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A case study of Brugada syndrome
A Case Study of Brugada Syndrome Donna L. Robinson, BS, BSN, RN, A-EMT, CFRN, and Benjamin Tung, BS, RN, A-EMT, CFRN
Brugada syndrome is a little-known hereditary disease that causes severe cardiac rhythm disturbances, eventually resulting in sudden unexpected cardiac death in apparently healthy individuals.1-3 The following is a case study of a young man diagnosed with Brugada syndrome after sustaining an unwitnessed arrest.
Case Study AB is a 27-year-old man recently discharged from a longterm substance abuse rehabilitation facility with a long history of ethanol and intravenous drug use. Approximately 20 minutes after being dropped off at a restaurant, he was found unresponsive in the bathroom. EMS arrived shortly thereafter and determined the patient was in full arrest. Paramedics provided ACLS, including endotracheal intubation, CPR, and IV access. Three mg of epinephrine, 1 mg of atropine, and 6 mg of narcan were given intravenously with a return of a perfusing rhythm en route to the local hospital. The patient maintained a Glasgow Coma Scale (GCS) of 3 S/P arrest. On arrival at the community hospital, additional IV access was secured, and radiologic studies, including a head CT and chest X-ray, were obtained. An attempt to secure a right subclavian central venous line was unsuccessful. Arrangements were made to transfer this patient to a tertiary care facility by air medical transport. When the air-medical team arrived, the patient was mechanically ventilated with a VT 600 L, AC 12, 100% FiO2. The patient was breathing rapidly above the ventilator. His breath sounds were very course, wet, and decreased bilaterally with an O2 sat of 86%. He was tachycardic to the 170s, diaphoretic, and normotensive with an adequate urine output. Neurologically, the patient did not respond to painful stimuli, he had a GCS of 3, and his pupils were 4 mm bilaterally and nonreactive. An EKG revealed a right bundle branch block and ST segment elevation in leads V1 to V3. The community hospital personnel reported that the patient was maintaining an oxygen saturation of 95% or better until just before the flight team arrived. They also said he had a period of hypertension that responded to a brief infusion of esmolol, which was now turned off. He had remained unresponsive, pupils fixed at 4 mm bilaterally, throughout his course there. The head CT revealed diffuse cerebral edema, May-June 2003
decreased ventricles, and ablation of sulci consistent with an anoxic brain injury. The flight team suctioned him for copious, thick, pink, frothy secretions, and his breath sounds improved bilaterally. The patient was paralyzed adequately and sedated to control his metabolic demands and tachypnea in an effort to better ventilate and oxygenate him. He was suctioned a second time, his VT increased to 700L, and 10 of PEEP was added for improved oxygenation and ventilation in light of his profound pulmonary edema. The patient responded with increased O2 saturation into the mid-90s and better movement of air throughout the lung fields. The patient was packaged for transport and flown to a university hospital tertiary care facility, where he was admitted to the critical care medical unit (CCMU). A 12-lead EKG was done and showed a bundle branch block and ST elevation in V1-V3—consistent Brugada syndrome. A cerebral perfusion study conducted the next day revealed no blood flow to the brain, and subsequently, life support was withdrawn.
