trans. R. Soc. B

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Influx of sodium ions through voltage-gated sodium channels in cardiomyocytes is essential for proper electrical conduction within the heart. Both acquired conditions associated with sodium channel dysfunction (myocardial ischaemia, heart failure) as well as inherited disorders secondary to mutations in the gene SCN5A encoding for the cardiac sodium channel Nav1.5 are associated with life-threatening arrhythmias. Research in the last decade has uncovered the complex nature of Nav1.5 distribution, function, in particular within distinct subcellular subdomains of cardiomyocytes. Nav1.5-based channels furthermore display previously unrecognized non-electrogenic actions and may impact on cardiac structural integrity, leading to cardiomyopathy. Moreover, SCN5A and Nav1.5 are expressed in cell types other than cardiomyocytes as well as various extracardiac tissues, where their functional role in, e.g. epilepsy, gastrointestinal motility, cancer and the innate immune response is increasingly investigated and recognized. This review provides an overview of these novel insights and how they deepen our mechanistic knowledge on SCN5A channelopathies and Nav1.5 (dys)function. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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“…The data obtained strongly indicate that these compounds deserve consideration in the development of pre-clinical approaches for therapeutic protocols of β-thalassemia. These compounds should be considered as repurposed drugs, as quinidine has been employed in a variety of cardiac complications, such as arrythmias, atrial fibrillation, idiopathic ventricular fibrillation, Brugada syndrome, and Short QT syndrome 61 – 63 .…”

Section: Drug Repositioning For Rare Diseases: β-Thalassemiamentioning

confidence: 99%

A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

Prosdocimi¹,

Cosenza²,

Borgatti³

et al. 2022

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Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.

show abstract

“…The data obtained strongly indicate that these compounds deserve consideration in the development of pre-clinical approaches for therapeutic protocols of β-thalassemia. These compounds should be considered as repurposed drugs, as quinidine has been employed in a variety of cardiac complications, such as arrythmias, atrial fibrillation, idiopathic ventricular fibrillation, Brugada syndrome, and Short QT syndrome [61][62][63] .…”

Section: Drug Repositioning For Rare Diseases: β-Thalassemiamentioning

confidence: 99%

A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

Prosdocimi

¹

,

Cosenza

²

,

Borgatti

³

et al. 2022

View full text Add to dashboard Cite

Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.

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Epicardial Ablation in Brugada Syndrome

Cited by 6 publications

References 28 publications

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

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