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Ann Thorac Surg 2003;76:148-151
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Intravenous flecainide for the treatment of junctional ectopic tachycardia after surgery for congenital heart disease

^a Pediatric Cardiology and Cardiac Surgery, University of Bologna, Bologna, Italy
^b Pediatric Cardiac Intensive Care Unit, University of Bologna, Bologna, Italy

Accepted for publication January 26, 2003.

^* Address reprint requests to Dr Bronzetti, Pediatric Cardiology, University of Bologna, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138, Bologna, Italy.
e-mail: gabronz{at}hotmail.com

	Abstract

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BACKGROUND: Junctional ectopic tachycardia (JET) is a life-threatening arrhythmia producing severe hemodynamic dysfunction, which may complicate the postoperative course of surgery for congenital heart disease. Strict care and a fast and effective antiarrhythmic strategy are essential, because mortality largely depends on the duration of the arrhythmia.

METHODS: Seven consecutive neonates with postoperative JET without any evidence of myocardial ischemia received intravenous flecainide after conventional therapies proved ineffective. Atrial pacing at the minimal rate for atrioventricular synchrony was followed by a 10-min intravenous infusion of 1.6 mg/kg flecainide, then continuous infusion of 0.4 mg/kg flecainide per hour. Treatment was considered effective based on restoration of sinus rhythm or a JET rate no higher than 170 bpm within 4 hours of flecainide loading. Overall mean flecainide infusion lasted 31.2 hours (range 25 to 53 hours). Side effects were assessed by monitoring plasma flecainide levels, electrocardiogram, arterial pressure, and central venous pressure.

RESULTS: Flecainide was effective in all 7 patients after an infusion duration of 3.6 ± 1.5 hours. Sinus rhythm was restored after 7.2 ± 9.7 hours. After 4 hours of loading, heart rate fell from 219 ± 14 to 136 ± 7 bpm (p < 0.0001), arterial pressure increased from 69 ± 8 to 93 ± 10 mm Hg (p < 0.0001), while central venous pressure decreased from 8.0 ± 1.6 to 5.2 ± 1.9 mm Hg (p = 0.0007). No side effect or recurrence was noted.

CONCLUSIONS: Flecainide can exert a fast antiarrhythmic effect on postoperative JET, and its infusion can be modulated to maintain the concentration within the therapeutic range, thus avoiding toxicity. We propose further consideration of flecainide for treatment of JET in neonates without myocardial ischemia.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Junctional ectopic tachycardia (JET) is an uncommon arrhythmia thought to arise from abnormal automaticity of the atrioventricular (AV) node or proximal His bundle [1, 2], and in children JET is seen more often as a transient phenomenon immediately after intracardiac surgery for congenital heart defects [3, 4]. In the postoperative setting, rapid JET can lead to severe hemodynamic compromise and death. However, if the patient can be supported by restoring AV synchrony and slowing the junctional rate to the physiologic range, JET usually resolves within a few days. Postoperative JET can be related to increased histamine liberation induced by cardiopulmonary bypass (CPB) or deep hypothermia [5]. Furthermore, mechanical damage to or hemorrhage within the conduction tissue [6] may result in or be associated with an arrhythmogenic focus [7].

Flecainide, because of its electrophysiological properties, can decrease the automaticity of any arrhythmogenic focus, including the one involved in JET. However, despite a strong rationale for the use of flecainide for managing postoperative JET, limited experience and concerns regarding toxicity has limited such use [8].

We report our experience with intravenous flecainide for JET in 7 patients who underwent operations for congenital heart defects.

	Patients and methods

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Patients
Of the 382 patients operated for congenital heart defects between January 2000 and November 2001, 34 patients (9%) developed an early postoperative tachyarrhythmia. Of those, 7 patients (2%) developed JET during the postoperative course (median 2 days, range 1 to 6 days). Details are presented in Table 1. All the operations were performed by the same surgeon using hypothermic CPB at 24°C of esophageal temperature and blood cold cardioplegia. Preoperatively, all patients affected by transposition of the great arteries (TGA) underwent balloon atrial septostomy and antegrade aortography. Surgical repair was undertaken within a few days.

After the initial conventional management proved ineffective, atrial pacing was performed at the minimal rate for effective AV synchrony and intravenous infusion of flecainide was started. Before the year 2000 the management strategy for postoperative JET was heterogeneous (atrial pacing, propafenone, or amiodarone). Until 1999, atrial pacing represented the only treatment provided for our JET patients, producing mixed results. The flecainide infusion protocol consisted of a 1- to 2-mg/kg bolus (mean 1.6 ± 0.5 mg/kg) for more than 10 minutes followed by a continuous infusion of 0.40 mg/kg per hour. During the study period, the initial loading dose was raised from 1 mg/kg (patients 1 to 3) to 2 mg/kg (patients 4 to 7) in accordance with our increasing confidence with flecainide. Serum levels of flecainide were assessed after 24 hours and the infusion rate was modified accordingly with the aim of reaching stable plasma concentrations within the therapeutic range (200 to 1000 ng/mL). Atrial pacing was stopped frequently during the first 4 hours and every 4 hours thereafter to evaluate the termination of JET or the reduction of heart rate. Flecainide infusion was continued until the restoration of stable sinus rhythm for at least 24 hours. Overall mean flecainide infusion lasted 31.2 hours (range 25 to 53 hours).

In an effort to minimize the influence of spontaneous JET resolution on study data, effective therapy was strictly defined as either a decreased JET rate to less than 170 bpm within 4 hours of flecainide infusion or conversion to sinus rhythm at surface ECG within 24 hours of infusion.