Discussion Brugada syndrome is a genetic mutation resulting in aberrant electrical conduction. More specifically, it alters the function of the sodium channel, producing a loss of sodium current. This loss leaves it unopposed, creating heterogeneity of refractory periods and a perfect substrate for arrhythmias based on phase 2 re-entry.2, 4,6 There is no structural cardiac abnormality. The result is sudden cardiac death.3-6 Brugada syndrome is responsible for 4%-12% of unexpected sudden deaths and up to 50% of all sudden death in pa-
Survival Flight, University of Michigan, Ann Arbor, Mich. Address for correspondence: Donna L. Robinson, Survival Flight, University of Michigan Health Systems, 1500 E. Medical Center Dr., Ann Arbor, MI 48109 Copyright 2003 by Air Medical Journal Associates 1067-991X/2003/$30.00 + 0 doi:10.1067/mmj.2003.41
47
Figure. Right bundle branch block and ST segment elevation
tients with apparently normal hearts. The incidence may even be higher in the younger population.1,5 Of note, the Centers for Disease Control reports this syndrome is the most common cause of sudden death in individuals younger than 50 in South Asia with no underlying cardiac disease. In Thailand, this form of death was known as lai tai (death during sleep), in the Philippines as bangungut (scream followed by sudden death during sleep), and in Japan as pokkuri (unexpected sudden death at night).4 The incidence and prevalence of this disease is difficult to determine because of the variability in presentation. Patients may present with the diagnostic electrocardiogram featuring a right bundle branch block and ST segment elevation in leads V1 to V3 (Figure 1) or with a normal EKG. The patient may be asymptomatic or sustain episodes of polymorphic ventricular tachycardia-ventricular fibrillation. When the episodes end suddenly, the patient develops syncopal attacks. When the episodes are sustained, full-blown cardiac arrest and sudden death occur.1,2,4,7,8 Asymptomatic individuals with EKG changes characteristic of Brugada syndrome often are diagnosed inadvertently while being evaluated for other medical issues or because sudden cardiac death has occurred in a family member diagnosed with the disease. Symptomatic individuals often are diagnosed while being evaluated for syncopal episodes or they have a diagnosis of idiopathic ventricular fibrillation. Asymptomatic patients with Brugada syndrome-type EKG changes will become symptomatic after the injection of ajamaline, flecainide, or procainamide. The pharmacologic test is so specific that it is recommended in all patients who present with a history of syncope of unknown origin or ventricular fibrillation of unknown cause.1,9 Individuals also may present with a typical electrocardiogram or with typical Brugada-type EKG changes that are present intermittently. These individuals are exhibiting the charac48
teristic EKG pattern after pharmacologic injection previously described. The EKG pattern is variable over time, depending on the autonomic interaction and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. When the heart rate decreases, the ST segment elevation increases; when the heart rate increases, the ST segment elevation decreases.4 Because the electrocardiogram may be completely normal at times and abnormal at others, several explanations have been offered related to Brugada syndrome. Autonomic changes and body temperature influence the electrocardiogram, as do adrenergic and vagal stimulation. An increase in heart rate decreases ST segment elevation, while a decrease in heart rate increases it. It becomes more prominent at slow rates, increasing heterogeneity and ST segment elevation. These data also agree with the clinical observations documenting a bradycardia-dependency and a higher incidence of sudden death during sleep in patients with this syndrome.4 Normalization of the ST segment during exercise is the most common finding in patients with this syndrome. These findings are logical because both an increase in heart rate and adrenergic stimulation increases ST segment elevation. Regardless of current symptoms or symptoms produced by pharmacologic induction, up to 40% of individuals with a diagnostic pattern of right bundle branch block and elevated ST segment in V1 to V3 will develop a new or first episode of polymorphic ventricular tachycardia or sudden death during the next 2- to 3-year follow-up.4,6,7 Phase 2 re-entry is believed to underlie the ventricular arrhythmias because these tachycardias can be reproduced by programmed electrical stimulation. Brugada syndrome has a very poor prognosis when left untreated: one-third of patients having suffered from syncopal episodes or resuscitated from near-sudden death develop a new episode of polymorphic ventricular tachycardia within 2 years. Prognosis of asymptomatic individuals with typical Air Medical Journal 22:3
electrocardiogram also is poor. In spite of not having any previous symptoms, one-third of these individuals present with a first polymorphic ventricular tachycardia of ventricular fibrillation within 2 years of follow-up.4 Treatment by antiarrhythmic drugs (amiodarone or betablockers) does not protect against sudden cardiac death. The only available treatment is the implantable cardioverter-defibrillator. When defibrillators are implanted, total mortality in patients with Brugada syndrome has been 0% with up to 10 years follow-up.4,8,9 These results are not surprising because these patients are young and usually devoid of other diseases, their heart is structurally normal, and they have no coronary artery disease.1-9 The syndrome of right bundle branch block, ST segment elevation from V1 to V3, and sudden death is a new entity. This disease is determined genetically, and the incidence of sudden death is very high. The EKG is a marker of sudden death in symptomatic and asymptomatic individuals.1,4,7-9 Concerns arise in the treatment of asymptomatic individuals. Because of this, three groups of patients should be distinguished: • Symptomatic individuals with the disease who require an implantable cardioverter-defibrillator. Patients with transient normalization of the EKG during follow up have the same prognosis as patients with a permanently abnormal electrocardiogram. • Asymptomatic patients with a spontaneous abnormal electrocardiogram and inducible polymorphic ventricular tachycardia or ventricular fibrillation who also require an implantable defibrillators.
