Discussion
Majority of ATS individuals are caused by heterozygous mutations inKCNJ2 which encodes for the α-subunit of Kir2.1, an inward rectifier potassium channel responsible for late phase of cardiac repolarization. Classic ECG abnormalities include QTc prolongation and prominent U-wave. Various types of VA, including bidirectional VT and PMVT, are prevalent and could be identified in more than 80% of the patients, though sudden cardiac death does not commonly occur2. Current management strategy of ATS is mainly focused on suppression of ventricular ectopy to restore left ventricular function and prevent tachycardia-induced cardiomyopathy3.
These two KCNJ2 [c.557C>G (p.Pro186Arg)]-associated ATS patients who got pregnant and underwent vaginal birth safely without any medications were first reported. Both individuals had VA, micrognathia without periodic paralysis. β-blocker plus Flecainide were shown to be effective when β-blocker alone could not suppress their arrhythmias.
Though the mechanism remains unknown, physiologic changes associated with pregnancy could have significant impact on cardiac conduction in patients with ATS. QTc interval is hormonally regulated and increased estradiol is associated with shorter QTc interval via enhanced membrane trafficking of KCNH2 4. One reported case also showed marked reduction of ventricular ectopy during pregnancy1.
β-blockers are considered mainstay therapy for inherited long QT syndromes, though β-blocker-resistant cases do occur5. Flecainide is a fast-inward sodium channel blocker with pleiotropic effects to reduce the oscillatory potentials. It can also terminate VT by modulating calcium dynamic via inhibiting reverse-mode sodium-calcium exchanger or ryanodine receptor 2 and directly increasing Kir2.1 current with no significant impact on left ventricular function 6. The medication was shown to be effective on reducing VA burden in multiple ATS patients2,3,7–11 (Table 1). The synergistic effect of β-blockers and Flecainide might favor a combination treatment in ATS.
In concordance with previously reported cases, the combination of Flecainide and β-blocker was useful in patients with ATS when β-blocker monotherapy failed to control cardiac arrhythmias.