ArticleHeart rhythm2017
Lidocaine attenuation testing: An in vivo investigation of putative LQT3-associated variants in the SCN5A-encoded sodium channel.
Article in Heart rhythm, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 12 citations in OpenAlex.
- KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences.Clinics (Sao Paulo, Brazil) · 2023Article
- A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood.European journal of medical genetics · 2020Article
- Pilsicainide Administration Unmasks a Phenotype of Brugada Syndrome in a Patient with Overlap Syndrome due to the E1784K SCN5A Mutation.Internal medicine (Tokyo, Japan) · 2020Article
- Gating Properties of Mutant Sodium Channels and Responses to Sodium Current Inhibitors Predict Mexiletine-Sensitive Mutations of Long QT Syndrome 3.Frontiers in pharmacology · 2020Article
- Mexiletine infusion challenge test for neonatal long QT syndrome with 2:1 atrioventricular block.Journal of arrhythmia · 2019Article
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Abstract
backgroundLong QT syndrome type 3 (LQT3) accounts for 5%-10% of long QT syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Approximately 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential.
objectiveThe purpose of this study was to assess the use of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3.
methodsWe reviewed the LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion at 50 μg/(kg⋅min) for 20 minutes. If the corrected QT interval shortened by ≥30 ms, the LAT was defined as positive.
resultsSixteen patients (64%) had a positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT correlated in 86% of cases with abnormal in vitro channel function (mean corrected QT interval attenuation 43 ± 3 ms vs 25 ± 5 ms for wild-type variants; P = .03). Four of 5 patients (80%) with a VUS had a positive LAT (T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated abnormal in vitro function and a positive LAT, opening the door for a potential variant promotion from VUS to likely pathogenic.
conclusionThe LAT may help distinguish true LQT3-causative mutations from an otherwise noncontributory VUS. Given that lidocaine acts as a late sodium current blocker, a positive LAT may enable the early identification of a pathological accentuation of the late sodium current that could be targeted therapeutically.
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