Dysrhythmia in Infancy
Dysrhythmia in Infancy
Although the mean age of diagnosis is around 40 years, Brugada syndrome is known to affect children as young as 1 year of age (Campuzano, Brugada, & Iglesias, 2010). In 17% to 42% of affected individuals, the primary presenting symptom is syncope and/or cardiac arrest as a result of a polymorphic VT or ventricular fibrillation (Benito, Brugada, Brugada, & Brugada, 2008). Additionally, these arrhythmic events tend to occur during periods of rest or sleep, which suggests that vagal tone and activity play an important role in the development of arrhythmias associated with Brugada syndrome (Benito et al., 2008). Fever also has been shown to trigger arrhythmias in these patients, especially in pediatric patients (Benito et al., 2008). The low cardiac output from this dysrhythmia can cause seizures, further complicating the patient's presentation (Skinner et al., 2007). Brugada syndrome affects a disproportionate number of males, suggesting sex-related differences in the ionic currents and/or hormones, specifically testosterone (Benito et al., 2008).
Brugada syndrome is an obscure clinical diagnosis that is characterized by ECG changes and sudden cardiac death (Napolitano & Priori, 2006). Discovered by the Brugada brothers, it was first described in 1992 as a clinical entity characterized by a typical ECG pattern of ST segment elevation in leads V1 to V3 and incomplete or complete RBBB (Napolitano & Priori, 2006). After many case reports and further research on this disease, formal diagnostic criteria were established by the Arrhythmia Working Group of the European Society of Cardiology. Diagnostic criteria are as follows: the appearance of a concave ST segment elevation greater than or equal to 2 mm that is followed by a negative T wave that is present in one or more right precordial leads (V1 to V3) and either documented ventricular arrhythmias, a family history of sudden cardiac death before the age of 45 years, or arrhythmia-related symptoms such as syncope or nocturnal agonal respirations (Benito et al., 2008). The exact prevalence is unknown because of the many suspected asymptomatic undiagnosed individuals. The suggested prevalence of Brugada syndrome is anywhere from 5/1000 in White persons and up to 14/1000 in persons of Japanese descent (Napolitano & Priori, 2006).
Brugada syndrome is a dysfunction of a cardiac channel that is involved in the action potential, resulting in the development of dysrhythmias. For an action potential to be normal, there must be a delicate balance of the inflow of sodium and calcium and the outflow of potassium (Viskin, 2007). In 1998, the first gene mutation related to Brugada syndrome was identified in the SCN5A gene, a cardiac sodium channel gene (Benito et al., 2008). Persons with this mutated gene have a reduction in the inflow of sodium, resulting in a disproportionate action potential, which allows for the polymorphic VT seen in Brugada syndrome (Viskin, 2007). Currently, only 20% of persons with known Brugada syndrome have the SCN5A mutation (Napolitano & Priori, 2006). A second gene mutation was discovered in 2002 on the GPD1-L gene, which is responsible for the trafficking of the cardiac sodium channel to the plasma membrane (London et al., 2007). Research also has linked mutations in the cardiac calcium channel, CACNA1c, to a syndrome with overlapping short QT and the Brugada ECG pattern (Benito et al., 2008). This finding suggests that Brugada syndrome may be a sodium channelopathy and an imbalance in the sodium and calcium inflows and potassium outflows during the action potential (Benito et al., 2008).
Patients with known Brugada syndrome who experience multiple dysrhythmias or have a history of syncope require aggressive treatment. Management goals include prevention and treatment of potentially life-threatening dysrhythmias. In the event of an acute electrical storm in a patient with Brugada syndrome, isoproterenol infusion has been shown to be beneficial. A β-adrenergic agonist, isoproterenol, enhances the L-type calcium channel, which in turn will improve ventricular repolarization and help normalize the ECG (Riera et al., 2007). Once NSR and stability have been achieved with an isoproterenol infusion, the patient must have therapeutic levels of an oral antiarrhythmic before the infusion can be discontinued.
