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Cardiac channelopathies
CARDIAC GENETICS
Cardiac channelopathies
Key points
Simon Claridge
C
Cardiac channelopathies carry a risk of ventricular arrhythmia and sudden death
C
Patients who present with aborted sudden cardiac death almost always require an implantable cardioverter-defibrillator (ICD)
C
The great majority of asymptomatic channelopathy patients are at low risk of sudden death and generally do not require an ICD after clinical assessment
C
Targeted genetic testing should be considered for index patients; subsequent cascade screening may be of use
C
Long QT and Brugada syndromes are rare but important diagnoses that should be considered in the general medical environment
Arthur Yue
Abstract Cardiac channelopathies are inherited cardiac disorders associated with potentially life-threatening ventricular arrhythmias. They are caused by genetic mutations of ion channels that alter cardiac cell membrane potential and intracellular haemostasis, and include long QT syndromes (LQTSs), Brugada syndrome and the much rarer catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, short QT syndrome and early repolarization syndrome. Presentation of these varies widely from sudden cardiac death to incidental diagnosis at the time of electrocardiography. While they are rare, diagnosis and subsequent familial screening can have significant results for both the index patient and family members. A clear understanding of the cardiac action potential helps to clarify the pathological mechanism of arrhythmogenesis that characterizes these conditions. Risk stratification of adverse outcomes from these conditions is complex and often imprecise. Medical therapy and implantable cardioverter-defibrillators have a potential role in patient management. It is recommended that complex decisions relating to these patients be discussed in a multidisciplinary team environment wherever possible. Most of this review focuses on LQTS and Brugada syndrome as these are the most common forms of cardiac channelopathies.
Long QT syndrome (LQTS) LQTS is a rare cause of both syncope and sudden death, and has a prevalence of approximately 1:5000. At least 12 different genetic mutations have been identified, each resulting in delayed repolarization and prolongation of the QTc interval; this predisposes to early after-depolarization (EAD) in the prolonged phase 2 or 3 of the action potential (Figure 2). A causative genetic variant is identified in approximately 65% of patients. The prevalence and malignancy of LQTS is higher in women in general who have a normal QTc interval of 460e480 ms compared with 440 ms in men. These EADs can lead to torsades de pointes (a form of polymorphic ventricular tachycardia) and subsequent sudden death.
Keywords Action potential; Brugada syndrome; channelopathy; long QT syndrome; MRCP; sudden death; ventricular arrhythmia
Overview of the cardiac action potential
The ventricular myocyte action potential
The cardiac action potential of the human ventricular myocardium has five distinct temporal phases (Figure 1). Phase 0 corresponds to ventricular depolarization and represents the inward movement of sodium ions via fast sodium channels. Phase 1 is a brief period of fast repolarization as the sodium channels begin to close. Phase 2 is a longer plateau phase with gradual net outflow of current in which there is both inward flow of calcium ions via the L-type calcium channels and outward flow of potassium ions via the slowly activating delayed inward rectifier potassium channel. Phase 3 corresponds to repolarization via the rapidly activating delayed inward rectifier potassium channel, and phase 4 is the resting membrane potential.
+50
1 2
mV
0
0
Simon Claridge LLB MB BS MRCP is Clinical Fellow at the Department of Cardiology, University Hospital Southampton, UK. Competing interests: none declared.
4 –100
Arthur Yue MA DM FRCP FACC is a Consultant Cardiologist and Electrophysiologist, Department of Cardiology, University Hospital Southampton, UK. Competing interests: none declared.
MEDICINE 46:10
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–50
Figure 1
618
Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
LQTS 1e3 make up the vast majority of diagnoses, with LQTS 1 and 2 alone accounting for 65% of cases. The three dominant forms of the syndrome are inherited in an autosomal dominant manner, with mutations in KCNQ1, KCNH2 and SCN5A implicated in the pathogenesis of LQTS 1, 2 and 3, respectively. Prolongation of the QT interval is key to diagnosis, although it may periodically be absent in the same patient. The risk of arrhythmia is proportional to the degree of prolongation of the QT interval, and thus the duration of phase 2 of the action potential when there is risk of EAD and arrhythmia (Figure 3). While the diagnosis of LQTS can be unproblematic, it is often challenging, and the Schwartz criteria (Table 1) can be used to aid diagnosis: a diagnosis of LQTS is likely if the score is 4 or more, probable it if is 2e3 and unlikely if it is 1.1
Diagnosis can be further aided by adrenaline (epinephrine) and exercise testing in the 4th minute of recovery; both aim to identify paradoxical prolongation of the QT interval as the heart rate increases. Implantable cardioverter-defibrillators (ICDs) are recommended for all cardiac arrest survivors. b-Adrenoceptor blockers are recommended for patients with prolonged QTc and syncope, or genetically proven mutations even with a normal QTc. Nadolol has the strongest evidence base but propranolol can be used if nadolol is not available. If patients have further syncopal events or torsades de pointes while on b-blockers, left cardiac sympathetic denervation and/or an ICD should be strongly considered. It is important to remember that many medications can cause prolongation of the QT interval. These should therefore be excluded before a diagnosis of LQTS is made. In addition, they should be avoided in patients with an LQTS diagnosis. Relevant information can be obtained from national societies or online (e.g. www.qtdrugs.org). Family cascade screening is imperative using genetic testing in gene-positive index cases, but clinical phenotypic testing is valuable even if gene testing is negative.
