Case Discussion < Presentation of Case >      A 43-year-old Taiwanese male arrived at the emergency department (ED) after an episode of syncope while at work. The event was witnessed by several of the patient's co-workers, one of whom accompanied him to the ED and described the event. According to the description provided by his co-worker, the patient complained of nausea and dizziness during the afternoon meeting. At around 3 pm, the patient suddenly fell out of his chair and hit his head on the floor. He was found unconscious without seizure-like activities, including jerky body movements, tongue biting, or incontinence. After a while, the patient regained consciousness and was immediately fully alert without a period of confusion or garbled speech. The patient recalled that this was not the first episode and that he had experienced similar episodes over the past few years, but this was the first time he sought medical evaluation. The patient also indicated that his father died suddenly in his 40s, but he could not recall the cause of death. When presenting at the ED, the patient had no specific complaints other than a bruise on his forehead that resulted from the fall.      On physical examination, the patient was awake and alert. The heart rate was 76 beats per minute, the blood pressure 123/84 mm Hg, and the respiration 15 breaths per minute; the oxygen saturation was 100% while he was breathing ambient air. A lesion of ecchymosis of 3.5 cm in diameter was noted on his right forehead, with no hematoma, laceration, or tenderness to palpation. Cardiac auscultation revealed regular heart rhythm without murmurs or gallops and the chest examination showed no abnormal breath sounds. Results of the neurologic examination were also unremarkable, including normal cranial nerve function and motor and sensory functions.      A panel of blood tests was performed (Tables). The results of the complete blood cell (CBC) count as well as biochemistry were unremarkable. Two electrocardiograms (ECG) were performed, one while the patient was at the ED (see Figure 1) and the other 4 hours later (see Figure 2 ). < Laboratory data > CBC/DC: (Time: 4:21pm, September 10th, 2006, at the ED) WBC /μL 8100 Band % 0 RBC M/μL 4.22 Seg % 59 Hb g/dL 14.6 Lym % 36 Hct % 41.7 Mono % 3 MCV fl 88.3 Eos % 2 PLT. /μL 266000 Baso % 0 Biochemistry: (Time: 4:21pm, September 10th, 2006, at the ED) Alb          g/dL 3.8 T-Bil    mg/dL 0.6 BUN       mg/dL 18 K         mmol/L 3.8 Cre          mg/dL 0.9 ALT     U/L 33 Glucose   mg/dL 108 Cl        mmol/L 101 Na          mmol/L 142 AST    U/L 31 Mg          mmol/L 0.9 Ca       mmol/L 2.32 Serial cardiac enzyme levels (at the ED)   4:21am 09/10/2006 10:25m 09/10/2006 4:19pm 09/10/2006 10:22am 09/10/2006 CK (U/L) 113 115 110 99 CK-MB (U/L) 7 9 11 9 Troponin-I (U/L) 0.05 0.04 0.05 0.02 Artery blood gas (Time: 4:05 pm, September 10th, 2006, at the ED): pH: 7.41, PCO2: 39.6 mmHg, PO2: 88 mmHg, HCO3-: 23.7 meq/L Echocardiography (7:31pm, September 10th, 2008, at the ED): normal size of the left atrium and left ventricle (LV), with good contractility, No tricupid regurgitation. Coronary angiography (8:16am, September 11th, 2006): patent coronary arteries Magnetic resonance imaging of the heart (9:16am, September 12th, 2006): normal cardiac structure and systolic function of the LV and right ventricle. < Course and Treatment >      A consultation with an electrophysiologist was made, who suggested admission of the patient for observation. The follow-up ECG was normal (figure 2 ), and his serial examinations of cardiac enzymes as well as serum electrolytes were within the normal ranges for the next 24 hours (tables). He underwent an electrophysiologic study (EPS) on September 12th, 2006, which showed inducible ventricular fibrillation by rapid right ventricular pacing. It was decided that an implantable cardioverter defibrillator would be placed, considering the patient's family history of sudden cardiac death, clinical presentations, ECG patterns and EPS results. On September 13th, 2006, the patient was discharged, and it was advised that his family members be made aware of his diagnosis and treatment. < Discussion > The ECG findings (Figure 1 ) of this patient illustrates a downsloping ST-segment elevation in leads V1-V3, accompanied by a QRS morphology resembling that of a right bundle branch block (RBBB), those of which are characteristic of a Brugada-type pattern. In addition, the previous history of multiple episodes of unexplained syncope, as well as sudden cardiac death of his father suggests a diagnosis of the Brugada syndrome. Sudden cardiac death is uncommon in individuals with a structurally abnormal heart or without a history of coronary artery disease. Causes of SCD in these patients include: the Brugada syndrome, long-QT syndrome, and preexcitation syndromes. In 1992, Brugada and Brugada first reported a specific clinical entity of idiopathic ventricular fibrillation (VF) presenting with the ST segment elevation in leads V1 to V3, with or without right bundle branch block, and normal QT interval in the absence of structural heart disease or other reversible causes [1]. It was also reported that these patients died suddenly of VF and often in their sleep and associated clinical features included syncopal episodes, documented ventricular fibrillation, self-terminating polymorphic ventricular tachycardia (VT), a family history of sudden cardiac death in a relative aged less than 45 years, and evidence of ST-segment elevation in family members. Epidemiologic studies suggest that the disease might be responsible for nearly half of all sudden cardiac death in individuals without structural heart disease [2]. While the prevalence of the disease may be dependent on factors such as gender, age and ethnicity, the