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.