EKG Pattern of Brugada Syndrome and Sudden Infant Death Syndrome—Is It Time to Review the Diagnostic Criteria? Case Report and Review of Literature

Abstract

Brugada Syndrome (BrS) is a cardiac disorder characterized by incomplete right bundle‐branch block and ST elevations in the anterior precordial leads especially V₁–V₃, associated with an increased risk for sudden cardiac death (SCD) in young adults. Our case describes a patient with family history of sudden infant death syndrome (SIDS) who presented with a Brugada pattern unmasked by severe hyperkalemia and diabetic ketoacidosis. Several studies have concluded there may be a genetic link among SIDS, SDC, and BrS resulting from mutations in cardiac ion channel‐related genes. Recognizing SIDS as part of the diagnostic criteria for BrS would help us identifying a significant number of families susceptible to develop SCD (as well as SIDS).

Brugada syndrome (BrS) is a cardiac disorder characterized by abnormal electrocardiogram (ECG) findings, associated with an increased risk for ventricular tachyarrhythmias that may lead to syncope, cardiac arrest, or sudden cardiac death (SCD) in young and otherwise healthy adults and, less frequently, in infants and children.1 The typical electrocardiographic pattern is characterized by incomplete right bundle‐branch block and ST elevations in the anterior precordial leads especially V₁–V₃.2

BrS is genetically determined with a high number of gene mutations having been identified.3, 4, 5 In the past, patients with BrS were thought to have structurally normal hearts but recents studies have shown subtle structural or microscopic abnormalities especially of the right ventricle including dilation of the right ventricular outflow tract and localized inflammation.6, 7

The prevalence of BrS is not well established, but is estimated to range between 1: 2,000 and 1: 5,000 people, with a higher prevalence in South‐East Asia.8

CASE DESCRIPTION

We report a case of a 44‐year‐old male who presented to the emergency department (ED) complaining of chest pain that was sharp, retrosternal severe, and nonradiating. It started while lifting heavy boxes at work approximately 2 hours prior. The pain improved with rest but did not resolve completely.

Patient's medical history was relevant for coronary artery disease, hypertension, diabetes mellitus type 1, recurrent hospitalizations because of diabetes ketoacidosis (3 episodes in fewer than 6 months) in the setting of alcohol abuse and noncompliance with his regimen. He had an anterior ST‐elevation myocardial infarction 1 year earlier and underwent cardiac catheterization. Findings included a 70% stenosis of left anterior descendant (LAD) artery as well distal apical LAD occlusion treated medically.

Family history was significant for sudden infant death syndrome (SIDS), son who died at age of 5 months.

Upon arrival to the ED his vital signs were within normal limits with the exception of a heart rate of 155 bpm. Initial electrocardiogram (EKG) showed sinus tachycardia at a rate of 151, with “coved” ST elevations in leads V₁ and V₃ and “saddle back” ST elevation in lead V₂ (Fig. 1.)

Figure 1.

Brugada pattern with saddle back appearance.

The first set of cardiac biomarkers revealed a troponin I of 0.02 ng/mL. At 6 and 12 hours peaked and plateau at 0.05 ng/mL. Initial lab work was also relevant for severe hyperkalemia (7.4 mmol/L), hyperglycemia (501 mg/dL), ketonuria, metabolic acidosis (HCO3 6 mmol/L) with high anion gap (34 mmol/L).

Patient was started on aspirin 324 mg, sublingual nitroglycerin and intravenous metoprolol with complete resolution of his chest pain within 30 minutes.

A second EKG done 1 hour after his arrival, obtained while chest pain free, showed “coved” ST elevation in leads V₁ through V₃ but the previous “saddle back” ST elevations were no longer present (Fig. 2).

Figure 2.

Brugada pattern Type 1.

Echocardiogram done at bed side disclosed a normal left ventricular systolic function with no wall motion abnormalities.

Metabolic abnormalities were addressed with aggressive fluid resuscitation, intravenous calcium gluconate and sodium bicarbonate as well as an insulin drip. After resolution of his hyperkalemia and metabolic acidosis, his EKG returned to normal (Fig. 3). Urine culture grew E.coli multisensitive, treated with ceftriaxone.

Figure 3.

ECG with resolution of Brugada pattern.

DISCUSSION

We described a case of a patient with a family history relevant for SIDS in one of his children who presented to the ER several times in the past with typical Type 1 EKG pattern for BrS in the setting of DKA with severe hyperkalemia followed by complete resolution after electrolyte normalization.

