Several factors can precipitate Brugada syndrome on ECG.1-3,6,10 A study of fever in patients with a genetic mutation for Brugada syndrome found a greater loss of function of the sodium channel current at higher temperatures.6,10 Adler and colleagues also found that febrile patients seen in the ED over a 32-month period were 20 times more likely to have the type 1 pattern.10 Consumption of a large meal, cocaine, and alcohol toxicity are vagatonic and have been known to trigger a Brugada ECG.4,7,10
To arrive at the diagnosis of Brugada syndrome, several benign and pathophysiologic conditions that cause ST-segment elevation in the right precordial leads must be ruled out.3,7 Known causes of this characteristic change in ECG morphology include myocardial ischemia or infarction, electrolyte imbalance (hyperkalemia, hypokalemia, hypercalcemia), early repolarization syndrome as seen in young athletes, arrhythmogenic right ventricular dysplasia/cardiomyopathy, Prinzmetal angina, left ventricular hypertrophy, pulmonary embolism, Duchenne muscular dystrophy, compression of the right ventricular outflow tract via tumor or hemopericardium, pectus excavatum, dissecting aortic aneurysm, and atypical left bundle-branch block.3,4 Echocardiography, stress echocardiography, and cardiac MRI can be used to exclude structural cardiac defects.
Patients with Brugada syndrome who are at highest risk for sudden cardiac arrest have a type 1 pattern with a history of VF, VT, or syncopal episode. Programmed electrical stimulation during a standard electrophysiology study can be used as a tool in risk stratification. However, although initial research by the Brugada brothers determined the inducibility of ventricular dysrhythmia during programmed electrical stimulation to be an important predictor of dysrhythmic events, two major studies have challenged this theory: the FINGER and PRELUDE studies.
The FINGER study was the largest trial conducted to identify prognosis of Brugada syndrome and risk factors for sudden cardiac death.11 Eleven centers in France, Italy, the Netherlands, and Germany enrolled 1,029 patients with type 1 Brugada syndrome occurring spontaneously or following a drug infusion challenge. Patients were grouped into cohorts according to presentation: aborted sudden cardiac arrest, syncope, or asymptomatic. All patients underwent a uniform protocol at programmed electrical stimulation.
In the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) Registry, Priori and colleagues assessed the predictability of inducible VF or VT at programmed electrical stimulation for future dysrhythmic events in patients with no history of sustained VF or VT.12 The study enrolled 308 patients with type 1 Brugada syndrome on ECG and no history of prior sudden cardiac death; patients received uniform programmed electrical stimulation. In a follow-up period of 36 months, inducibility of VF or VT at programmed electrical stimulation did not correlate with an increased risk of future dysrhythmic events. Programmed electrical stimulation thereby was not found to be a useful tool in identifying high-risk patients with Brugada syndrome.7 A multicenter trial by Sacher and colleagues followed 378 patients with Brugada syndrome who received implantable cardioverter defibrillators: 31 for aborted sudden cardiac arrest, 181 for syncope, and 166 who were asymptomatic.13 At 10 years, the device recognized and appropriately treated ventricular dysrhythmias in 48% of the sudden cardiac arrest group, 19% for those with syncope, and 12% for asymptomatic patients. In asymptomatic patients, the devices appropriately recognized and treated ventricular dysrhythmia at a rate of 1% per year.13 The risk of sudden cardiac arrest in asymptomatic patients with Brugada syndrome due to new-onset VF is low.4,14
PROGNOSIS AND TREATMENT
Research by Postema and colleagues on drug safety in patients with Brugada syndrome led to the establishment of four categories of medications accepted by the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC): Drugs to be avoided, drugs to be preferably avoided, antiarrhythmic drugs, and diagnostic drugs (Table 2).15 All patients with Brugada syndrome, regardless of the degree of symptoms, should be thoroughly counseled to avoid medications that are known to induce the type 1 pattern and ventricular dysrhythmias.7,15 Among the many categories of drugs that should be avoided when a patient carries this diagnosis are antiarrhythmics, particularly class Ia/Ic, tricyclic antidepressants, and psychotropic drugs, common anesthetics such as propofol and bupivacaine, and a number of antianginal medications. Patients should avoid ventricular dysrhythmia triggers (cocaine, alcohol toxicity, and electrolyte imbalances). Since fever can be a trigger, it should be aggressively treated with antipyretics.
