Correspondence *Pediatric Cardiology Department, Bambino Gesù Hospital, Piazza Sant'Onofrio 4, Rome 00165, Italy

Email drago@OPBG.net

The case

A 9-year-old boy began experiencing episodes of sudden paleness and mild dizziness after meals, and displayed a slightly reduced tolerance to exercise. He was assessed before partaking in sport and was shown, on electrocardiography, to be in junctional rhythm. He was subsequently referred to a specialist institution for evaluation and eventual treatment.

The child had no siblings. His parents were not consanguineous, and neither had abnormal electrocardiograms. There was no family history of sinus node dysfunction (SND). The child had no personal history of surgery, recent infections, head trauma, pharmacological treatment or syncope, and had not taken any medication of note. The results of physical examination at presentation were normal, as were his neurological status and muscle tone. Electrocardiography showed a junctional rhythm with a heart rate of 74 beats/min, and no signs of atrial activation (Figure 1A). Twenty-four-hour Holter monitoring, performed twice consecutively, confirmed the total absence of P waves and the constant presence of a junctional rhythm alternating with an idioventricular rhythm (Figure 1B). The mean heart rate during monitoring was 48 beats/min (range 38–110 beats/min).

Figure 1 Electrocardiograms demonstrating the total absence of atrial activity

(A) At baseline. (B) During 24 h Holter monitoring. Alternation between junctional and idioventricular rhythm was observed, without any apparent atrial activity. No P waves were evident. (C) During treadmill stress testing, at the peak of exercise. Again, there was no evidence of atrial automaticity.

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Echocardiography of the patient did not show any structural heart defects. Left atrial and ventricular dimensions were in the upper range of normal values (end diastolic left ventricular diameter 42 mm; end systolic left ventricular diameter 22 mm; and left atrial diameter 23 mm). The left ventriclar shortening fraction was 48% and the ejection fraction was 78%. Atrial contractility was present, and Doppler evaluation of mitral blood flow showed fusion of the E and A waves.

On treadmill exercise stress testing the patient's heart rate was slow to increase and reached a maximum of 132 beats/min at the peak of exercise, which is low for his age group (the normal value [mean SD], obtained in the same exercise laboratory from a healthy population, was 195 11 beats/min).¹ His exercise tolerance was normal but in the lower limits (11.9 min; normal values [mean SD] 14.4 2.6 min).¹ Only junctional rhythm was observed during the test (Figure 1C). There was a sudden decrease in heart rate within the first minute of the recovery phase—from 132 beats/min to 58 beats/min in approximately 30 s.

The patient underwent an intracardiac electrophysiological study and three-dimensional (3D) electroanatomical mapping of the right atrium performed with the CARTO^® XP Navigation System and a QwikStar^® 7F mapping and ablation catheter (Cordis Corporation, Miami Lakes, FL).² The procedures were performed under general anesthesia induced with sevoflurane and propofol, and maintained with sevoflurane or isoflurane. No pharmacological testing (with atropine or isoprenaline, for example) was performed during the electrophysiological study. During anesthesia the patient was in idioventricular rhythm (left bundle branch block morphology) with a heart rate of 40 beats/min.

The 3D mapping showed a retrograde and homogeneous activation of the right atrium that originated from the atrioventricular junction, with normal 1:1 ventriculoatrial retrograde conduction (Figure 2). The bipolar voltage map was homogeneous and showed normal amplitude, except for a reduced voltage (0.1–0.5 mV) in the posterior zone between the superior and the inferior vena cava. Atrial pacing—performed inside the right atrial appendage—resulted in normal atrium capture (the capture threshold of the pacing wire was <1 mV/0.5 ms) and showed a normal atrioventricular conduction with a Wenckebach point of 400 ms (Figure 3). The recovery time of the idioventricular rhythm was 6 s.

Figure 2 Three-dimensional electroanatomical maps of the patient's right atrium, performed with the CARTO^® XP Navigation System (Cordis Corporation, Miami Lakes, FL)

(A) Left anterior-oblique and (B) anterior-posterior views demonstrating the different activation times across the atrium. The intra-atrial conduction speed was 135 ms. (C) Left anterior-oblique and (D) posterior-anterior views demonstrating areas with a potential greater then 0.5 mV—represented in pink. Abbreviations: AP, anterior–posterior; HIS, bundle of His; LAO, left anterior–oblique; LAT, lateral; PA, posterior–anterior.

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Figure 3 Sequential three-dimensional bipolar voltage maps of the patient's right atrium, demonstrating the progression of electrical activation (shown in red) in this chamber

Images proceed from left to right.

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Genetic tests (denaturating high-performance liquid chromatography and direct sequencing of abnormal conformers) were negative for mutations in SCN5A, the gene encoding the alpha subunit of the Na_v1.5 human cardiac sodium channel.

