Introduction
Ivabradine alters the ion flow in hyperpolarization-activated cyclic nucleotide-gated channels (F channels), which cause spontaneous depolarisation in cardiac pacemaker cells, prolonging diastolic depolarisation and lowering heart rate. Reference Nawarskas, Bowman and Anderson1 It is used to treat congenital/surgical junctional ectopic tachycardia, inappropriate sinus tachycardia, and cardiomyopathy in children. Reference Ergul, Ozturk, Ozgur, Ozyurt, Cilsal and Guzeltas2–Reference Arvind, Kothari and Juneja8 In recent years, case and case series reports have been published about using of automaticity-related resistant focal atrial tachycardia. Here, we report the case of an infant who had multidrug-resistant supraventricular tachycardia, which may have been caused by the accessory pathway. The baby didn’t respond to conventional medication therapy and was able to achieve sinus rhythm by administering ivabradine.
Case
Due to a history of foetal arrhythmia, a 38-day-old male patient was brought in for a check-up at the paediatric cardiology outpatient clinic. From his history, after normal vaginal birth at the 38th week, he was taken to ICU due to a history of prenatal arrhythmia and he was released from the newborn critical care unit and placed under outpatient monitoring as no tachyarrhythmia was found during the postnatal 5-day follow-up. During this time, 24-hour rhythm Holter monitoring revealed rare supraventricular extrasystoles. His family history did not include any history of arrhythmia or cardiac disease. Based on his prenatal medical history, the mother had been hospitalised for a day because of episodes of foetal nonsustained tachycardia. Foetal bradycardia because of nonconducted atrial extrasystoles was observed during the follow-up, and the frequency of nonsustained tachycardia had decreased. Nevertheless, it was discovered during the follow-up that the mother’s medication was not started because foetal cardiac functions were normal and foetus did not exhibit persistent tachycardia.
The patient was tachycardic on physical examination and had a heart rate of 240 beats/min on postnatal day 38. On the electrocardiogram, a heart rate of 246 beats per minute was responsible for the short RP but narrow QRS tachycardia with an RP > 70 ms. Three intravenous adenosine doses (0.1, 0.2, and 0.3 mg/kg) were administered to the patient upon admission to the emergency room (see Figure 1). With intravenous adenosine treatment, the tachycardia stopped for a short time, but it started again (Figure 2). The short-term cessation of tachycardia with adenosine often indicates an atrioventricular node-involving tachycardia, and considering the patient’s age, re-entry was primarily suspected. The fact that the tachycardia ends with a p wave. Amiodarone loading was performed (5mg/kg) and the maintenance infusion (10 mg/kg) was continued. The patient’s heart rate was observed to be between 240 and 250 beats per minute. After amiodarone loading, the tachycardia persisted, thus esmolol infusion was initiated (100mcg/kg/min), and the patient was admitted to the ICU. Since tachycardia continued, the esmolol dose was increased. Echocardiography revealed mild mitral regurgitation. The ejection fraction was found to be 65%. With esmolol infusion (150 mc/kg/min), the rate of tachycardia decreased, although sinus rhythm was not discernible. Amiodarone loading was infused a second time at a dose of 5 mg/kg. On the first day of the follow-up, the heart rate was 200 beats per minute, but tachycardia still persisted. On the second day, since the tachycardia persisted, flecainide 80 mg/m2/g was started. Propranolol (3 mg/kg/g) was continued as an oral beta blocker. In the follow-up, the patient’s heart rate was approximately 180 beats per minute, and the tachycardia pattern persisted with wide QRS. The dosage of flecainide was decreased (50mg/m2/g). Sinus rhythm could not be established. Recurrent episodes of tachycardia were observed, with spontaneous termination occurring at frequent intervals, as evidenced by the presence of p waves at the points of termination on the electrocardiogram (Figure 3).
Electrocardiography of the patient upon admission with narrow QRS tachycardia at a rate of 260 beats/min.
In the electrocardiogram taken during adenosine treatment, tachycardia ends for a short time and then starts again.
Recurrent episodes of tachycardia with spontaneous termination occurring at frequent intervals, p waves at the points of termination supraventricular tachycardia on the electrocardiogram.
