Case 3: A 45-Year-Old Man with Chest Pain After an Automobile Accident

You are asked to see a 45-year-old man with no significant past medical history in the Emergency Department following a motor vehicle collision. He was slowing to a stop in a sedan when his car was hit from behind by a semi-trailer truck traveling 40 mi/h. He was wearing a seat belt and the airbag did not deploy. He denies any head trauma or loss of consciousness surrounding the event. He was able to get out of his car unassisted, and shortly thereafter developed constant, deep, substernal chest pain that he described as dull and 5 out of 10 in severity. He has no other associated symptoms such as shortness of breath, diaphoresis, nausea, or vomiting. The automated 12-lead electrocardiogram () interpretation is read as "ACUTE MI."

What is your interpretation of this ECG (Figure 3.1)?

Figure 3.1 ECG at the time of presentation.

Brugada Syndrome

This patient has Brugada pattern on his ECG which is described as a right bundle branch block (), normal QT internal, and persistent ST-segment elevation in leads V1 to V2-V3 that is not explainable by electrolyte derangements, ischemia, or structural heart disease (Brugada and Brugada 1992). According to the 2013 consensus statement on inherited arrhythmias, this pattern is definitively diagnosed when Brugada type 1 ST-segment elevation is observed either spontaneously or after administration of intravenous sodium channel-blocking agent in at least one precordial lead (V1 and V2) (Priori et al. 2013).

Clinical manifestations vary, and in the case of isolated Brugada pattern on ECG such as in this case, the patient may be asymptomatic. A patient who presents with the Brugada ECG criteria but without the clinical characteristics is said to have the Brugada pattern but not the syndrome. Diagnosis of Brugada Syndrome depends on both characteristic ECG findings (either spontaneous or inducible) and appropriate clinical findings (unexplained syncope, self-terminating polymorphic ventricular tachycardia, documented ventricular fibrillation, family history of sudden cardiac death at less than 45 years of age, Brugada ECG pattern in a family member, and/or inducibility of ventricular tachycardia by electrophysiologic study). The syndrome usually manifests during adulthood with a mean age of sudden death of 41 years. Other common symptoms include ventricular fibrillation or aborted sudden cardiac death, syncope, nocturnal agonal respiration, palpitations, or chest discomfort. These symptoms most frequently occur during rest or sleep, during a febrile state, or with vagotonic conditions. Rarely do symptoms manifest with exercise (Priori et al. 2013). The syndrome appears to be more common in persons of Asian descent (Alings and Wilde 1999), and men are 8-10 times more likely to be affected (Priori et al. 2013). These patients are at an increased risk of ventricular tachyarrhythmias and sudden cardiac death (Priori et al. 2013).

In this case, Brugada Syndrome was unrelated to the motor vehicle accident (the patient had no palpitations or loss of consciousness and the accident was not attributable to his error). Recognition of this pattern on ECG is very important however for at least two reasons: (i) interpretation of the ST elevation as an acute injury pattern would result in the faulty diagnosis of acute myocardial infarction or cardiac contusion; and (ii) individuals with Brugada Syndrome are at risk of sudden cardiac death and this patient should be further evaluated to see if he would benefit from primary prevention.

The Brugada Syndrome was initially described in 1992 by Brugada and Brugada who reported eight patients with a history of cardiac arrest and ECG findings of RBBB and ST-segment elevation in the right precordial leads and no evidence of any structural heart disease. Prior to that, the Centers for Disease Control and Prevention had reported cases of sudden death in young immigrants from Southeast Asia, described as Sudden Unexplained Death Syndrome () which has subsequently been shown to be closely related to, if not the same as, the Brugada syndrome.

The Brugada Syndrome is an autosomal dominant genetic disorder with variable penetrance characterized by abnormal electrophysiologic activity in the right ventricular epicardium. Approximately one-fourth of cases are caused by loss of function mutations in the cardiac sodium channel SCN5A (abnormalities in this gene have also been linked to Long QT Syndrome 3). This gene encodes the a-subunit of the sodium ion channel and, when abnormal, results in increased inactivation of the sodium channel with a prolonged recovery time.

