When should I suspect Brugada syndrome in an adolescent?

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Elsevier ClinicalKey Clinical Overview

Diagnosis Subsubsection Title: Age: Age of onset of symptoms is typically around 40 years ( youngest reported is age 2 days and oldest is 84 years Mean age for occurrence of cardiac events is 42 ± 15 years Patient may report family history of Brugada type 1 ECG or sudden cardiac death (especially when occurring in those younger than 45 years) In appropriate populations, cases of sudden infant death syndrome may rarely be associated with Brugada syndrome Subsubsection Title: Sex: 8 to 10 times more prevalent in males than in females Men with Brugada syndrome are at higher risk for arrhythmic events and sudden death than women with Brugada syndrome Men present more frequently with symptoms (syncope in 18%, aborted sudden death in 6%) than women (syncope in 14%, aborted sudden death in 1%) Testosterone is believed to contribute to development of Brugada syndrome Limited data for Brugada syndrome shows no difference between phenotypic expression in boys and girls younger than 16 years of age Subsubsection Title: Genetics: Brugada syndrome is related to mutations in 1 or more of the 16 identified genes that code for myocardial ion channels (sodium, potassium, and calcium) that are involved in development of myocardial action potentials Autosomal dominant pattern of transmission Incomplete, variable penetrance Approximately 350 mutations are associated with Brugada syndrome Significant phenotypic variability is encountered Most commonly involved gene and the first described in Brugada syndrome is SCN5A , which codes for the α subunit of the cardiac sodium channel (OMIM *600163) 15% to 30% of patients with Brugada syndrome possess this causative genetic mutation In addition to sodium channels, potassium channels may be affected as first determined for the KCNE3 gene (OMIM *604433)

Diagnosis Family history of Brugada type 1 ECG or sudden cardiac death (especially when occurring at less than 45 years of age) may be obtained; includes sudden infant death syndrome (rarely associated with Brugada syndrome) Patients are typically asymptomatic; however, symptoms may be reported, usually beginning in the fourth decade of life Symptoms related to arrhythmias typically occur at rest, during nighttime or sleep, and suggest that vagal activity may contribute to their development Rarely do symptoms occur during exercise Syncope (cardiogenic) Occurs in 17% to 42% of diagnosed patients Neurally mediated syncope has also been reported (caused by dysregulation of autonomic tone) Witnessed nocturnal agonal respiration (attributed to self-terminating ventricular arrhythmia) Chest discomfort Dizziness Palpitations Supraventricular arrhythmias occur in approximately 20% of patients and can be responsible for palpitations and/or dizziness

Terminology Brugada syndrome is a genetically determined, primary electrical cardiac syndrome characterized on ECG as an atypical right bundle branch block pattern with persistent ST-segment elevation in the right precordial leads Occurs in structurally normal hearts and is associated with syncope or sudden cardiac death caused by polymorphic ventricular tachycardia or ventricular fibrillation Diagnostic criteria are based on the Heart Rhythm Society, European Heart Rhythm Association, and Asia Pacific Heart Rhythm Society consensus statement on diagnosis and management of patients with inherited primary arrhythmia syndromes Criteria set 1 ST-segment elevation with type 1 morphology of 2 mV or greater in 1 or more right precordial leads V₁, V₂, positioned in second, third, or fourth intercostal space Occurs spontaneously or after provocative drug test with IV administration of class I antiarrhythmic drugs Criteria set 2 Type 2 or type 3 ST-segment elevation in right precordial leads V₁, V₂, positioned in second, third, or fourth intercostal space when a provocative drug test with class I antiarrhythmic drugs induces type 1 ECG morphology Brugada syndrome is definitively diagnosed when 1 of the criteria sets is accompanied by: Positive family history: sudden cardiac death in a family member younger than 45 years, or finding of ECG type 1 in a relative Symptoms related to arrhythmia: syncope, dizziness, chest discomfort, or nocturnal agonal respiration Ventricular arrhythmias: polymorphic ventricular tachycardia or ventricular fibrillation Coved-type ECGs (ST-segment elevation with downward-convex shape) in family members Inducible ventricular arrhythmias on electrophysiologic study

Synopsis Brugada syndrome is a genetically determined, primary electrical cardiac syndrome characterized on ECG as an atypical right bundle branch block pattern with persistent ST-segment elevation in the right precordial leads Brugada ECG morphology is categorized into 3 pattern subtypes, highlighted by an atypical right bundle branch block pattern with persistent ST-segment elevation in the right precordial leads Diagnosis depends on ECG findings and clinical criteria Only ECG type 1 pattern is considered diagnostic of Brugada syndrome Clinical criteria for diagnosis include presence of Brugada syndrome ECG changes, and: Sudden cardiac death in a family member younger than 45 years, finding of ECG type 1 in a relative, or Symptoms related to arrhythmia: syncope, dizziness, chest discomfort, or nocturnal agonal respiration, or Ventricular arrhythmias: polymorphic ventricular tachycardia or ventricular fibrillation If ECG findings are suspicious (ie, type 2 or 3), pharmacologic testing via sodium channel blockers is necessary to unmask condition Ajmaline is the most effective drug for this purpose, but flecainide is available in the United States Effective treatment is placement of an implantable cardioverter-defibrillator Quinidine may be used as an alternative therapy when implantable cardioverter-defibrillator is contraindicated Brugada syndrome is responsible for 4% to 12% of all sudden cardiac deaths, and most patients who recover from aborted sudden cardiac death are at risk of a new arrhythmic event

