Atrial Septal Defect Associated With Right Bundle Branch Block Masking Brugada Syndrome

Abstract

A type 1 Brugada electrocardiogram pattern may be masked by typical right bundle branch block aspect. We present 2 cases (male patients, aged 18 and 22 years) of associated ostium secundum atrial septal defect with a right bundle branch block aspect and symptomatic confirmed Brugada syndrome. Both patients underwent cardiac defibrillator implantation. (Level of Difficulty: Advanced.)

Graphical abstract

Brugada syndrome (BS) is a rare cardiac arrhythmia disease leading to an increased risk of sudden cardiac death (SCD), in the absence of structural heart abnormalities. The typical electrocardiogram (ECG) pattern, known as type 1, includes a J-wave elevation of >2 mV with coved-type ST-segment elevation and T-wave inversion in at least one right precordial ECG lead, V₁ or V₂, positioned in the second, third, or fourth intercostal space.¹ This pattern can be masked by an associated right bundle branch block (RBBB) aspect on surface ECG, leading to a challenging BS diagnosis.^2,3 We report here 2 cases of symptomatic confirmed BS associated with atrial septal defect (ASD) and typical RBBB ECG aspect.

Learning Objectives

• •To highlight that the RBBB ECG aspect can mask the BS ECG pattern.
• •To show that BS can be diagnosed with a typical RBBB pattern.
• •To emphasize that BS can be associated with an ASD.
• •To show that for both patients with ASD and BS, an SCN5A gene mutation was found.

Case Series

Patient 1

A young male patient had a history of ostium secundum ASD, with no family history of heart disease or SCD. He underwent ASD percutaneous closure at 12 years of age with a percutaneous septal device occluder. Standard ECG during follow-up showed typical complete RBBB with an rsR′ aspect in V₁, without a Brugada ECG pattern (Figure 1).

Figure 1.

Baseline 12-Lead ECG of Patient 1

The complete right bundle branch block with rsR′ aspect in V₁, normal axis, inverted T waves in V₁-V₂-V₃, and absence of J point elevation in right precordial leads are shown. Note the junctional rhythm with isorhythmic atrioventricular dissociation. ECG = electrocardiogram.

At 22 years of age, the patient experienced a cardiac arrest at the airport. The external defibrillator recorded ventricular fibrillation successfully treated by external electric shock. Immediately after resuscitation, the patient’s ECG recorded a 40 beats/min bradycardia with junctional escape rhythm and type 1 Brugada ECG pattern (Figure 2).

Figure 2.

Twelve-Lead ECG of Patient 1 Immediately After Resuscitation

Type 1 Brugada pattern on electrocardiogram (ECG) with >2 mm J-wave elevation in V₁-V₂-V₃. Note the sinus node dysfunction with junctional escape rhythm.

Transthoracic echocardiography (TTE) revealed a moderate dilation of the right ventricle with normal right ventricular ejection fraction. Left ventricular ejection fraction was 52% without residual interatrial shunt. Cardiac magnetic resonance imaging did not reveal any signal abnormality on the left or right ventricle. Coronary computed tomography scan was normal.

A dual-chamber implantable cardioverter-defibrillator (ICD) was inserted for secondary prevention of SCD and atrial pacing given the associated sinus node dysfunction. During the following 3 months, 2 episodes of ventricular fibrillation were treated by the ICD (Figure 3). Treatment with hydroxyquinidine was introduced, allowing the absence of ventricular arrhythmia recurrence during a 3-year follow-up.

Figure 3.

Patient 1 ECG Monitoring During Recurrence of Ventricular Fibrillation

ECG = electrocardiogram.

The genetic evaluation found a class V variant in the SCN5A gene, located in a region of chromosome 3p22. There was no other associated genetic mutation, especially any associated with ASD.

Patient 2

An 18-year-old man underwent consultation for dyspnea and syncope. His brother had undergone implantation of a subcutaneous ICD for secondary prevention with BS diagnosis, and his father had experienced a sudden cardiac death of unknown cause at age 38 years.

The patient’s baseline 12-lead surface ECG revealed an atypical incomplete RBBB aspect leading to BS suspicion (Figure 4). A flecainide test was therefore performed, unmasking a type 1 Brugada ECG aspect (Figure 5).

