240514 Brugada - Tuan Nghiannnnn Y1.pptx

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1. CASE PRESENTATION INTERNAL MEDICINE Resident: Pham Tuan Nghia Faculty: Nguyen Nam Duong Teaching resident: Nguyen Dinh Tung 14 May 2024

2. CHIEF COMPLAINT 46-year-old female patient diagnosed with complicated UTI , hospitalized day 2, being treated with tazocin on day 1. PMH revealed: 2 syncope episodes, 3 and 1 years ago; 1 episode of lightheadedness caused by severe palpitation a couple of months ago.

3. Present illness The patient was alert, oriented. Mild headache and muscle ache. No rhinorrhea, no cough, no sore throat, no SOB, no chest pain, no abdominal pain, no dysuria.

4. DISCUSSION What additional information would you like to obtain from her?

5. The syncope episodes characteristics History of syncope: 2 episodes, 3 years and 1 year ago Triggers: Could not recall Symptoms before fainting: Dizziness and lightheadedness Location of fainting episodes: Workplace No witnesses to fainting episodes During the syncope episodes: No convulsions, no perception of sound or image. No urinary incontinence, no sweating, anxiety. Duration of fainting episodes: Approximately 30 minutes No post-ictal phase, but she feel weak after the episodes.

6. The pre-syncope episode characteristics She experienced severe palpitation Sweating Sense of impending doom “Everything started to turn black” Loss of all the strength and had to gasp for air.

7. Past medical history Other PMH : Gastritis Asymptomatic Adenomyosis. Family history: Mother and Uncle passed away suddenly at 48 and 52 years old when sleeping, respectively. Medication: Surgical history: None Allergy history: None Social history: No drinking, no smoking. ObGyn : normal menstruation.

8. PHYSICAL EXAMINATION VS: BP: 120/72 mmHg Temp: 38.5 o C RR: 19/minute HR: 84/minute General : Alert and Oriented, no palpable lymphnodes CV: S1/S2 clear, no murmurs, rubs, or gallops Lungs : Clear To Auscultation Bilaterally, no rales/wheeze/rhonchi Abdomen : soft nontender, Bowel Sound (+), Hepatosplenomegaly(-) Extremities : No abnormal findings Skin : No abnormal findings Neuro: No abnormal findings

9. Next step? What would you do next?

10. LABORATORY TEST Hematology 2. Biochemistry 3. Urinanalysis Hematology RBC HGB HCT MCV WBC NEU PLT 3.77 T/L 106 g/L 0.327 % 86.6 fL 12.6 G/l 88.0% 154 G/L Creatinin CRP AST ALT Troponin T Na + /K + /Cl - 57 umol /L 71.9 umol /L 19 U/L 11 U/L 3 ng/L (<14) 137/ 3.26 /103 mmol/L Leucocyte Protein Nitrate albumin creatinine Culture 70 negative negative 10 4.4 Negative.

11. LABORATORY TEST Hematology 2. Biochemistry 3. Urinanalysis Hematology RBC HGB HCT MCV WBC NEU PLT 3.77 T/L 106 g/L 0.327 % 86.6 fL 12.6 G/l 88.0% 154 G/L Creatinin CRP AST ALT Troponin T Na + /K + /Cl - 57 umol /L 71.9 umol /L 19 U/L 11 U/L 3 ng/L (<14) 137/ 3.26 /103 mmol/L Leucocyte Protein Nitrate albumin creatinine Culture 70 negative negative 10 4.4 Negative.

12. Next step?

13. Next step?

14. Brugada pattern ECG - AMBOSS – ST elevation ≥ 2 mm and a negative T wave in V 1  and V 2  (red overlay). The shape of ST elevation seen in V 1  is described as “coved.” – Pseudo- RBBB : The ST changes create a pattern resembling RBBB in V 1 . Pseudo- RBBB with ST elevation in V 1 –V 3  is characteristic of Brugada pattern. To diagnose Brugada syndrome, the corresponding clinical criteria must also be met, e.g., VF, syncope, or pertinent family history.