• Asymptomatic individuals with an abnormal electrocardiogram only after drug challenge and no inducible ventricular arrhythmias who should not be treated but followed carefully for development of symptoms suggesting arrhythmias (syncope) Relatives of individuals diagnosed with Brugada’a syndrome should be screened using pharmacologic means (sodium channel blocker).9 These recommendations may change, depending on the availability of new data.
References 1. Brugada P, Brugada R, Brugada J. Sudden death in patients and relatives with the syndrome of right bundle branch block, ST segment elevation in the precordial leads V1 to V3 and sudden death. Eur Heart J 2000;21:321-6. 2. Brugada R, Brugada J, Antelevtich C, Kirsch G, Potenza D, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510-5. 3. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992;20:1391-6. 4. Brugada R. Brugada syndrome. Molecular Cardiology Laboratory USA. Available at: www.brugada.crita.be/aboutthissite/about.html. 5. Brugada R, Roberts R. The molecular genetics of arrhythmias and sudden death. Clin Cardiol 1998;21:553-60. 6. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293-6. 7. Dumaine R, Towbin J, Brugada P, Vatta M, Nesterenko D, et al. Ionic mechanism responsible for electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circulation Res 1999;85:803-9. 8. Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST segment elevation in leads V1 through V3. Circulation 1998;97:457-60. 9. Brugada P. Brugada syndrome: an electrocardiographic diagnosis not to be missed. Heart 2000;84(1):1-2.
Brugada syndrome is a little-known hereditary disease that causes severe cardiac rhythm disturbances, eventually resulting in sudden unexpected cardiac death in apparently healthy individuals.1-3 The following is a case study of a young man diagnosed with Brugada syndrome after sustaining an unwitnessed arrest.
Case Study AB is a 27-year-old man recently discharged from a longterm substance abuse rehabilitation facility with a long history of ethanol and intravenous drug use. Approximately 20 minutes after being dropped off at a restaurant, he was found unresponsive in the bathroom. EMS arrived shortly thereafter and determined the patient was in full arrest. Paramedics provided ACLS, including endotracheal intubation, CPR, and IV access. Three mg of epinephrine, 1 mg of atropine, and 6 mg of narcan were given intravenously with a return of a perfusing rhythm en route to the local hospital. The patient maintained a Glasgow Coma Scale (GCS) of 3 S/P arrest. On arrival at the community hospital, additional IV access was secured, and radiologic studies, including a head CT and chest X-ray, were obtained. An attempt to secure a right subclavian central venous line was unsuccessful. Arrangements were made to transfer this patient to a tertiary care facility by air medical transport. When the air-medical team arrived, the patient was mechanically ventilated with a VT 600 L, AC 12, 100% FiO2. The patient was breathing rapidly above the ventilator. His breath sounds were very course, wet, and decreased bilaterally with an O2 sat of 86%. He was tachycardic to the 170s, diaphoretic, and normotensive with an adequate urine output. Neurologically, the patient did not respond to painful stimuli, he had a GCS of 3, and his pupils were 4 mm bilaterally and nonreactive. An EKG revealed a right bundle branch block and ST segment elevation in leads V1 to V3. The community hospital personnel reported that the patient was maintaining an oxygen saturation of 95% or better until just before the flight team arrived. They also said he had a period of hypertension that responded to a brief infusion of esmolol, which was now turned off. He had remained unresponsive, pupils fixed at 4 mm bilaterally, throughout his course there. The head CT revealed diffuse cerebral edema, May-June 2003
decreased ventricles, and ablation of sulci consistent with an anoxic brain injury. The flight team suctioned him for copious, thick, pink, frothy secretions, and his breath sounds improved bilaterally. The patient was paralyzed adequately and sedated to control his metabolic demands and tachypnea in an effort to better ventilate and oxygenate him. He was suctioned a second time, his VT increased to 700L, and 10 of PEEP was added for improved oxygenation and ventilation in light of his profound pulmonary edema. The patient responded with increased O2 saturation into the mid-90s and better movement of air throughout the lung fields. The patient was packaged for transport and flown to a university hospital tertiary care facility, where he was admitted to the critical care medical unit (CCMU). A 12-lead EKG was done and showed a bundle branch block and ST elevation in V1-V3—consistent Brugada syndrome. A cerebral perfusion study conducted the next day revealed no blood flow to the brain, and subsequently, life support was withdrawn.