Figure 4.

Baseline 12-Lead ECG of Patient 2

The incomplete right bundle branch block aspect, inverted T-wave in V₁, and absence of ST-segment elevation are shown. ECG = electrocardiogram.

Figure 5.

Patient 2 Flecainide Test Inducing Type 1 Brugada ECG Pattern

12-lead electrocardiogram (ECG) before (left) and during (right) flecainide perfusion.

TTE found an ostium secundum ASD with major interatrial shunt and right cavities’ dilation. A percutaneous septal device occluder was therefore implanted, with clear benefit on the patient’s symptoms. Postprocedural TTE did not find any residual interatrial communication.

Given the presence of typical cardiac syncope, the patient underwent implantation of a subcutaneous ICD.¹ A subcutaneous ICD was preferred due to the absence of any documented significant electrical conduction abnormality.

Genetic testing also found a mutation in the SCN5A gene, located in a region of chromosome 3p22.

Discussion

BS is an autosomal dominant channelopathy affecting young subjects with a structurally normal heart, associated with a high risk of SCD. Its penetrance is variable, and the stratification of the risk of sudden death is difficult. The diagnosis is electrocardiographic with an incomplete atypical RBBB pattern and a J-wave elevation >2 mm in at least one right precordial lead, spontaneously or induced by sodium channel inhibitors (eg, flecainide),^1,4 and a coved ST-segment elevation aspect.

The typical RBBB aspect on ECG is defined as QRS duration ≥80 milliseconds; rsr′, rsR′, or rSR′ aspect in leads V₁ or V₂; and an S-wave of greater duration than the R wave or >40 milliseconds in leads I and V₆.⁵

The real RBBB aspect can mask the BS diagnosis on surface ECG. We report here 2 cases of ASD causing an RBBB ECG aspect associated with BS. Electrocardiographically, ASD isolated or associated with other congenital heart diseases often manifests as complete or incomplete RBBB and left- or right-axis deviation depending on whether the ASD is ostium primum or secundum, respectively. These are mostly signs of overload of the right cavities.⁶

Wada et al² found that up to 8% of patients with BS can present an associated complete RBBB without underlying heart disease, which may lead to an underdiagnosis of BS. Thus, a BS diagnosis could be challenging in the presence of ASD, a cause of RBBB due to overload of the right cavities. Notably, Tsuchihashi et al⁷ described a case report associating ASD with BS. Baseline ECG exhibited a first-degree atrioventricular block and incomplete RBBB. Concomitant to fever occurrence, the ECG unmasked a type 1 Brugada pattern.

Chiale et al⁸ elegantly described a proposal to reduce wide QRS RBBB aspect with anticipated right ventricular pacing causing QRS fusion unmasking BS ECG aspect.

Interestingly, in our 2 cases, a genetic mutation associated with BS was found. Mutations in 10 genes have been identified as responsible for BS. They encode for subunits of the cardiac sodium, potassium, and calcium channels, as well as genes involved in the trafficking or regulation of these channels. The mutation of the SCN5A gene located in the 3p22 region, responsible for coding sodium channels, is found in 15% to 30% of BS.⁴

Most ASD are sporadic and result from spontaneous genetic mutations. However, hereditary forms have been reported. Familial ostium secundum abnormalities may be associated with mutations in the transcription factors NKX2.5 (5q34), GATA4 (8p23.1), and TBX6 (16p11.2), as well as conduction disorders.⁹ Our patients had no mutations in the aforementioned genes. Meregalli et al¹⁰ identified a genetic polymorphism leading to increased mortality, but to date no genetic mutation has been described linking ASD and BS.

Conclusions

We described 2 cases of BS associated with ASD causing RBBB aspect in 2 young men with ventricular arrhythmia risk factors. Both cases concerned men with an SCN5A gene mutation. The BS ECG pattern diagnosis was possible on a surface ECG even when associated with an RBBB ECG aspect. If a patient experienced cardiopulmonary arrest due to lethal ventricular tachyarrhythmia and complete RBBB on 12-lead ECG, we should consider the probability of cardiomyopathy such as arrhythmogenic right ventricular cardiomyopathy and BS.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.