Sodium-channel blockers might contribute to the prevention of ventricular tachycardia in patients with long QT syndrome type 2: a description of 4 cases

Background: β-blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the effect of sodium channel blockers in all LQT patients remains unknown. Methods: We conducted a systematic electronic search of PubMed, Embase and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc≥500 ms and QTc≤460 ms in LQTS patients. Results: Pooled analysis of 14 studies with 213 LQTS patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (MD -49.43, 95%CI -57.80 to -41.05, P<0.001), reduced the incidence of CEs (OR 0.12, 95%CI 0.04 to 0.32, P<0.001) and the proportion of QTc≥500 ms (OR 0.15, 95%CI 0.09 to 0.26, P<0.001), and increased the proportion of QTc≤460 ms (OR 18.00, 95%CI 7.49 to 43.26, P<0.001). Sodium channel blockers significantly shortened QTc both in LQT3 and non-LQT3 patients, while the QTc shortening effect in LQT3 was superior to that in non-LQT3 (57.39 ms vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 ms vs. 49.08 ms vs. 50.10 ms). Conclusions: sodium channel blockers can be useful both in LQT3 and non-LQT3 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.

Download Full-text

Retraction: Sex differences in the expression of sodium/calcium exchanger influence the arrhythmia phenotype in the long QT syndrome type 2

British Journal of Pharmacology ◽

10.1038/bjp.2008.183 ◽

2008 ◽

Cited By ~ 1

Author(s):

G Salama ◽

B London ◽

L J Kerchner ◽

N R Salama ◽

T Liu

Keyword(s):

Sex Differences ◽

Long Qt Syndrome ◽

Syndrome Type ◽

Sodium Calcium Exchanger ◽

Long Qt ◽

Sodium Calcium ◽

Qt Syndrome

Download Full-text

A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

International Journal of Arrhythmia ◽

10.1186/s42444-020-00029-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hyun Sok Yoo ◽

Nancy Medina ◽

María Alejandra von Wulffen ◽

Natalia Ciampi ◽

Analia Paolucci ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Long Qt Syndrome ◽

Cardiac Death ◽

Frameshift Mutation ◽

Alpha Subunit ◽

Syndrome Type ◽

Long Qt ◽

Qt Syndrome ◽

Congenital Long Qt Syndrome

Abstract Background The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. The carriers of the pathogenic variant of KCNH2 gene manifest a phenotype characterized by prolongation of QT interval and increased risk of sudden cardiac death due to life-threatening ventricular tachyarrhythmias. Results A family composed of 17 members with a family history of sudden death and recurrent syncopes was studied. The DNA of proband with clinical manifestations of long QT syndrome was analyzed using a massive DNA sequencer that included the following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 and TRDN. DNA sequencing of proband identified a novel pathogenic variant of KCNH2 gene produced by a heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting in the synthesis of a truncated alpha subunit of the Kv11.1 ion channel. Eight family members manifested the phenotype of long QT syndrome. The study of family segregation using Sanger sequencing revealed the identical variant in several members of the family with a positive phenotype. Conclusions The clinical and genetic findings of this family demonstrate that the novel frameshift mutation causing haploinsufficiency can result in a congenital long QT syndrome with a severe phenotypic manifestation and an elevated risk of sudden cardiac death.

Download Full-text