Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: Implications for gene-specific therapy

Peter J. Schwartz, Silvia G. Priori, Emanuela H. Locati, Carlo Napolitano, Francesco Cantù, Jeffrey A. Towbin, Mark T. Keating, Hicham Hammoude, Arthur M. Brown, Ling Sing K Chen, Thomas J. Colatsky

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene. These findings opened the possibility of attempting gene-specific control of ventricular repolarization. We tested the hypothesis that the QT interval would shorten more in LQT3 than in LQT2 patients in response to mexiletine and also in response to increases in heart rate. Methods and Results: Fifteen LQTS patients were studied. Six LQT3 and 7 LQT2 patients were treated with mexiletine, and its effects on QT and QTc were measured. Mexiletine significantly shortened the QT interval among LQT3 patients (QTc from 535±32 to 445±31 ms, Pc from 530±79 to 503±60 ms, P=NS). LQT3 patients (n=7) shortened their QT interval in response to increases in heart rate much more than LQT2 patients (n=4) and also more than 18 healthy control subjects (9.45±3.3 versus 3.95±1.97 and 2.83±1.33, P+ channel blockers and from cardiac pacing because they would be at higher risk of arrhythmia at slow heart rates. Conversely, LQT2 patients may be at higher risk to develop syncope under stressful conditions because of the combined arrhythmogenic effect of catecholamines with the insufficient adaptation of their QT interval when heart rate increases.

Original languageEnglish
Pages (from-to)3381-3386
Number of pages6
JournalCirculation
Volume92
Issue number12
Publication statusPublished - Dec 15 1995

Keywords

  • Death, sudden
  • Genes
  • Long QT syndrome
  • Mexiletine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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