15. ECG patterns of  Brugada syndrome in leads V1-V2 This typical  coved pattern  present in V1-V2 shows the following: At the end of QRS, an ascending and quick slope with a high take-off ≥2 mm followed by concave or rectilinear downsloping ST. There are few cases of coved pattern with a high take-off between 1 and 2 mm. There is no clear r' wave. The high take-off often does not correspond with the J point. At 40 milliseconds of high take-off, the decrease in amplitude of ST is ≤4 mm ST at high take-off N ST at 40 milliseconds N ST at 80 milliseconds. ST is followed by negative and symmetric T wave. The duration of QRS is longer than in  RBBB , and there is a mismatch between V1 and V6. (B) This typical  saddle-back pattern  present in V1-V2 shows the following: High take-off of r' (that often does not coincide with J point) ≥2 mm. Descending arm of r' coincides with beginning of ST (often is not well seen). Minimum ST ascent ≥0.5 mm. ST is followed by positive T wave in V2 (T peak N ST minimum N 0) and of variable morphology in V1. The characteristics of triangle formed by r' allow to define different criteria useful for diagnosis. β angle. Duration of the base of the triangle of r' at 5 mm from the high take-off greater than 3.5 mm. Brugada syndrome: Clinical presentation, diagnosis, and evaluation – UpToDate Management of patients with a Brugada ECG pattern ( escardio.org ) coved pattern   saddle-back pattern  

16. BRUGADA PATTERN VERSUS SYNDROME? Brugada pattern : typical ECG features AND asymptomatic + have no other clinical criteria Brugada syndrome: typical ECG features AND experience of  sudden cardiac death   +   one or more of the other associated clinical criteria . What are they?

17. Associated clinical criteria Sudden cardiac arrest resulting from ventricular tachyarrhythmia Sudden unexpected noctural death syndrome More common at night occur more commonly during sleep are not usually secondary to exercise Syncope  ventricular arrhythmia or nonarrhythmic causes ( eg , neurocardiogenic) Palpitations atrial fibrillation

18. ONE LINER CHALLENGE Can you summarize the problems of this patient in one sentence?

19. One-liner 46-year-old female patient with a PMH of unknown-cause syncope, f amily history of  sudden death, presents with Brugada pattern in V1 and V2, which suggests Brugada syndrome. Horizontal Nystagmus

20. Management? What is the next step in management? Horizontal Nystagmus

21. ACUTE TREATMENT Inform relatives of the sudden cardiac death event, especially when the patient in fever episode. Manage fever Avoiding specific medications (Class I antiarrhythmic drugs; psychotropic drugs – Tricyclic antidepressants, lithium, and oxcarbazepine; anesthesia medications – Procaine, bupivacaine and prolonged propofol infusion ) Correct metabolite disbalance Testing for underlying heart disease (echo, cardiac stress testing, MRI)

22. Manage fever? Why? Brugada pattern is more common in patients with fever  – In a study of 402  febrile  emergency department patients and 909 controls, type I Brugada pattern  ECG  changes were 20 times more common in  febrile  patients (2 versus 0.1 percent. Reassuringly, none of these patients had cardiac events over 30 months of follow-up. Sudden cardiac arrest in febrile patients with  Brugada syndrome  –   In a single-center retrospective review of 111 patients with confirmed  Brugada syndrome , 22 patients had  cardiac arrest , of whom four (18 percent) had a preceding  fever . In a subset of 24 of the 111 patients with  ECGs  recorded during  fever  and  normothermia ,  ECGs  taken during  fever  had prolonged  QRS  and  QT intervals  and worsening  ST elevation

23. FOLLOW-UP TREATMENT PLAN Would you recommend implantable cardiac defibrillator for this patient? Implantable cardioverter-defibrillators ( ICDs ) - Mayo Clinic

24. RISK ASSESSMENT FOR ARRHYTHMIA OR SUDDEN CARDIAC ARREST High-risk symptoms : Brugada pattern + Sudden cardiac arrest, Syncope  (unexplained  syncope  suggestive of a tachyarrhythmia), Sustained ventricular tachycardia, Nocturnal  agonal respiration Intermediate-risk factors : Syncope that may be nonarrhythmic in origin  Family history of  SCA  and/or  Brugada Syndrome Drug-induced type 1 ECG pattern Atrial fibrillation (AF) Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate

25. Implantable cardioverter defibrillator (ICD) Consensus recommendations for implantable cardioverter-defibrillators (ICDs) in patients diagnosed with Brugada syndrome ECG: electrocardiogram; EP: electrophysiology; ICD: implantable cardioverter-defibrillator; SCD: sudden cardiac death; VF: ventricular fibrillation; VT: ventricular tachycardia Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate

26. Clinical Approach to Brugada Syndrome ECG: electrocardiogram; ICD: implantable cardioverter-defibrillator; VT: ventricular tachycardia; NSAID: nonsteroidal anti-inflammatory drug. * Acetaminophen preferred; NSAID may be added if needed in absence of risk factors for NSAID toxicity. Δ High-risk features include sudden cardiac arrest, arrhythmogenic syncope, documented sustained VT, and family history of  Brugada syndrome. § Quinidine oral dose is 1 to 1.5 g/day of quinidine sulfate or 600 to 900 mg/day of hydroquinidine (not available in the United States), typically divided into three to four equal daily doses. Small studies have suggested that lower doses of quinidine sulfate (300 to 600 mg/day) may be effective in some patients. Strength of quinidine products available outside the United States may be expressed as salt or quinidine base; refer to local labeling for equivalence before use. ¥ Amiodarone oral dose is 200 mg daily after an initial oral loading dose (typically 400 mg twice daily or 200 mg three times daily for one to two weeks). ‡ Significant burden of  sustained ventricular tachycardia . Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate

27. FOLLOW UP C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 8 , N O . 3 , 2 0 2 2 Krahn et al

28. CPVT: catecholaminergic polymorphic ventricular tachycardia LQT : long QT syndrome BrS , Brugada syndrome ACS, acute coronary syndrome HCM , hypertrophic cardiomyopathy DCM, dilated cardiomyopathy ARVC , arrhythmogenic right ventricular cardiomyopathy rTOF , repaired tetralogy of Fallot PVT, polymorphic ventricular tachycardia MVT , monomorphic ventricular tachycardia 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death | European Heart Journal | Oxford Academic ( oup.com )

29. FOLLOW UP Educate the patient and relatives about the nature of the disease, how to recognize the symptoms and avoid provoking factors. Screening relatives (first-degree relatives) Clinical symptoms ECG Positive results → risk stratification Indeterminate results → should undergo drug-challenge testing. Negative results no history of syncope + a normal ECG → negative screening result With clinical symptom + normal ECG → repeat every one to two years until at least the fifth decade of life

30. Genetic testing? Brugada syndrome Definition : The Brugada syndrome is an  autosomal dominant   genetic disorder with variable expression characterized by abnormal findings on the surface  electrocardiogram  ( ECG ) in conjunction with an increased risk of  ventricular tachyarrhythmias  and  sudden cardiac death. Mutations in SCN5A, SCN10A, which encode subunits of sodium channels in the epicardial, endocardial and M cells of ventricular myocardium, which leads to the decrease of action potential duration (Na channel – depolarization phase) and the relative increase in the transient outward current (K channel – repolarization phase). H yperthermia causes changes in sodium current function; a reduction in sodium current results in changes to the action potential predisposing to ventricular fibrillation.

31. Genetic testing? Perform genetic testing for the proband (the affected patient) with Brugada syndrome. If a pathogenic variant is identified in the proband, then test their first-degree relatives (parents, siblings, children) for the specific variant found in the proband. This is called targeted genetic testing. However, universal genetic testing of asymptomatic first-degree relatives is not recommended, even if the proband has a confirmed diagnosis of Brugada syndrome but no pathogenic variant is identified. The rationale provided is that evidence does not support universal genetic testing of asymptomatic relatives, as the presence of potentially pathogenic variants in SCN5A or KCNH2 genes did not significantly increase the risk of being diagnosed with an arrhythmia syndrome in the study cited.

32. What is the chance of seeing this pattern and syndrome again? - Epidemiology Prevalence of Brugada pattern: 0.1 and 1 percent based on the studied populations, Brugada syndrome is significantly lower. Male > female Age at diagnosis - diagnosed in adulthood - the average patient age was 41 years (+-15).

33. Key takeaways

34. Key takeaways Thorough, systematic history taking is critical. Recognize the Brugada pattern on ecg Risk stratify patients with Brugada pattern. Acute management plan and follow up.