Three ECG patterns have been described in the Brugada Syndrome, with all three types having in common ST elevation (=2 mm at the J point) in the right precordial leads. In the "classic" Brugada ECG (type 1) the ST segment is continuously downsloping from the top of the R wave, is not elevated above baseline at the terminal portion and ends with an inverted T wave (such as in this patient). Types 2 and 3 have a "saddle-back" ST-T wave configuration (Figure 3.1). The ST segment descends toward the baseline with upward concavity and then rises again to an upright or biphasic T wave. Type 2 is defined by the terminal portion of the ST segment being elevated =1 mm whereas in type 3 the terminal portion of the ST segment is elevated <1 mm. The ECG changes can be dynamic, with the same patient manifesting all three types at various points in time.

In some patients, complete or incomplete RBBB is present. In others, high take-off ST-segment elevation (accentuated J-point elevation) in the right precordial leads mimics the pattern of RBBB, but wide S waves in leads I, aVL, V5, and V6 typically seen in RBBB are absent (such as in this case). In these cases, the R in V1 is thought to be due to early repolarization of the right ventricular epicardium rather than a RBBB.

The Brugada pattern on ECG can be either persistent or inducible. Medications (including sodium channel blockers, cocaine, antidepressants, and antihistamines), electrolyte abnormalities, and acute illnesses may elicit ST-segment elevation in leads V1 to V3 in susceptible patients. To aide in the diagnosis, provocation testing by infusion of selected class IC antiarrhythmic drugs (e.g. flecainide or procainamide) can unmask the Brugada ECG pattern in affected subjects.

It is important to risk stratify patients based on clinical characteristics, as high-risk patients benefit from (implantable cardioverter defibrillator) placement. The risk of lethal or near-lethal arrhythmic episodes among previously asymptomatic patients with Brugada pattern on ECG is estimated between 1 and 8% depending on the study. Irrespective of other predictors of outcome, patients with history of ventricular fibrillation are inherently high risk (Priori et al. 2013). Additionally, patients presenting with syncopal episodes in the presence of spontaneous Brugada type I ST elevation in leads V1-V2 have high rates of cardiac events in follow-up (Priori et al., 2002). These first two patient groups have a strong indication for ICD placement. Other indicators of increased risk are the presence of fragmented QRS, a refractory period of <200 ms, and male sex (Priori et al. 2013).

At this time, the only effective strategy for prevention of sudden cardiac death in patients with Brugada Syndrome is placement of an ICD. Please see Figure 3.2 for indications for ICD placement. Lifestyle modifications are also important for survival in Brugada Syndrome. There are numerous medications that may induce or aggravate ST-segment elevation in precordial leads, and patients with Brugada Syndrome are advised to avoid these. A complete list can be found at https://www.brugadadrugs.org. Additionally, all patients should avoid excessive alcohol intake, and immediately treat fevers with antipyretic drugs (Marquez et al. 2012).

Figure 3.2 Consensus recommendations for ICD placement in patients with Brugada Syndrome.

Source: Reproduced with the permission of Priori et al. (2013).

Pharmacologic therapy focuses on inhibition of the transient outward potassium current or increasing the sodium and calcium currents. Isoproterenol increases the L-type calcium current and is useful in treatment of electrical storm in Brugada Syndrome (Priori et al. 2013). Quinidine is a class 1a antiarrhythmic drug that has been shown to prevent the induction of (ventricular fibrillation) and suppress spontaneous ventricular arrhythmias. Quinidine is used in patients with ICD who have been shocked multiple times, cases where ICD is contraindicated, and to suppress supraventricular arrhythmias (Marquez et al. 2012; Priori et al. 2013).

Catheter ablation of malignant arrhythmias is a promising future therapeutic avenue in Brugada Syndrome. Similar to pharmacologic treatment, there have been no randomized controlled trials addressing this issue, but Nademanee et al. (2011) completed a case series which showed that epicardial substrate ablation in the right...