Discussion Brugada syndrome is a genetic mutation resulting in aberrant electrical conduction. More specifically, it alters the function of the sodium channel, producing a loss of sodium current. This loss leaves it unopposed, creating heterogeneity of refractory periods and a perfect substrate for arrhythmias based on phase 2 re-entry.2, 4,6 There is no structural cardiac abnormality. The result is sudden cardiac death.3-6 Brugada syndrome is responsible for 4%-12% of unexpected sudden deaths and up to 50% of all sudden death in pa-
Survival Flight, University of Michigan, Ann Arbor, Mich. Address for correspondence: Donna L. Robinson, Survival Flight, University of Michigan Health Systems, 1500 E. Medical Center Dr., Ann Arbor, MI 48109 Copyright 2003 by Air Medical Journal Associates 1067-991X/2003/$30.00 + 0 doi:10.1067/mmj.2003.41
47
Figure. Right bundle branch block and ST segment elevation
tients with apparently normal hearts. The incidence may even be higher in the younger population.1,5 Of note, the Centers for Disease Control reports this syndrome is the most common cause of sudden death in individuals younger than 50 in South Asia with no underlying cardiac disease. In Thailand, this form of death was known as lai tai (death during sleep), in the Philippines as bangungut (scream followed by sudden death during sleep), and in Japan as pokkuri (unexpected sudden death at night).4 The incidence and prevalence of this disease is difficult to determine because of the variability in presentation. Patients may present with the diagnostic electrocardiogram featuring a right bundle branch block and ST segment elevation in leads V1 to V3 (Figure 1) or with a normal EKG. The patient may be asymptomatic or sustain episodes of polymorphic ventricular tachycardia-ventricular fibrillation. When the episodes end suddenly, the patient develops syncopal attacks. When the episodes are sustained, full-blown cardiac arrest and sudden death occur.1,2,4,7,8 Asymptomatic individuals with EKG changes characteristic of Brugada syndrome often are diagnosed inadvertently while being evaluated for other medical issues or because sudden cardiac death has occurred in a family member diagnosed with the disease. Symptomatic individuals often are diagnosed while being evaluated for syncopal episodes or they have a diagnosis of idiopathic ventricular fibrillation. Asymptomatic patients with Brugada syndrome-type EKG changes will become symptomatic after the injection of ajamaline, flecainide, or procainamide. The pharmacologic test is so specific that it is recommended in all patients who present with a history of syncope of unknown origin or ventricular fibrillation of unknown cause.1,9 Individuals also may present with a typical electrocardiogram or with typical Brugada-type EKG changes that are present intermittently. These individuals are exhibiting the charac48
teristic EKG pattern after pharmacologic injection previously described. The EKG pattern is variable over time, depending on the autonomic interaction and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. When the heart rate decreases, the ST segment elevation increases; when the heart rate increases, the ST segment elevation decreases.4 Because the electrocardiogram may be completely normal at times and abnormal at others, several explanations have been offered related to Brugada syndrome. Autonomic changes and body temperature influence the electrocardiogram, as do adrenergic and vagal stimulation. An increase in heart rate decreases ST segment elevation, while a decrease in heart rate increases it. It becomes more prominent at slow rates, increasing heterogeneity and ST segment elevation. These data also agree with the clinical observations documenting a bradycardia-dependency and a higher incidence of sudden death during sleep in patients with this syndrome.4 Normalization of the ST segment during exercise is the most common finding in patients with this syndrome. These findings are logical because both an increase in heart