Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery

Abstract

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.

Introduction

Junctional ectopic tachycardia (JET) usually originates from atrioventricular node, atrioventricular junction, or bundle of His complex. Postoperative JET is mostly seen within 72 h after pediatric cardiac surgery. The incidence of postoperative JET is found to be 2–10% of cases [1, 2].

Risk factors for JET include sustained ischemia time and cardiopulmonary bypass (CPB) time, infants less than 6 months, hypoxia, electrolyte imbalance, surgery involving area near atrioventricular node, use of increased doses of ionotropic agents, defective filling of the ventricles, and atrioventricular asynchrony [2].

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis, atrioventricular canal (AV) canal, and ventricular septal defect repair, arterial switch operation, Norwood procedure, and interrupted aortic arch repair are mainly responsible for JET [3].

Plausible reason of etiopathogenesis of JET includes expanded automaticity that is caused within the bundle of His due to direct trauma or edema by sutures or infiltrative hemorrhage to bundle of His and the AV node [2, 3].

JET is typically characterized with a heart rate of more than 170 beats per min along with a narrow complex rhythm which is consistently characterized by atrioventricular dissociation or 1:1 pattern of retrograde atrial conduction [1–3]. Diversified antiarrhythmic agents such as propranolol, magnesium, flecainide, and amiodarone have been used in an impressive way, alone or in combination to treat JET, but showed suboptimal efficacy and varied associated adverse effects [1–3]. Ivabradine acts by inhibiting funny current channels (if current) that involve hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels. These channels play a significant role in generation of junctional tachycardia. Ivabradine selectively inhibits HCN4 channels and has produced satisfactory results in treating JET. Additionally, it is hemodynamically neutral thus exemplify as potential frontier in treating tachyarrhythmias [4].

Case report

We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. All the patients underwent intracardiac repair using cardiopulmonary bypass with bicaval cannulation, with core cooled to 26 °C. Antegrade cardioplegia using del Nido cardioplegia solution was used and half dose was repeated if duration of cross clamp exceeded 90 min. The usual inotropes used were dobutamine of 5 μg/kg/min and adrenaline of 01 μg/kg/min. The first approach with the onset of JET was core cooling to 35 °C and administration of magnesium (25 mg/kg). If there was no response in 2 h time, ivabradine was started. Details regarding cases are depicted in Table 1.

Table 1.

Detailed information of cases with postoperative JET treated with ivabradine

Age/weight and sex	Diagnosis and procedure	Time from end of surgery to JET onset Maximum heart rate	CPB duration and cross clamp duration	Ivabradine starting dose and time to respond (HR < 150 bpm)	Recurrence Number of doses required	Final outcome and complications
6 months 5.8 kg Male	TOF with severe infundibular and valvar stenosis Intracardiac repair with transannular patch	8 h 196 bpm	110 min 75 min	0.1 mg/kg/dose 0.6 mg 3 h	No recurrence 1 dose	Sinus rhythm return on day 2 Uneventful course Discharged home on day 7
8 months 7 kg Male	Double outlet right ventricle with severe MPA hypoplasia and LPA origin stenosis Intracardiac repair with double-barrel right ventricular reconstruction	6 h 200 bpm	240 min 100 min	0.1 mg/kg/dose 0.7 mg 2 h	No recurrence 1 dose	Return of sinus rhythm on day 2 Uneventful course Discharged on day 10
4 months 3.5 kg Female	Complete atrioventricular canal defect Intracardiac repair using 2-patch technique	4 h 210 bpm	180 min 120 min	0.2 mg/kg/dose 0.7 mg 4 h	Recurrence on day 1 controlled with another repeat dose in 2 h 2 doses	Return of sinus rhythm on day 4 Discharged on day 14, prolonged stay due to sepsis
8 months 5 kg Female	Supracardiac TAPVC with double outlet right ventricle Intracardiac repair—posterior approach to repair of supracardiac TAPVC	8 h 190 bpm 90 min	130 min 90 min	0.2 mg/kg/dose 1 mg 2 h	No recurrence Needed pacing for about 6 h when heart rate went to < 100/min 6 h post ivabradine 1 dose	Sinus rhythm return on day 1 Discharged on day 7

