Brugada Syndrome

Sudden Thump
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Diagnosis and reasoning

This patient has experienced an episode of rapid but regular palpitations, which suggests either sinus tachycardia, supraventricular tachycardia (SVT) or ventricular tachycardia (VT). The faintishness and feeling of impending doom suggests hemodynamic compromise. While this favors VT, it should be kept in mind that SVT of a sufficiently high rate may cause cardiac decompensation. Further differentiation is best performed by evaluating the ECG obtained during the episode of palpitations. His ECG shows a broad complex tachycardia, limiting the possibilities to VT; SVT with a bundle branch block; or SVT via an accessory pathway with antidromic conduction. ECG features of use in differentiating VT from SVT include: 1. AV disassociation (i.e. independent atrial and ventricular rhythms) 2. Capture beats (where a normal sinus beat transiently "captures" the ventricles, resulting in a normal QRS complex) 3. Fusion beats (where both the sinus beat and ventricular foci simultaneously stimulate the ventricles, resulting in a QRS complex which is midway between the VT beats and normal QRS complexes) 4. Positive or negative concordance (when all the QRS complexes in the chest leads are either predominantly positive or predominantly negative) This patient's ECG shows fusion and capture beats, which is sufficient to establish the rhythm abnormality to be VT. While a variety of diseases may give rise to VT, an acute coronary syndrome should be excluded first. Other important etiologies include structural cardiac disease, electrolyte and metabolic abnormalities and drugs. Conduction defects are also a possibility. His history is not suggestive of an acute coronary syndrome, while examination reveals no signs suggestive of congenital or valvular cardiac disease. Examination of his resting ECG shows downsloping ST-segment elevations and T-inversions in the leads V1 to V3, which at first glance suggests a ST elevation myocardial infarction (STEMI). However, closer examination shows these to be more in line with the changes found in Brugada syndrome, which is well known to cause VT. Note that although cardiac enzyme levels are elevated, this is of little diagnostic value, as it might simply be a sequelae of cardioversion. Echocardiography shows a normal appearing heart. Note that the cardiac defects most likely to give rise to VT are hypertrophic cardiomyopathy and right ventricular arrhythmogenic cardiomyopathy. Thus, the diagnosis is indeed Brugada syndrome. An implantable cardioverter defibrillator (ICD) is the only management option which alters the course of Brugada syndrome. Antiarrhythmic therapy is of little or no benefit.


Discussion

Brugada Syndrome is characterized by the triad of "coved" ST-segment elevations in the ECG, a high incidence of lethal ventricular arrhythmias, and an apparently structurally normal heart. The incidence is estimated at between 5 to 14 per 1,000 individuals, with those of eastern asian descent affected more often. Inheritance occurs as an autosomal dominant trait, although the disease may be sporadic in up to 60% of patients. Several different genetic defects may give rise to Brugada Syndrome. These include mutations in the SCN5A or GPD-1L genes, leading to loss of function in the sodium channels of the cardiac myocytes; and mutations in the CACNA1c or CACNB2b genes, leading to loss of function of the cardiac calcium channels. Patients with Brugada syndrome may present with palpitations, syncope or even cardiac arrest (terminating in sudden cardiac death). Most often, these are secondary to ventricular arrhythmias such as polymorphic ventricular tachycardia or ventricular fibrillation (VF). Supra-ventricular arrhythmias such as atrial fibrillation have also been observed in a significant proportion of patients. Typically, ventricular arrhythmias and sudden cardiac death occur at rest, especially during nighttime or sleep. While men and women would be expected to inherit the defective gene equally, it is a surprising fact that the disease manifests 8 to 10 times more often in males. This is postulated to be due to sex-related intrinsic differences in ionic currents and the influence of male hormones. In addition, most patients present in or around the fourth decade of life. The reason for this is unknown. The diagnosis of Brugada syndrome requires the appearance of "coved type" ST-segment elevations >= 2mm in more than one right precordial lead (i.e. V1 to V3), either spontaneously or following exposure to sodium channel blocking drugs, AND either a documented ventricular arrhythmia, a family history of the disease or a history of arrhythmia related symptoms. Note also that other conditions capable of causing similar ECG changes should be ruled out. The most important of these are hypertrophic cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy, drugs and electrolyte abnormalities. ICD placement is the only measure proven to affect the course of Brugada syndrome. The current consensus is that symptomatic patients should always receive an ICD. The decision in asymptomatic patients is considerably trickier. These patients should undergo electrophysiological studies (EPS) for risk stratification - and those with inducible VF and a typical ECG at baseline, or with a sodium blocker induced ECG and a positive family history of sudden cardiac death (SCD) should also undergo ICD implantation. Asymptomatic patients who only develop ECG changes after sodium blockage, and who have no family history of SCD should only be closely followed up. Given that ICD implantation is a non-trivial, expensive procedure, there have been considerable interest in developing a pharmacological approach to management. Quinidine, a class I anti-arrhythmic agent has been assessed in several clinical studies and been proven as a good adjunctive therapy in patients with ICDs. Beta-adrenergic agents and dimethyl lithospermate B are other drugs which are undergoing investigation. As Brugada syndrome is hereditary, family members of patients should be screened appropriately.


Take home messages

  1. The main causes of a broad complex tachycardia are VT, SVT with a bundle branch block, and SVT via an accessory pathway with antidromic conduction.
  2. The main ECG features of use in differentiating VT from an SVT are AV disassociation, capture beats and fusion beats, and positive or negative concordance.
  3. Brugada Syndrome is characterized by the triad of coved ST-segment elevations in the ECG, a high incidence of lethal ventricular arrhythmias, and an apparently structurally normal heart.
  4. ICD placement is the only measure proven to affect the course of Brugada syndrome.

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  1. American Journal of Cardiology : Approach to the Diagnosis and Initial Management of the Stable Adult Patient With a Wide Complex Tachycardia (2008)
  2. American Journal of Emergency Medicine : Wide Complex QRS Tachycardia - ECG Differential Diagnosis (1998)
  3. ESC : Management of patients with palpitations: a position paper from the European Heart Rhythm Association (2011)
  4. Hellenic Journal of Cardiology : Brugada Syndrome: Update 2009 (2009)
  5. Indian Pacing and Electrophysiology Journal : A Review of the Mechanisms of Ventricular Arrhythmia in Brugada Syndrome (2010)
  6. NEJM : ST-Segment Elevation in Conditions Other Than Acute Myocardial Infarction (2003)