rate and adrenergic stimulation increases ST segment elevation. Regardless of current symptoms or symptoms produced by pharmacologic induction, up to 40% of individuals with a diagnostic pattern of right bundle branch block and elevated ST segment in V1 to V3 will develop a new or first episode of polymorphic ventricular tachycardia or sudden death during the next 2- to 3-year follow-up.4,6,7 Phase 2 re-entry is believed to underlie the ventricular arrhythmias because these tachycardias can be reproduced by programmed electrical stimulation. Brugada syndrome has a very poor prognosis when left untreated: one-third of patients having suffered from syncopal episodes or resuscitated from near-sudden death develop a new episode of polymorphic ventricular tachycardia within 2 years. Prognosis of asymptomatic individuals with typical Air Medical Journal 22:3
electrocardiogram also is poor. In spite of not having any previous symptoms, one-third of these individuals present with a first polymorphic ventricular tachycardia of ventricular fibrillation within 2 years of follow-up.4 Treatment by antiarrhythmic drugs (amiodarone or betablockers) does not protect against sudden cardiac death. The only available treatment is the implantable cardioverter-defibrillator. When defibrillators are implanted, total mortality in patients with Brugada syndrome has been 0% with up to 10 years follow-up.4,8,9 These results are not surprising because these patients are young and usually devoid of other diseases, their heart is structurally normal, and they have no coronary artery disease.1-9 The syndrome of right bundle branch block, ST segment elevation from V1 to V3, and sudden death is a new entity. This disease is determined genetically, and the incidence of sudden death is very high. The EKG is a marker of sudden death in symptomatic and asymptomatic individuals.1,4,7-9 Concerns arise in the treatment of asymptomatic individuals. Because of this, three groups of patients should be distinguished: • Symptomatic individuals with the disease who require an implantable cardioverter-defibrillator. Patients with transient normalization of the EKG during follow up have the same prognosis as patients with a permanently abnormal electrocardiogram. • Asymptomatic patients with a spontaneous abnormal electrocardiogram and inducible polymorphic ventricular tachycardia or ventricular fibrillation who also require an implantable defibrillators.
• Asymptomatic individuals with an abnormal electrocardiogram only after drug challenge and no inducible ventricular arrhythmias who should not be treated but followed carefully for development of symptoms suggesting arrhythmias (syncope) Relatives of individuals diagnosed with Brugada’a syndrome should be screened using pharmacologic means (sodium channel blocker).9 These recommendations may change, depending on the availability of new data.
References 1. Brugada P, Brugada R, Brugada J. Sudden death in patients and relatives with the syndrome of right bundle branch block, ST segment elevation in the precordial leads V1 to V3 and sudden death. Eur Heart J 2000;21:321-6. 2. Brugada R, Brugada J, Antelevtich C, Kirsch G, Potenza D, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510-5. 3. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992;20:1391-6. 4. Brugada R. Brugada syndrome. Molecular Cardiology Laboratory USA. Available at: www.brugada.crita.be/aboutthissite/about.html. 5. Brugada R, Roberts R. The molecular genetics of arrhythmias and sudden death. Clin Cardiol 1998;21:553-60. 6. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293-6. 7. Dumaine R, Towbin J, Brugada P, Vatta M, Nesterenko D, et al. Ionic mechanism responsible for electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circulation Res 1999;85:803-9. 8. Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST segment elevation in leads V1 through V3. Circulation 1998;97:457-60. 9. Brugada P. Brugada syndrome: an electrocardiographic diagnosis not to be missed. Heart 2000;84(1):1-2.