Pacemaker implantation was postponed because of the young age of the patient and the mild nature of his symptoms. At 15 months' follow-up the patient was in the same clinical condition and no other signs or symptoms had developed. Electrocardiography and Holter monitoring, repeated every 6 months, showed continued alternation between junctional and idioventricular rhythm with no apparent P waves.

Discussion of diagnosis

SND, also known as sick sinus syndrome, comprises a wide spectrum of arrhythmias and is characterized by abnormalities of sinus node automaticity, sinoatrial conduction or autonomic regulation of the sinus node. The condition is rare in children and is often asymptomatic.³ Primary causes of SND in pediatric patients include congenital heart defects (such as atrial septal defect or left atrial isomerism), neuromuscular diseases (such as Friedreich's ataxia) and cardiomyopathies, although the condition can occur in patients with an otherwise normal heart.⁴ Secondary causes of pediatric SND include surgical repair or palliation of congenital heart diseases, neonatal hypoxia, diseases of the central nervous system, hypervagotonia and hemochromatosis.⁴

A recessive disorder caused by mutations in SCN5A has been described in some cases of idiopathic, congenital and familial SND.⁵ Loss of function of the cardiac sodium channel decreases the conductivity of the atrial myocardium and could lead to conduction failures between adjacent cells—a plausible mechanism to explain SND in patients with this channelopathy.^{6, 7}

Mutations in SCN5A can cause atrial standstill, which also falls under the diagnosis of SND. This is a rare arrhythmogenic disorder, which is characterized by the complete or partial absence of electrical and mechanical activity in the atria—either transient or persistent. Atrial standstill is associated with severe damage to the atrial myocardial cells, nerves or arteries, and can be secondary to amyloidosis, Emery–Dreifuss muscular dystrophy (X-linked), Kugelberg–Welander syndrome (autosomal recessive) or Ebstein's anomaly.⁸ The condition can be familial, sporadic or idiopathic.

Reduced sinus node activity can also be found in patients with long QT syndrome.⁹ In patients with type 4 long QT syndrome, SND has been reported owing to a mutation in the gene ANK2, which encodes the membrane protein ankyrin-B.^{10, 11} Isolated cases of SND have also been reported in association with de novo mutations of HCN4, which encodes the hyperpolarization-activated cyclic nucleotide-gated potassium channel 4.¹²

In children, a diagnosis of SND can be made if at least one of the following criteria is evident on electrocardiography: sinus bradycardia, severe sinus arrhythmia, sinus pause or arrest, slow escape rhythms, sinoatrial exit block (second degree types I and II), bradyarrhythmias or tachyarrhythmias, sinus node re-entry tachycardia and atrial muscle re-entry tachycardia.² Two or more of these abnormalities can coexist in the same patient.

In the patient described in this report there was no evidence of atrial activity on any electrocardiogram, nor during Holter monitoring or during exercise stress testing. The atrioventricular node showed reduced automaticity, as demonstrated by the presence of a slow ventricular escape rhythm with a very long recovery time seen during Holter monitoring and the electrophysiological study. The atrial cells demonstrated a normal depolarization capacity on endocardial stimulation, suggesting that atrial standstill was not the pathology in this patient.

The presence of a fibrous right atrium could have been responsible for the defect in atrial conduction and automaticity in this case, and 3D electroanatomical mapping was performed to better evaluate atrial activation, the modality of intra-atrial conduction, and the characteristics of the atrial musculature. The CARTO^® XP Navigation System enables precise real-time monitoring of the position and orientation of the mapping catheter while performing intracavitary electrocardiography, thereby enabling the creation of an electroanatomical color-coded map.¹³ The findings demonstrated the presence of a normal atrial musculature, thereby precluding fibrous right atrium as a potential cause for the absence of atrial automaticity in this patient (Figure 2). Atrioventricular conduction during atrial pacing was normal with a Wenckebach point of 400 ms, which can be considered typical in deeply anesthetized pediatric patients.^{14, 15}

Genetic tests were negative for mutations in SCN5A, and the cause of SND in this case remains unclear. We might speculate that an isolated mutation in the genes encoding calcium channels could be responsible for this defect of automaticity, but further tests are needed to clarify the underlying pathological mechanisms.

Treatment and management

The electrophysiological characteristics of this patient suggested that he might benefit from the implantation of an endocardial single-chamber atrial pacemaker. The indication was not in class I,¹⁵ however—the symptoms of bradycardia were mild and there were no signs of ventricular failure. Furthermore, the implantation of an endocardial atrial lead in such a young patient could lead to complications such as extreme lead traction during growth. Considering the fact that the risk of sudden cardiac death is extremely low in patients with SND,¹⁵ pacemaker implantation was postponed until after puberty when the patient will have completed his growth. The procedure will only be performed earlier should more-severe symptoms develop.

Conclusions

We report a case of pediatric SND in whom atrial automaticity was absent despite the presence of normal atrial capture and conduction. Further investigations in the patient should clarify whether this pathology was caused by the absence of specialized myocardial cells or by a particular channelopathy.

References

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Subject areas under which this article appears: Arrhythmias | Pathology