Abbreviations: CPB, cardiopulmonary bypass; HR, heart rate; bpm, beats per minute; MPA, main pulmonary artery; LPA, left pulmonary artery; TAPVC, total anomalous pulmonary venous connections

Discussion

In accordance with previously published literature, we could also find a satisfactory role of ivabradine in JET. Previously amiodarone 15 μg/kg/min bolus and 5 μg/kg/min infusion were used to rectify JET but recently ivabradine has changed the scenario owing to its specific mechanism of action and minimal side effects. We used ivabradine in a dose of 0.1 to 0.2 mg/kg/dose. There is flourishing data in support of successful use of ivabradine in postoperative JET. A preliminary study has suggested importance of ivabradine as an adjunct for refractory junctional ectopic tachycardia following pediatric cardiac surgery. Kumar et al. used oral ivabradine among 5 patients in the dose range of 0.1 to 0.2 mg/kg/12 h as an adjunct to amiodarone to treat refractory JET. Rate reduction was gained in all five patients and sinus rhythm was achieved during a mean duration of 31.6 ± 13.6 h. Any recurrence of JET, hemodynamic derangement, or any other side effects attributable to oral ivabradine were not documented [5].

Another study on eight patients with postoperative JET noted that all eight patients responded to ivabradine. Recurrence of JET was found 10 h after ivabradine in one patient, but remission to sinus rhythm occurred after administering amiodarone along with the second dose of ivabradine [6].

In our study also, recurrence occurred in 1 patient on day 1 but it was controlled by repeating the dose of ivabradine and return of sinus rhythm was observed on day 4.

Boulos et al. portrayed the use of ivabradine in malignant JET in infants following congenital heart surgery. The arrhythmia in their case of malignant JET was controlled only by oral ivabradine 0.1 mg/kg/day in bis in die (BID) after the failure of conventional therapy [7]. Other studies also intensified the evidence of use of ivabradine in JET [8, 9]. No cardiac adverse effects attributable to ivabradine were noticed in previous studies, but we encountered bradycardia in one case and required pacing [10].

The total anomalous pulmonary venous connections (TAPVC) case was operated using the “Schumaker” technique, where the heart is kept in situ and a transverse incision is made on the posterior right atrial (RA) wall across the septum into the left atrium and is anastomosed to an incision on the common chamber. This particular case had a very small left atrium and very hypertrophied RA wall and a difficult anatomy with vertical vein going to the right behind the right pulmonary artery and entering above the azygous vein and considerable retraction of the tricuspid valve and RA was required to be able to proceed with the anastomosis.

We experienced that the incidence of JET is related to amount of stretching of the tricuspid valve, and we have also noticed that incidence is proportional to the difficulty in exposure of the defect through the tricuspid valve.

We have also noticed a decrease in JET after beginning to use dexmedetomidine for initial postoperative sedation, and we tried to use of strategic sutures to avoid traction on the tricuspid valve.

If there is JET, our protocol now is to use hypothermia, magnesium, reduction of inotropes if tolerated, and ivabradine in a dose of 0.1 mg/kg. We observe the patient for 2 h and repeat another dose of ivabradine 0.1 mg/kg in case of no response. The pacing wires are kept connected to a pacemaker chamber. Once the rhythm returns to sinus rhythm or is controlled, we do not repeat the dose. In patients with heart failure, even with prolonged use of ivabradine, we have not noticed major complications. We have not felt the need to continue the dose, beyond intensive care unit (ICU) setting when the indication for use is postoperative JET.

The decision to use ivabradine was made due to increasing experience with this drug in heart failure population including pediatric heart failure patients, where we had no major complications and the drug seemed to be well tolerated.

Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine. The absence of an intravenous (IV) formulation and the unknown effect of a postoperative low cardiac output state on drug absorption are major limitations of ivabradine in treating JET.

Conclusion

Nevertheless, randomized controlled trials were not yet reported but the importance of ivabradine in JET as published in some case reports and case series cannot be neglected. Our study will intensify the perception of use of ivabradine in JET. We suggest more randomized controlled trials should justify its efficacy in JET distinctively in pediatric population.

Funding

This study was not funded.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Animal and Human Rights Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.