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Olgin, Jeffrey E. (2024). In Goldman-Cecil Medicine (pp. 303). DOI: 10.1016/B978-0-323-93038-3.00049-6

The baseline ECG is critical in the evaluation of a patient with palpitations or syncope. The presence of ventricular preexcitation, as manifested by a short PR interval and a delta wave (seeFig. 52-10), establishes the likely diagnosis of Wolff-Parkinson-White syndrome in a patient with palpitations and AV reciprocating tachycardia (Chapter 52); a 12-lead ECG can also be used to determine the location of the responsible accessory pathway. The baseline ECG provides useful predictive information about the likelihood of conduction system abnormalities being responsible for bradyarrhythmias (e.g., sinus bradycardia suggests sinus node dysfunction, a prolonged PR interval suggests AV nodal disease, and a widened QRS suggests disease below the AV node). The ECG is also useful in diagnosing prior myocardial infarction (i.e., pathologic Q waves), which raises the likelihood of ventricular tachycardia as a potential cause of syncope or palpitations. Abnormalities such as a prolonged QT interval in a patient with syncope and a family history of syncope or sudden death suggest one of the congenital long QT syndromes (Chapter 50). An incomplete right bundle branch block with coved ST segment elevation in ECG lead V1or V2in a patient with syncope or palpitations suggests Brugada syndrome, whereas an epsilon wave, incomplete right bundle branch block, and inverted T waves in V1are suggestive of right ventricular dysplasia (Chapter 47). All these syndromes carry an increased risk for recurrent syncope and sudden death if untreated (Chapters 50and53). The short QT syndrome (QTc ≤330 msec or QTc ≤360 plus a family history of sudden death) also predisposes to ventricular arrhythmias. Since some of these ECG findings (especially those suggestive of Brugada syndrome and even long QT syndrome) may be transient or episodic, lack of these findings does not exclude these syndromes in patients with syncope and a strong family history.

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Calkins, Hugh, Everett, Thomas H., Chen, Peng-Sheng (2022). In Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine (pp. 1387). DOI: 10.1016/B978-0-323-72219-3.00071-2

The 12-lead ECG is another important component in the workup of a patient with syncope (seeChapter 14). The 2017 ACC/AHA/HRS syncope guidelines provide a class I (LOE B-NR) recommendation for performing an ECG in patients with syncope.The initial ECG results in establishment of a diagnosis in approximately 5% of patients and suggests a diagnosis in another 5% of patients. Specific findings that can identify the probable cause of the syncope include QT prolongation (long-QT syndrome), the presence of a short PR interval and a delta wave (Wolff-Parkinson-White syndrome), the presence of a right bundle branch block pattern with ST-segment elevation (Brugada syndrome), or evidence of acute myocardial infarction, high-grade AV block, or T wave inversion in the right precordial leads (arrhythmogenic right ventricular dysplasia) (seeChapters 63, 65 and 67Chapter 63Chapter 65Chapter 67). Any abnormal finding on the baseline ECG is an independent predictor of cardiac syncope or increased mortality and suggests the need to pursue evaluation of cardiac causes of syncope.Most patients with syncope have normal findings on ECGs, which is useful because it suggests a low likelihood of a cardiac cause of the syncope and is associated with an excellent prognosis, particularly when observed in a young patient with syncope. Despite the low diagnostic yield of electrocardiography, the test is inexpensive and risk free and is considered a standard part of the evaluation of virtually all patients with syncope.

4.

Minier M, Probst V, Berthome P, et al. Heart Rhythm. 2020;17(5 Pt A):743-749. doi:10.1016/j.hrthm.2019.11.027.

Publish date: May 5, 2020.

BACKGROUND: Despite a strong genetic background, Brugada syndrome (BrS) mainly affects middle-age patients. Data are scarce in the youngest and oldest age groups. OBJECTIVE: The purpose of this study was to describe the clinical characteristics and variations in rhythmic risk in BrS patients according to age. METHODS: Consecutive BrS patients diagnosed in 15 French tertiary centers in France were enrolled from 1993 to 2016 and followed up prospectively. All of the clinical and ECG data were double reviewed. RESULTS: Among the 1613 patients enrolled (age 45 ± 15 years; 69% male), 3 groups were defined according to age (52 patients <17 years; 1285 between 17 and 59 years; and 276 >60 years). In the youngest patients, we identified more female gender (42%), diagnosis by familial screening (63%), previous sudden cardiac death (15%), SCN5A mutation (62%) sinus dysfunction (8%) and aVR sign (37%) (P <.001). The oldest patients had the same clinical characteristics except for gender (40% women; P <.001). During median follow-up of 5.5 [2.1, 10.0] years, 91 patients experienced an arrhythmic event, including 7 (13%) in the youngest patients, 80 (6%) in middle-age patients, and 4 (1%) in the oldest patients. Annual event rates were 2.1%, 1%, and 0.3%, respectively (P <.01). CONCLUSION: Age on diagnosis changes the clinical presentation of BrS. Although children are identified more during familial screening, they present the highest risk of sudden cardiac death, which is an argument for early and extensive familial screening.