Background
Loss-of-function variants of human cardiac sodium channel gene
SCN5A induce a wide range of arrhythmic disorders, such as Brugada syndrome [
1,
2], dilated cardiomyopathy [
3], and progressive cardiac conduction disorder (PCCD, also known as Lev-Lenègre syndrome) [
4], which are known as sodium channelopathies.
Surgical closure for an atrial septal defect (ASD) is a well-established procedure with a good long-term outcome [
5‐
8]. However, postoperative supraventricular tachycardia is a frequent sequela among ASD patients treated by surgical closure [
6,
8].
Here we report the case of a patient with a multiple arrhythmia who carried an SCN5A frameshift mutation with a surgical repair history for ASD. We provide the details of the pathology of this complex case toward to goal of devising a better therapeutic approach.
Discussion and conclusions
We presented a patient with a heterozygous
SCN5A frameshift variant and a history of a surgical ASD closure. The identified variant, p. L1346HfsX38, was not reported previously. Because the frameshift variant was in exon 23 of
SCN5A, which normally consists of 28 exons, we suspected that the variant caused a truncation of mRNA, resulting in the decreased expression level of Nav1.5 due to NMD [
9]. The patient’s sinus bradycardia, cardiac conduction disturbance with severe QRS widening, and ventricular fibrillation were all compatible as phenotypes of Brugada syndrome [
10]. However, type 1 Brugada ECG findings were not evident because of the patient’s complete right bundle brunch block. The fact that the patient’s mother also carried the same variant but remained asymptomatic was not surprising, because 90% of Brugada syndrome patients are male [
10,
11].
In the last decade, the concept that sodium channelopathies are not pure arrhythmogenic disorders but rather are cardiomyopathies with a strong arrhythmogenesis has been widely accepted. An association between these variants and congenital structural heart diseases has not been demonstrated. In our patient’s case, we could not conclude that the patient’s ASD was caused by his SCN5A variant.
Trans-catheter ASD closure with a device has gained acceptance, but surgical closure remains the first-line strategy with excellent long-term outcomes [
8]. Sinus node dysfunction requiring a pacemaker implantation was reported in approx. 4% of patients after a surgical ASD closure in a long-term follow-up study [
12], but severe QRS widening, bundle brunch blocks, and life-threatening ventricular arrhythmias are extremely rare. In our patient’s case, the sinus bradycardia had worsened during 20 years after his ASD surgery, and complete right bundle brunch block with severe QRS widening was observed as well. This drastic change was not plausible as a late complication of surgical repair for ASD.
Postoperative SVT is commonly seen after a cardiac surgery; not only for ASD repair, but for all types of congenital heart disease [
13]. Our patient’s arrhythmia was observed to be circulating around the incision in the right atrium (which is known as incisional tachycardia), and radiofrequency ablation at the top of the incision successfully eliminated the arrhythmia. Due to the impaired cardiac conduction by an
SCN5A variant, this often-observed arrhythmia presented a rare clinical manifestation that was initially difficult to interpret.
The sedation in the intensive care unit possibly triggered his polymorphic VT by worsening bradycardia. However, considering the rapid progression of CCD in the last 2 years, we are convinced that he would have the similar adverse event in very near future even without sedation. When it comes to the choice of implantable cardiac device, although this patient’s polymorphic VT was successfully suppressed by controlling bradycardia, we chose ICD rather than simple DDD pacemaker. It is because of the high inducibility of polymorphic VT by PES from the right ventricle. PES-induced ventricular tachycardia is one of the predictors of lethal events of Brugada syndrome [
14] even though there is still a controversy [
15]. We concluded that ICD implantation was not an overtreatment for this patient’s case.
Currently, 97% of the patient’s heart beats are stimulated by dual chamber pacing by the ICD. At the time of implantation, we did not expect that a setting preferring patient’s intrinsic ventricular beats had a significant advantage over right ventricular stimulation for cardiac synchronicity because his own QRS was extremely widened. However, considering his age, it is also necessary to optimize the pacemaker setting by assessing hemodynamics with or without right ventricular pacing, as well as preventing bradycardia.
As a differential diagnosis, arrhythmogenic right ventricular cardiomyopathy and bundle branch reentry VT can be stated. But cardiac magnetic resonance imaging could not detect late gadolinium-enhancement in either left or right ventricular cardiac muscle. Sustained monomorphic VT, which was suggesting bundle brunch VT, could not be induced by repetitive PES. Furthermore, we detected no genetic variant in desmosomal genes, typical ARVC causative genes.
In conclusion, multiple coexisting arrhythmogenicities induced repetitive arrhythmias difficult to diagnose in our patient with a sodium channelopathy. A precise understanding of this patient’s pathology by a multilateral approach using an ECG analysis, an electrophysiological study, and genetic screening enabled effective combination therapy comprised of catheter ablation and an ICD.
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