Quinidine has been reported to prevent the occurrence of dysrhythmias associated with Brugada syndrome (Zipes et al., 2006). Quinidine is a class 1a antiarrhythmic agent with anticholinergic and negative inotrope properties (Takemoto, Hodding, & Kraus, 2011). Although the exact mechanism of action is unknown, it has been hypothesized that quinidine inhibits the transient outward current of potassium during the action potential, which restores isometric electrical conduction and prolongs the ventricular refractory period (Belhassen, Glick, & Viskin, 2004). The use of quinidine, however, does not come without potential serious adverse effects, including QT prolongation and torsades de pointes, as well as minor adverse effects such as nausea and diarrhea.
Despite the known positive outcomes achieved with the use of quinidine, patients who have experienced a dysrhythmia or syncopal episode should be implanted with an ICD. According to Zipes and colleagues (2006), ICD implantation is recommended for persons with Brugada syndrome who have experienced any of the following conditions: previous cardiac arrest while receiving chronic medical therapy; spontaneous ST-segment elevation in V1, V2, or V3 leads when syncope has occurred with or without mutations in the SCN5A gene and when a reasonable expectation of survival exists with a good functional status of more than 1 year; or when VT is documented that did not result in cardiac arrest and a reasonable expectation of survival exists with a good functional status of more than 1 year. Although ICD implantation is associated with improved outcomes, complications can occur, including infection, inappropriate activation and delivery of defibrillation discharges, and the need for lifetime surgical procedures. Additionally, an increased rate of complications is seen among children with Brugada syndrome because of their young age at diagnosis and their active lifestyle, potentially resulting in lead dislodgement (Viskin et al., 2009).
Currently there is no standardized approach to follow-up in children after ICD implantation, and thus follow-up occurs in conjunction with the cardiologist and primary care provider (PCP). In this case study, the infant experienced an extended hospitalization and was discharged home with a prescription for quinidine, which requires monitoring serum levels; therefore follow-up by the cardiologist within 1 week was warranted. At each visit, the PCP should assess the patient's activity level, nutrition, medication adverse effects, serum quinidine levels, and caregiver coping strategies in the care of a medically fragile child. Follow-up usually is continued on a monthly basis until determined otherwise by the patient's cardiologist and PCP.
In addition, monitoring for complications associated with ICD implantation, including infection, inappropriate defibrillation discharges, and lead dislodgement, is important. The ICD device can be downloaded either at an office evaluation or over the telephone. Education of the family includes signs and symptoms that may indicate that the patient could be receiving defibrillation discharges from the ICD, such as sudden screaming or grabbing his or her chest. Also, in this particular case, achieving and maintaining therapeutic quinidine levels is critical because subtherapeutic levels put the patient at increased risk of dysrhythmias. Education regarding the importance of medication compliance and notifying the cardiologist of illness is critical to prevent complications.
The patient continues to do well at home. Initially he was readmitted 2 days after discharge because of concerns from his mother that his ICD was firing. Upon interrogation, it was discovered that the ICD was not firing; however, the patient's quinidine level was found to be subtherapeutic. Once titration of the quinidine led to therapeutic levels, the patient again was discharged home with bimonthly follow-up with his pediatric cardiologist, which includes interrogation of his ICD. At a subsequent follow-up visit, a β-blocker, metoprolol, was added to his antiarrhythmic regimen with good effect.
Although a great deal of data have been gathered regarding Brugada syndrome since its recognition, little is known regarding prognosis and life expectancy. According to Benito and colleagues (2008), clinical variables exist that have been shown to predict a worse outcome in patients diagnosed with Brugada syndrome, including the presence of symptoms before diagnosis, the appearance of a type-1 ECG at baseline, the inducibility of ventricular dysrhythmias during an EP study, and being male. Unfortunately, three of these four criteria apply to the patient in this case study.