On the fourth follow-up day, the tachycardia persisted. Heart rate and blood pressure were both within normal limits during the follow-up. Ivabradine was started at 0.05 mg/kg/dose in two doses due to persistent supraventricular tachycardia that was resistant to multiple antiarrhythmic therapies. Approximately 4 hours after the first dose of ivabradine, heart rate decreased from 180 to 110 beats/min and sinus rhythm was achieved. The next day, ivabradine dosage was raised (0.1mg/kg/dose) because short-term supraventricular tachycardia attacks persisted, and this prevented further supraventricular tachycardia attacks. Flecainid was stopped and amiodarone was taken at a lower dosage. Two days after being brought to hospital for sinus rhythm, he was brought to the outpatient clinic. Supraventricular tachycardia was not seen in the outpatient clinic controls on electrocardiogram and rhythm Holter. Amiodarone was tapered down and then stopped. Additionally, the beta blocker dosage was decreased and stopped, and no tachycardia recurrence was noted during the 7-month follow-up with only ivabradine treatment.
Discussion
In our case, treatment with ivabradine was successful in a patient with resistant supraventricular tachycardia who had a short RP (but RP > 70 ms) in infancy and a possible accessory pathway was considered. In contrast to previous studies, we could not uncover any evidence in our case that suggested automaticity in the supraventricular tachycardia mechanism. The short-term cessation of tachycardia with adenosine often indicates an AV node-involving tachycardia, and considering the patient’s age, atrioventricular re-entrant tachycardia was primarily suspected. However, we do not have any evidence, such as an electrophysiological study, that can show that our patient is not adenosine-sensitive ectopic atrial tachycardia. However, excluding EAT is difficult. The fact that the tachycardia ends (spontaneous and with adenosine) with a p wave also supports AVRT.
In previous publications, ivabradine was frequently used successfully in automaticity-related tachyarrhythmias in children, but no reentry-related publications were found in the literature. Therefore, although the mechanism of action of ivabradine is not clearly known in our patient, it may be related to its effect on the funny channels in the atrioventricular node. There are studies showing that this method is successful in providing rate control in the treatment of atrial fibrillation in adult patients. Reference Fontenla, Tamargo and Salgado9 In addition, there are studies showing that it has an effect on the intrinsic autonomic nervous system of the heart. Reference Kamisah and Che Hassan10 We think that it may have been successful in our patient by affecting the atrioventricular node conduction properties in this way.
Ivabradine has been proven to be safe and effective in numerous publications when used for the treatment of congenital junctional ectopic tachycardia in children and postoperative tachycardia. Reference Ergul, Ozturk, Ozgur, Ozyurt, Cilsal and Guzeltas2,Reference Krishna, Kunde, Kumar and Balaji7,Reference Arvind, Kothari and Juneja8,Reference Di Marco, De Nigris, Pepe, Pagano, Di Nardo and Tipo11 In recent years, the literature has been filled with more case reports and series about its use to treatment of focal atrial tachycardia in children; some articles even propose that it can be used as monotherapy. Reference Xu, Guo, Gao, Huang, Liu and Li6 Furthermore, a case report was made of a patient with multifocal atrial tachycardia whose p waves stabilised in a single morphology with the use of ivabradine, and sinus rhythm was established with ablation. Reference Cohen, Cohen, Shope, Stollar and Collazo5
In the cases that were reported, bradycardia was the only negative effect that was noted. Bradycardia has mostly been described in cases when patients have received combined antiarrhythmic drugs. Reference Hackett, Lin and Imundo3,Reference Tolani, Ramdat Misier and Alqahtani12 No serious side effects were observed in a newborn who was mistakenly given 10 times the dose of ivabradine, except for bradycardia, which resolved after 28 hours. Reference Doctor, Scott, Tindel and Nguyen13 We did not observe any significant side effects in our patient. Only asymptomatic bradycardia was observed without haemodynamic significance. Bradycardia was not observed after the beta blocker was discontinued.
Consequently, ivabradine treatment has been shown to produce positive outcomes in automaticity-related supraventricular tachycardias, even at the newborn stage. Ivabradine was used to treat resistant supraventricular tachycardia in our case, despite the lack of evidence supporting automaticity. No negative side effects were reported. In the literature, bradycardia is the only negative effect that has been documented. Randomised controlled trials are required to determine whether or not to use it routinely in treating children with supraventricular tachycardia.
Financial support
None.
Competing interests
The authors declare that there is no conflict of interest.