Many clinical situations have been reported to exacerbate the EKG pattern of BrS, including fever, hyperkalemia, hypokalemia, hypercalcemia, alcohol or cocaine intoxication, the use of certain medications, such as channel blockers, tricyclic or tetracyclic antidepressants, vagotonic agents, alpha‐adrenergic agonists, and beta‐adrenergic blockers.9 In our case, the unmasked EKG patterns were always evident in setting of DKA and severe hyperkalemia which promptly resolved after adequate treatment.

Three EKG patterns have been described in BrS: Type 1 is,10 characterized by a coved ST‐segment elevation ≥2 mm followed by a negative T wave. The type 2 ST‐segment elevations has a saddle back appearance with a high takeoff ST‐segment elevation of ≥2 mm, a trough displaying ≥1 mm ST elevation, and then either a positive or biphasic T wave. Type 3 has either a saddle back or coved appearance with an ST‐segment elevation of <1 mm.10 Type 2 and type 3 EKG are not diagnostic of BrS.

Our patient presented not only with type 1 EKG pattern but type 2 ST‐elevation was also noted especially in the initial EKG. BrS is diagnosed when a type 1 ST‐segment elevation is observed in more than one right precordial lead (V₁–V₃), in conjunction with one of the following: Documented ventricular fibrillation (VF), polymorphic ventricular tachycardia (VT), a family history of SCD at less than 45‐year old, coved‐type EKGs in family members, inducability of VT with programmed electrical stimulation, syncope, or nocturnal agonal respiration.10

Our patient did not report a history of syncopal events or a family history of SCD except for a relevant history of SIDS in one of his children for this reason; he does not meet the current criteria to be diagnosed with BrS, unless SIDS is included in the definition. The link between SIDS and SCD is poor, however, several studies have concluded there may be a genetic predisposition to SIDS resulting from mutations in cardiac ion channel‐related genes.

Moreover, in BrS patients, sudden death often occurs at rest or while sleeping, which makes BrS a likely cause for SIDS.11, 12 Interestingly, some ion channel‐related mutations are detected in a minority of BrS patients, and if such mutations are found, it is almost always a mutation in SCN5A, which is the gene that encodes for the α subunit of the cardiac sodium channel gene. All of these findings raise suspicion there could be an important genetic link among SIDS, SDC, and BrS.

SCN5A mutations account for 18%–30% of BrS cases and more than 80 mutations in SCN5A have been linked to the syndrome since 2001.9, 10

It is crucial to determine whether a patient is symptomatic or asymptomatic when the diagnosis of BrS is made since this could guide physicians performing a risk stratification strategy. Patients with a history of syncope (noncardiac excluded) and a history of cardiac arrhythmias in patients with type 1 EKG Brugada pattern have an increase risk for SCD when compared with patients without syncope and spontaneous EKG pattern. So far the only intervention with proven efficacy in preventing sudden death is an implantable cardioverter desfibrillator (ICD), therefore risk stratification is vital to identify patients at risk of SCD.

Currently, the role of EP testing as well as a pertinent family history of SCD in risk stratification remains controversial especially in asymptomatic patients however there is some evidence13 male sex and a family history of SCD should be considered risk factors for subsequent SCD when risk stratifying this population.

Current guidelines from the second consensus conference,10 reported that for symptomatic patients with type 1 Brugada EKG (either spontaneous or inducible with sodium channel blockade) should receive an ICD without need for EPS study whereas asymptomatic patients displaying a type 1 Brugada EKG should undergo EPS if a family history of SCD is suspected. Asymptomatic patients with inducible type 1 EKG and without family history should be followed closely.10

The 2006 ACC/AHA/ESC guidelines for ventricular arrhythmias did not consider a family history of SCD as a risk factor and we should not make any assumption that asymptomatic individuals with the characteristic EKG but without family history were at low risk for fatal arrhythmias neither family members of an individual with SCD were at increased risk.

They concluded that EP testing may be considered for risk stratification in asymptomatic BrS patients with spontaneous ST elevation with or without a mutation in the SCN5A gene.14, 15

CONCLUSIONS

Risk stratification for SCD is clinically important because implantation of an ICD is the only intervention able to prevent SCD. Currently, the clinical approach for asymptomatic patients that exhibit EKG pattern of BrS remains controversial and there are a significant number of patients who may present a diagnostic EKG pattern but do not meet the current criteria for diagnosis of BrS. To include SIDS as part of the diagnostic criteria for BrS could be extremely relevant since it would help identifying, risk stratifying and monitoring a significant number of families susceptible to develop SCD (as well as SIDS).