Case Study Answers
1. What is Brugada Syndrome?
Although the mean age of diagnosis is around 40 years, Brugada syndrome is known to affect children as young as 1 year of age (Campuzano, Brugada, & Iglesias, 2010). In 17% to 42% of affected individuals, the primary presenting symptom is syncope and/or cardiac arrest as a result of a polymorphic VT or ventricular fibrillation (Benito, Brugada, Brugada, & Brugada, 2008). Additionally, these arrhythmic events tend to occur during periods of rest or sleep, which suggests that vagal tone and activity play an important role in the development of arrhythmias associated with Brugada syndrome (Benito et al., 2008). Fever also has been shown to trigger arrhythmias in these patients, especially in pediatric patients (Benito et al., 2008). The low cardiac output from this dysrhythmia can cause seizures, further complicating the patient's presentation (Skinner et al., 2007). Brugada syndrome affects a disproportionate number of males, suggesting sex-related differences in the ionic currents and/or hormones, specifically testosterone (Benito et al., 2008).
Brugada syndrome is an obscure clinical diagnosis that is characterized by ECG changes and sudden cardiac death (Napolitano & Priori, 2006). Discovered by the Brugada brothers, it was first described in 1992 as a clinical entity characterized by a typical ECG pattern of ST segment elevation in leads V1 to V3 and incomplete or complete RBBB (Napolitano & Priori, 2006). After many case reports and further research on this disease, formal diagnostic criteria were established by the Arrhythmia Working Group of the European Society of Cardiology. Diagnostic criteria are as follows: the appearance of a concave ST segment elevation greater than or equal to 2 mm that is followed by a negative T wave that is present in one or more right precordial leads (V1 to V3) and either documented ventricular arrhythmias, a family history of sudden cardiac death before the age of 45 years, or arrhythmia-related symptoms such as syncope or nocturnal agonal respirations (Benito et al., 2008). The exact prevalence is unknown because of the many suspected asymptomatic undiagnosed individuals. The suggested prevalence of Brugada syndrome is anywhere from 5/1000 in White persons and up to 14/1000 in persons of Japanese descent (Napolitano & Priori, 2006).
Brugada syndrome is a dysfunction of a cardiac channel that is involved in the action potential, resulting in the development of dysrhythmias. For an action potential to be normal, there must be a delicate balance of the inflow of sodium and calcium and the outflow of potassium (Viskin, 2007). In 1998, the first gene mutation related to Brugada syndrome was identified in the SCN5A gene, a cardiac sodium channel gene (Benito et al., 2008). Persons with this mutated gene have a reduction in the inflow of sodium, resulting in a disproportionate action potential, which allows for the polymorphic VT seen in Brugada syndrome (Viskin, 2007). Currently, only 20% of persons with known Brugada syndrome have the SCN5A mutation (Napolitano & Priori, 2006). A second gene mutation was discovered in 2002 on the GPD1-L gene, which is responsible for the trafficking of the cardiac sodium channel to the plasma membrane (London et al., 2007). Research also has linked mutations in the cardiac calcium channel, CACNA1c, to a syndrome with overlapping short QT and the Brugada ECG pattern (Benito et al., 2008). This finding suggests that Brugada syndrome may be a sodium channelopathy and an imbalance in the sodium and calcium inflows and potassium outflows during the action potential (Benito et al., 2008).
2. How is Brugada Syndrome Diagnosed and Managed?
Patients with known Brugada syndrome who experience multiple dysrhythmias or have a history of syncope require aggressive treatment. Management goals include prevention and treatment of potentially life-threatening dysrhythmias. In the event of an acute electrical storm in a patient with Brugada syndrome, isoproterenol infusion has been shown to be beneficial. A β-adrenergic agonist, isoproterenol, enhances the L-type calcium channel, which in turn will improve ventricular repolarization and help normalize the ECG (Riera et al., 2007). Once NSR and stability have been achieved with an isoproterenol infusion, the patient must have therapeutic levels of an oral antiarrhythmic before the infusion can be discontinued.
