Congenital long QT syndrome (LQTS) is a cardiac channelopathy, which leads to prolongation of the QT interval. This prolongation can lead to ventricular tachyarrhythmia, syncope and sudden cardiac death (SCD). There are various types of LQTS. Treatment of LQT1 and LQT2 is mainly based on antiadrenergic therapy. LQT3 on the other hand is a result of a mutation of SCN5A gene, which encodes the sodium channels. In this type patients are sensitive to vagal stimuli and episodes tend to occur at rest. Management of LQT3 patients is challenging, beta blockers are thought to be less beneficial and the risk for arrhythmia is higher. Sodium channel blocking compounds which have also pro arrhythmic effect such as ranolazine, mexiletine and flecainide, have been found effective in selective mutations. Prediction of the clinical efficacy based on the phenotype is problematic.
We report a child with congenital LQT3 (V411M) with severe phenotype presenting first with QTC of 620 msec and SCD. Three weeks later she was readmitted with ventricular fibrillation storm and ten appropriate shocks from the implantable cardioverter defibrillator (ICD). In vitro study has shown that the increased open probability of V411M sodium channels during the plateau phase and repolarization due to the activation gain of function in this mutant make them most susceptible to open state block by drugs like flecainide. Treatment with flecainide totally eliminated arrhythmia and the QTC interval shortened significally to 480-500 msec. Three days following cessation of flecainide she received 3 appropriate shocks from the ICD due to recurrence of fatal arrhythmia. Flecainide was immediately resumed. There was no arrhythmia events recorded by ICD during 22 month follow up.
Knowing the specific mutation and understanding of the mechanism at the molecular level has yielded clinically meaningful result. Patient's arrhythmia burden was totally eliminated following successful treatment with flecainide.
