Discussion

Our patient was an infant with junctional ectopic tachycardia complicated by tachycardia-induced cardiomyopathy. In the current case, heart rate control was successfully achieved by adding ivabradine to the conventional oral antiarrhythmic therapy. Previous reports have shown that ivabradine is effective in both rhythm and heart rate control in junctional ectopic tachycardia.^{Reference Pamukcu and Citli3,Reference Al-Ghamdi, Al-Fayyadh and Hamilton4} In this case, although rhythm control was not achieved, heart rate control alone contributed to sustained improvement in left ventricular function and heart failure.

Non-postoperative junctional ectopic tachycardia, which is associated with heart failure in approximately 15% of cases and has a mortality rate of 4%, is a serious condition in infants.^{Reference Villain, Vetter and Garcia1} A previous study has reported that even if rhythm control is not achieved, treatment can be successful if the heart rate can be reduced to improve haemodynamic stability.^{Reference Sasikumar, Kumar and Balaji5} Thus, as in our patient, if rhythm control cannot be achieved with standard oral antiarrhythmic drugs, the use of ivabradine to achieve heart rate control may be a reasonable therapeutic goal.

In this case, ivabradine might have contributed to heart rate control by suppressing atrioventricular node and ventricular conduction. In junctional ectopic tachycardia, the tachycardia is thought to be driven by abnormal automaticity arising from the atrioventricular node region and the funny current (If) is thought to contribute significantly to its mechanism.^{Reference Dobrzynski, Nikolski and Sambelashvili6} Ivabradine acts on hyperpolarisation-activated cyclic nucleotide-gated (HCN/If) channels in the sinoatrial node, which reduces heart rate.^{Reference Bois, Bescond and Renaudon7} Nevertheless, a recent study has shown that ivabradine can also delay conduction time in the atrioventricular node and ventricles.^{Reference Amstetter, Badt and Rubi8} This is because HCN/If channels are not restricted to the sinoatrial node but are expressed in the atrioventricular node, the cardiac conduction system, and even ventricular cardiomyocytes.^{Reference Depuydt, Peigneur and Tytgat9} Similar cases in which rhythm control was not achieved but successful heart rate control led to clinical improvement have been reported.^{Reference Dieks, Klehs and Müller10}

As rhythm control and heart rate control were challenging to achieve in our patient, sotalol, ivabradine, and propranolol were introduced. Previous studies have shown the application of combination therapies involving ivabradine with amiodarone, propranolol, and flecainide.^{Reference Pamukcu and Citli3,Reference Dieks, Klehs and Müller10,Reference Di Marco, De Nigris, Pepe, Pagano, Di Nardo and Tipo11} Amiodarone and flecainide were ineffective in our patient and therefore were not combined with ivabradine. Nonetheless, there are no clinical reports on the use of ivabradine combined with sotalol.

Sotalol and propranolol may decrease junctional rate through β-blockade. The HCN/If channel is controlled by intracellular cyclic adenosine monophosphate and thus indirectly inhibited by β-blockers.^{Reference DiFrancesco12} Previous reports have shown that sotalol and β-blockers are effective for junctional ectopic tachycardia.^{Reference Kylat and Samson13} In addition, sotalol inhibits the human ether-à-go-go–related gene potassium channel, a mechanism also observed with ivabradine at high concentrations in vivo.^{Reference Melgari, Brack and Zhang14} Thus, in our patient, the combination of ivabradine, sotalol, and propranolol may exert complementary heart rate-controlling effects in junctional ectopic tachycardia by blocking the If channel and human ether-à-go-go–related gene potassium channel.

Before transitioning to oral antiarrhythmic agents, partial heart rate control had been achieved with intravenous landiolol, procainamide, and nifekalant. Landiolol and nifekalant likely contributed to heart rate slowing through β-blockade and IKr inhibition, respectively. Procainamide, as a class Ia agent, decreases automaticity and prolongs refractoriness in atrioventricular nodal tissue^{Reference Wang, Sosa-Suarez and Friedman15}—effects that can slow the heart rate.

The ivabradine dose of 0.4 mg/kg/day used in our case, although higher than that commonly reported for paediatric tachyarrhythmias,^{Reference Pamukcu and Citli3,Reference Dieks, Klehs and Müller10} remains within the established paediatric heart failure dosing range (up to 0.6 mg/kg/day as demonstrated in the previous study) and was safely administered under careful monitoring without adverse events.^{Reference Bonnet, Berger, Jokinen, Kantor and Daubeney16}

Ivabradine is currently used off-label for junctional ectopic tachycardia in Japan; however, internationally, its potential therapeutic role in congenital junctional ectopic tachycardia has been increasingly reported. Several case reports and small series have demonstrated that ivabradine can effectively reduce heart rate and restore sinus rhythm in patients with refractory congenital junctional ectopic tachycardia, either as monotherapy or in combination with other antiarrhythmic drugs. Given its unique mechanism of selective If-channel inhibition without negative inotropic effects,^{Reference Pamukcu and Citli3,Reference Amstetter, Badt and Rubi8,Reference Di Marco, De Nigris, Pepe, Pagano, Di Nardo and Tipo11} ivabradine is now positioned as an important therapeutic option for heart rate control and rhythm stabilisation in difficult-to-treat congenital junctional ectopic tachycardia in the global clinical setting.

Based on this case, ivabradine may reduce heart rate and improve cardiac function and heart failure in junctional ectopic tachycardia cases in which rhythm control is difficult to achieve. Nevertheless, further studies should be conducted to assess the long-term efficacy and safety of this treatment approach.