Quinidine has been reported to prevent the occurrence of dysrhythmias associated with Brugada syndrome (Zipes et al., 2006). Quinidine is a class 1a antiarrhythmic agent with anticholinergic and negative inotrope properties (Takemoto, Hodding, & Kraus, 2011). Although the exact mechanism of action is unknown, it has been hypothesized that quinidine inhibits the transient outward current of potassium during the action potential, which restores isometric electrical conduction and prolongs the ventricular refractory period (Belhassen, Glick, & Viskin, 2004). The use of quinidine, however, does not come without potential serious adverse effects, including QT prolongation and torsades de pointes, as well as minor adverse effects such as nausea and diarrhea.
Despite the known positive outcomes achieved with the use of quinidine, patients who have experienced a dysrhythmia or syncopal episode should be implanted with an ICD. According to Zipes and colleagues (2006), ICD implantation is recommended for persons with Brugada syndrome who have experienced any of the following conditions: previous cardiac arrest while receiving chronic medical therapy; spontaneous ST-segment elevation in V1, V2, or V3 leads when syncope has occurred with or without mutations in the SCN5A gene and when a reasonable expectation of survival exists with a good functional status of more than 1 year; or when VT is documented that did not result in cardiac arrest and a reasonable expectation of survival exists with a good functional status of more than 1 year. Although ICD implantation is associated with improved outcomes, complications can occur, including infection, inappropriate activation and delivery of defibrillation discharges, and the need for lifetime surgical procedures. Additionally, an increased rate of complications is seen among children with Brugada syndrome because of their young age at diagnosis and their active lifestyle, potentially resulting in lead dislodgement (Viskin et al., 2009).
3. What Would the Management Plan be for This Child?
Currently there is no standardized approach to follow-up in children after ICD implantation, and thus follow-up occurs in conjunction with the cardiologist and primary care provider (PCP). In this case study, the infant experienced an extended hospitalization and was discharged home with a prescription for quinidine, which requires monitoring serum levels; therefore follow-up by the cardiologist within 1 week was warranted. At each visit, the PCP should assess the patient's activity level, nutrition, medication adverse effects, serum quinidine levels, and caregiver coping strategies in the care of a medically fragile child. Follow-up usually is continued on a monthly basis until determined otherwise by the patient's cardiologist and PCP.
In addition, monitoring for complications associated with ICD implantation, including infection, inappropriate defibrillation discharges, and lead dislodgement, is important. The ICD device can be downloaded either at an office evaluation or over the telephone. Education of the family includes signs and symptoms that may indicate that the patient could be receiving defibrillation discharges from the ICD, such as sudden screaming or grabbing his or her chest. Also, in this particular case, achieving and maintaining therapeutic quinidine levels is critical because subtherapeutic levels put the patient at increased risk of dysrhythmias. Education regarding the importance of medication compliance and notifying the cardiologist of illness is critical to prevent complications.
The patient continues to do well at home. Initially he was readmitted 2 days after discharge because of concerns from his mother that his ICD was firing. Upon interrogation, it was discovered that the ICD was not firing; however, the patient's quinidine level was found to be subtherapeutic. Once titration of the quinidine led to therapeutic levels, the patient again was discharged home with bimonthly follow-up with his pediatric cardiologist, which includes interrogation of his ICD. At a subsequent follow-up visit, a β-blocker, metoprolol, was added to his antiarrhythmic regimen with good effect.
Although a great deal of data have been gathered regarding Brugada syndrome since its recognition, little is known regarding prognosis and life expectancy. According to Benito and colleagues (2008), clinical variables exist that have been shown to predict a worse outcome in patients diagnosed with Brugada syndrome, including the presence of symptoms before diagnosis, the appearance of a type-1 ECG at baseline, the inducibility of ventricular dysrhythmias during an EP study, and being male. Unfortunately, three of these four criteria apply to the patient in this case study.
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