Side-effects monitoring consisted of continuous ECG, arterial pressure and central venous pressure monitoring, and flecainide plasma sampling to avoid drug levels out of the therapeutic range. Data were collected retrospectively from patient records, operative notes, intensive care unit data sheets, and postoperative ECGs.

Statistical analysis
Statistical analysis was performed with Wilcoxon matched pairs test using StatView 5.0 (SAS Institute, Cary, NC). Data are presented as mean value ± SD along with range values when appropriate. A level of p less than 0.05 was considered significant.

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Flecainide was effective in all 7 patients after a mean infusion time of 3.6 ± 1.5 hours (range 1 to 6 hours) with restoration of sinus rhythm after a mean time of 7.2 ± 9.7 hours (range 1 to 29 hours) (Table 1). After 4 hours of infusion, mean heart rate fell from 219 ± 14 bpm (range 195 to 234 bpm) to 136 ± 7 bpm (range 125 to 148 bpm) (p < 0.0001) (Fig 1). Mean maintenance dose needed to achieve therapeutic effect was 0.4 mg/kg per hour (range 0.38 to 0.42 mg/kg per hour) with a mean flecainide serum level after 24 hours of 398 ± 142 ng/mL (range 276 to 682 ng/mL). No patient experienced side effects related to flecainide therapy or proarrhythmic effects. After 4 hours of flecainide infusion, hemodynamic status was markedly improved with a rise of systolic arterial pressure from 69 ± 8 to 93 ± 10 mm Hg (p < 0.0001) and a fall of central venous pressure from 8.0 ± 1.6 to 5.2 ± 1.9 mm Hg (p = 0.0007). No recurrence of JET was observed after flecainide discontinuation, supporting the self-limiting nature of this condition.

View larger version (15K): [in this window] [in a new window]   Fig 1. Heart rate deceleration (mean ± SD) after 2 and 4 hours of flecainide infusion.

	Comment

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The many interventions that have been used previously for postoperative JET all have important drawbacks. Although use of procainamide plus hypothermia can produce an efficacy rate of 80% [9], such therapy was associated with a lethal complication rate as high as 10% [10]. Oral propafenone has been associated with a 5% incidence of adverse cardiac events among patients with structural heart disease [11]. Moreover, a 14% mortality rate was reported in a small series of children who received intravenous propafenone for acute postoperative JET [12].

Use of intravenous amiodarone is a more recent approach [13, 14]. However, despite excellent efficacy rates (up to 93%), serious complications have emerged [15, 16] despite therapeutic or subtherapeutic levels. Furthermore, use of amiodarone seems to be associated with prolonged hospitalization and mechanical ventilation time [17]. This increased JET morbidity [17] is likely to depend on both the severity of the disease and the latency between amiodarone administration and its clinical efficacy. The unpredictable adverse effects of amiodarone and the need for a faster and more efficient arrhythmic conversion led us to consider flecainide as a potentially attractive treatment for postoperative JET.

In contrast to amiodarone [18], optimal plasmatic concentrations of flecainide are promptly achieved after the initial 30 minutes after infusion [19] with a high early uptake from the myocardial tissue and a prompt antiarrhythmic effect [20]. In our population, response to flecainide was rapid with conversion to sinus rhythm within 1 to 29 hours (average 7 hours) in all patients. Furthermore, only 2 patients remained in JET after 4 hours, both with an heart rate of less than 170 bpm, and a significant hemodynamic improvement was noted in all patients after 4 hours of infusion.

Another potential advantage of flecainide is its dosability. Therapeutic concentrations can be readily monitored by routine blood sampling, thereby helping to avoid toxicity, especially in patients with underlying heart disease [21]. However, such a risk seems much less likely for patients with JET receiving intensive care in which continuous monitoring allows the prompt recognition and treatment of any life-threatening condition.

Although surgical repair in patients with simple TGA does not directly involve the AV node region or seem to be strictly related to JET development, JET developed in 5 patients after simple TGA repair. Mechanical injuries produced by the atrial septostomy balloon and anterograde aortography catheter on the AV node area may have played a role. Furthermore, CBP can directly trigger postoperative JET [5].

None of our patients had any ECG or biochemical evidence of myocardial ischemia, which may trigger the onset of life-threatening arrhythmias and their substantial increase in mortality [22]. Therefore, we would not recommend flecainide when myocardial ischemia is suspected. We are aware that the lack of a control group may be a limit of the study. However, we endorse the use of flecainide for the treatment of postoperative JET, with initial loading of 1 to 2 mg/kg, followed by continuous infusion of 0.4 mg/kg per hour and continuous monitoring of ECG and hemodynamic variables.

In conclusion, this limited experience prompts us to propose consideration of flecainide as an effective and apparently safe front-line strategy for the treatment of JET secondary to repair of congenital heart defects in patients with no evidence of myocardial ischemia. Drug administration should be initiated in the intensive care unit with continuous monitoring of the heart rhythm and cardiac function.

	Acknowledgments

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Gabriele Bronzetti, MD, is funded by a grant from the Italian Federation of Cardiology.

The authors are grateful to Robin M. T. Cooke for scientific editing.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Roberto Formigari Alessandro Giardini Gaetano Gargiulo Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bronzetti, G. Articles by Picchio, F. M. Search for Related Content PubMed PubMed Citation Articles by Bronzetti, G. Articles by Picchio, F. M. Related Collections Electrophysiology - arrhythmias