disease most commonly affects men whose average age at presentation is 30 years and is the most common cause of sudden cardiac death in young persons in South Asia. [3] The Brugada syndrome is caused by an autosomal-dominant genetic defect with incomplete penetrance that results in dysfunction or loss of function of the sodium channel, thereby reducing the sodium current available during phases 0 (upstroke) and 1 (early repolarization), leading to the development of malignant ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden cardiac death [4]. Underlying genetic components of the Brugada syndrome is still under investigation. Brugada et al. suggested that as in the long QT syndrome, the best candidate genes are those that are responsible for the formation of the cardiac action potential, namely the genes that encode for the cardiac ionic channels [4], with approximately 20-30% of cases demonstrating a loss-of-function mutation in the SCN5A gene [5, 6]. In many patients, electrocardiographic presentations of the Brugada syndrome show transient normalization. This, however, can be unmasked using sodium channel blockers such as flecainide, ajmaline or procainamide [6]. The diagnosis of Brugada syndrome should be considered in patients with a family history of sudden cardiac death, even in the presence of an initial normal ECG. Admission is not required for all patients presenting with syncope. However, like the patient in this case study, those with previous syncopal episodes as well as ECG abnormalities or a family history of sudden cardiac death should be hospitalized for investigations. To date, the only effective treatment of the Brugada Syndrome is the implantation of an automatic implantable cardioverter defibrillator (AICD). However, close follow-up without intervention has been recommended for asymptomatic patients with no family history of sudden cardiac death. In conclusion, this otherwise healthy patient with an episode of sudden unexpected syncope received a diagnosis of Brugada syndrome based on his family history of probable sudden cardiac death, previous syncopal episodes as well as ECG abnormalities. An AICD was placed without a formal EPS and the patient was discharged on the second day of implantation. < References > Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391-6. Brugada P, Brugada R, Brugada J. The Brugada syndrome. Curr Cardiol Rep 2000; 2:507-14. Nademanee, K, et al., Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 1997;96:2595-600. Brugada J, Brugada P, Brugada R. Brugada syndrome: the syndrome of right bundle branch block, ST segment elevation in V1 to V3 and sudden death. Indian Pacing Electrophysiol J 2001;1:6-11. Chen Q, et al. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature 1998;392:293-296. Gussak I, et al. The Brugada syndrome: clinical, electrophysiologic and genetic aspects. J Am Coll Cardiol 1999;33:5-15. 繼續教育考題 1. (E) Which of the following may NOT be considered in the differential diagnoses of sudden loss of consciousness?  A Myocardial infarction B Stroke C Life-threatening arrhythmias D Seizure E Urinary tract infection 2. (A) What is the patient's underlying disorder in this case presentation? A Brugada syndrome B Wolff-Parkinson-White syndrome C ST-segment elevation myocardial infarction D Ventricular tachycardia 3. (D) Which of the following electrocardiographic (ECG) abnormalities is NOT typically associated with the Brugada pattern?  A QRS morphology resembling a right bundle branch block (RBBB) B Downsloping ST-segment elevations in V1-V3 C Negative deflection of the T-wave in the affected precordial leads D Prolonged QT interval E None of the above 4. (E) Which of the following associated features is NOT required to define Brugada syndrome? A Previously documented ventricular fibrillation (VF) B A family history of sudden cardiac death in individuals who are aged less than 45 years C A history of syncopal episodes D Evidence of ST segment elevation in family members E A history of fever 5. (C) Which of the following is NOT correct?  A Brugada syndrome is autosomal dominant genetic disease with incomplete penetrance B 20-30% of patients with Brugada syndrome demonstrate a loss-of-function mutation in the SCN5A gene. C A patient with Brugada syndrome can not present with self-terminated ventricular tachycardia D The ECG of a patient with Brugada syndrome can present as a normal ECG 6. (D) Which of the following is NOT correct?  A The structure of the heart in patients with Brugada syndrome is usually normal. B Brugada syndrome mostly affects middle-age people who are aged 30 to 40 years C Brugada syndrome mostly affects men. D To date, the only effective treatment of patients with Brugada syndrome is flecainide.

答案解說 ( E ) Patients with urinary tract infection usually present with dysuria, frequency and urgency of urination. It rarely causes sudden loss of consciousness. ( A ) This patient had classic Brugada-type ECG presentation (a downsloping ST-segment elevation in leads V1-V3, accompanied by a QRS morphology resembling that of a right bundle branch block (RBBB) and a family history of sudden cardiac death. All imaging studies showed normal heart structure. All of the findings support the diagnosis of Brugada syndrome ( D ) The Brugada-type ECGs have normal QT intervals, unlike the long QT syndrome. ( E )Brugada syndrome presentation is usually related to abnormal EKG or ventricular arrhythmia. Fever is not one of the presentations. ( C ) As in this case, the patient may present with self-terminated ventricular tachycardia. So he regained consciousness without resuscitation. ( D ) To date, the only effective treatment is the implantation of an automatic implantable cardioverter defibrillator (AICD) to prevent the patient from sudden death.