Open AccessGene‐Specific Therapy for Long QT Syndrome
Author(s) -
Rosero Spencer Z.,
Zareba Wojciech,
Robinson Jennifer L.,
Moss Arthur J.
Publication year - 1997
Publication title -
annals of noninvasive electrocardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.494
H-Index - 48
eISSN - 1542-474X
pISSN - 1082-720X
DOI - 10.1111/j.1542-474x.1997.tb00336.x
Subject(s) - medicine , qt interval , lidocaine , sodium channel , sodium channel blocker , long qt syndrome , blockade , herg , repolarization , proarrhythmia , cardiology , adverse effect , pharmacology , anesthesia , sodium , electrophysiology , potassium channel , receptor , chemistry , organic chemistry
Background: One form of the hereditary long QT syndrome (LQT‐3) has recently been shown to be caused by the SCN5A mutation of the human cardiac sodium channel. Cellular studies have suggested that type lb antiarrhythmics may be potentially therapeutic via preferential blockade of the resulting abnormal late inward sodium current. To test this hypothesis, we implemented a pilot study to evaluate the potential for long‐term, gene‐specific therapy in patients with this disease. Methods and Results: The effects of short‐term intravenous lidocaine and oral tocainide were studied in three siblings: two carriers of the SCN5A mutation; and one noncarrier. The two carriers had prolonged QT intervals at baseline, 531 ms, and 566 ms, which markedly shortened with intravenous lidocaine to 438 and 482 ms, respectively. Tocainide‐induced correction of the QT interval was similar in both carriers. The noncarrier did not have any significant change in the QT with either drug. One carrier was then placed on outpatient therapy with oral tocainide, and has demonstrated persistent normalization of the QT interval and T wave morphology during the past 10 months. Conclusion: This is the first demonstration of long‐term outpatient treatment in LQT‐3 using oral tocainide during a 10‐month period. QT shortening was achieved by both intravenous lidocaine and oral tocainide, with no adverse affects. The predominant effect was a reduction in the QT onset interval, suggesting that blockade of the mutant sodium current allows repolarization to begin at an earlier time during the action potential.