Patients who survive sudden cardiac arrest due to an irreversible cause should receive an ICD for secondary prevention.5,7,16 In patients with documented VT, documented self-terminating VT, or those with spontaneous ST-segment elevation and syncope, an ICD is considered reasonable.17
Drug therapy to prevent ventricular dysrhythmias in patients with Brugada syndrome is not the standard of care, as no trials have proven its efficacy.8 According to the 2006 ACC/AHA/ESC guidelines, however, an IV infusion of the beta-adrenergic agonist isoproterenol can be used to treat dysrhythmic or electrical storm. Quinidine, a class Ia antiarrhythmic, is being investigated as a potential treatment for patients with recurring VT. Quinidine reduces the risk of ventricular dysrhythmias by decreasing potassium outflow, making right ventricular outflow tract action more consistent.3,13,15 A study by Belhassen and Viskin demonstrated quinidine's prospective effectiveness by studying 25 patients with Brugada syndrome (15 symptomatic and 10 asymptomatic).18 All patients underwent programmed electrical stimulation, were inducible for ventricular dysrhythmia at baseline, and were treated with quinidine. In follow-up programmed electrical stimulation testing on quinidine, 22 of the 25 patients were noninducible.18
Treatment in the asymptomatic patients with Brugada syndrome is highly controversial.3,5,16 Although inducibility of VT or VF at programmed electrical stimulation was initially thought to be a predictor of future arrhythmic events by Brugada and colleagues, the FINGER study, the largest study of patients with Brugada syndrome thus far, disproved this theory.13 Programmed electrical stimulation in asymptomatic patients remains a topic of debate.
Brugada syndrome, an inherited arrhythmogenic disease transmitted in an autosomal dominant fashion, is associated with increased risk of sudden cardiac arrest due to ventricular dysrhythmias. Syncope, polymorphic VT, VF, or sudden cardiac death may be the initial presenting signs, and occur most often in men in their 40s. Proper identification and workup for the characteristic ST-segment elevation in the right precordial leads V1 to V3 on ECG can be potentially lifesaving. A type 1 or coved ST-segment elevation is a diagnostic pattern; a type 2 or downsloping pattern may require an IV drug challenge to reveal a concealed type 1 pattern. Ventricular dysrhythmias, syncope, and sudden cardiac death are poor prognostic factors. Patients may need an ICD for primary or secondary prevention of sudden cardiac arrest. Asymptomatic patients have decreased incidence of dysrhythmia, and often require close follow-up and monitoring. New guidelines suggest that patients with Brugada syndrome be treated at an experienced center.4
1. Antzelevitch C, Brugada P, Borggrefe M, et al Brugada syndrome
: report of the Second Consensus Conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation
2. Wilde AA, Antzelevitch C, Borggrefe M, et al Proposed diagnostic criteria for the Brugada syndrome
: consensus report. Circulation
3. Antzelevitch C. Brugada syndrome
. Pacing Clin Electrophysiol
4. Priori SG, Wilde AA, Horie M, et al HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm
5. Mizusawa Y, Wilde AA. Brugada syndrome
. Circ Arrhythm Electrophysiol
6. Kusano K. Brugada syndrome
: recent understanding of pathophysiological mechanism and treatment. J Arrhythmia
7. Wylie JV, Garlitski AC. Brugada syndrome
. UpToDate. http://http://www.uptodate.com
/contents/brugada-syndrome?detectedLanguage=en&source=search_result&search=brugada+syndrome&selectedTitle=1%7E50&provider=noProvider. Accessed March 2, 2015.
8. Brugada R, Campuzano O, Brugada P, et al Brugada syndrome
. In: Pagon RA, Adam MP, Bird TD, et al., eds. GeneReviews
. Seattle, WA: University of Washington; 1993–2013. http://http://www.ncbi.nlm.nih.gov
/books/NBK1517. Accessed March 2, 2015.
9. Baranchuk A, Gottshalk B, Anselm DD. Brugada phenocopy: update 2014. Proceedings of the 41st International Congress on Electrocardiology. Bratislava, Slovakia, June 2014.
10. Adler A, Topaz G, Heller K, et al Fever-induced Brugada pattern: how common is it and what does it mean. Heart Rhythm
11. Probst V, Veltmann C, Eckardt L, et al Long-term prognosis of patients diagnosed with Brugada syndrome
: results from the FINGER Brugada Syndrome
12. Priori SG, Gasparini M, Napolitano C. Risk stratification in Brugada syndrome
: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol
13. Sacher F, Probst V, Maury P, et al Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome
: a multicenter study-part 2. Circulation
14. Tagaki M. Risk stratification in Brugada syndrome
: role of programmed electrical stimulation. J Clinic Experiment Cardiol
. 2013;S10:004. http://omicsonline.org/risk-stratification-in-brugada-syndrome-role-of-programmed-electrical-stimulation-2155-9880.S10-004.php?aid=12668. Accessed March 31, 2015.
15. Postema PG, Wolpert C, Amin AS, et al Drugs and Brugada syndrome
patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org
). Heart Rhythm
16. Shimizu A. Indication of ICD in Brugada syndrome
. J Arrhythmia
17. Epstein AE, DiMarco JP, Ellenbogen KA, et al ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol
18. Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome
Keywords:Copyright © 2015 American Academy of Physician Assistants
Brugada syndrome; ECG; sudden cardiac arrest; ST-segment elevation; polymorphic ventricular tachycardia; ventricular fibrillation