Prolongation of phase 2, and thus the vulnerable area for EADs, in LQTS +50
Brugada syndrome Brugada syndrome is characterized by coved ST elevation (2 mm) in at least one right precordial lead (V1 or V2) placed at the fourth or higher intercostal space e the type 1 pattern. Type 2 and 3 forms have been described but are of clinical significance only when pharmacological provocation results in a type 1 appearance. The diagnosis relies on a type 1 electrocardiogram (ECG) plus one of syncope, nocturnal agonal respiration, similar ECG changes in family members or a family history of sudden cardiac death. The Shanghai score has been proposed to aid diagnosis based upon these variables in patients who are asymptomatic with a provoked type 1 Brugada ECG pattern.2 There is a male:female preponderance of about 9:1 and an increased prevalence in the South/South-East Asian population (See Figure 4). In contrast to LQTS, the genetic basis of Brugada syndrome is not monogeneic but highly complex. Numerous genes have been
1 2
mV
0
0
3
–50
4 –100 Figure 2
Figure 3 A 12-lead ECG from a patient with LQTS 1 (QTc ¼ 520 ms).
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Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
these should be treated aggressively in patients with the condition. The type 1 ECG can also be brought on by certain medications or mimicked by others; online resources (e.g. www. brugadadrugs.org) list medications that should be avoided in patients with Brugada syndrome. Most patients with Brugada syndrome have a low risk of sudden cardiac death (<1%/year). There is no established medical treatment for Brugada syndrome, although isoprenaline and quinidine have been used with some success in patients with electrical storm in the acute and subacute phases. To date, only ICDs have been shown to prevent sudden death in Brugada syndrome, and they are recommended in cardiac arrest survivors. Otherwise, risk stratification for primary prevention devices is challenging. Syncope in a patient with a spontaneous type 1 ECG conveys the highest risk of ventricular fibrillation (VF), whereas asymptomatic patients with induced type 1 ECGs have a low risk of VF. Decisions must be taken on an individual basis and are often informed by patient choice, particularly if there has been a death in the family. The role of electrophysiological studies in risk-stratifying patients is highly controversial.3 Epicardial catheter ablation of the right ventricular outflow tract is an exciting evolving management strategy that has been shown to eliminate the type 1 Brugada ECG pattern and terminate VF storms.
Schwartz criteria for diagnosing LQTS Criterion ECG findings (no QT-prolonging drugs) QTc >480 ms QTc 460e479 ms QTc 450e459 ms in men Torsades de pointes T wave alternans Notched T wave in three leads Bradycardia Clinical history Syncope with stress Syncope without stress Congenital deafness Family history Family members with score >3 Unexplained death in immediate family <30 years of age
Score
3 2 1 2 1 1 0.5 2 1 0.5 1 0.5
Table 1
implicated in the disease, particularly mutations in SCN5A. The genes that cause the condition are inherited in an autosomal dominant manner, but severity of phenotype does not appear to be inherited. It is now understood that abnormalities in phenotypic expression are the result of numerous genetic mutations that conflate in an additive genetic effect. The pathophysiological basis of Brugada syndrome is debated. Increasing pathological and imaging data suggest that structural right ventricular heart disease is common. As such, Brugada syndrome has also been regarded as a subcategory of arrhythmogenic right ventricular cardiomyopathy, as opposed to a pure channelopathy. In family members of patients with confirmed Brugada syndrome who have a normal ECG, pharmacological provocation using a sodium channel blocker (e.g. ajmaline, flecainide) can be performed as this can unmask a type 1 Brugada ECG pattern to aid diagnosis. A type 1 ECG can also be provoked by fevers, and
Miscellaneous conditions Several other rare channelopathies can result in sudden death. These include short QT syndrome, early repolarization syndrome and catcholaminergic polymorphic ventricular tachycardia: Short QT syndrome is very rare. Families typically have a QTc <320 ms and abnormal T waves. Inheritance is autosomal dominant with three genes implicated. ICDs are used to prevent sudden death in these patients. Early repolarization syndrome describes an ECG abnormality found in a proportion of survivors of sudden cardiac death with structurally normal hearts. The ECG shows elevation of the J point. Unfortunately, this is a common finding in the general population, and ECG characteristics
Figure 4 A 12-lead ECG from a patient with a type 1 Brugada pattern in leads V1, HV1 and HV2 (‘high’ V1 and V2 leads placed in the second intercostal spaces, and shown on this ECG instead of V5 and V6, respectively).
MEDICINE 46:10
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Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
Gene testing should be targeted, seeking advice from clinical geneticists before testing. Complex decisions should be taken in the context of the multidisciplinary team, with input from an expert in specialist inherited cardiac conditions A
that prophylactically identify patients at high risk remain to be determined. Catcholaminergic polymorphic ventricular tachycardia presents in children, often on exertion, and is characterized by exertional bi-directional ventricular tachycardia that degenerates into VF. The resting ECG is normal. Nadolol, ICDs and cervical sympathectomy have therapeutic roles.
KEY REFERENCES 1 Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88: 782e4. 2 Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge. J Arrhythm 2016; 32: 315e39. 3 Paul M, Gerss J, Schulze-Barh E, et al. Role of programmed ventricular stimulation in patients with Brugada syndrome: a metaanalysis of worldwide published data. Eur Heart J 2007; 28: 2126e33.
General clinical points for all channelopathies Syncope in children and young adults, particularly on exertion, demands investigation including an ECG. Channelopathies should be considered and diagnoses actively sought in patients with aborted sudden cardiac death who have structurally normal hearts and normal coronary arteries. Clinical consultations should consider diagnosis, risk stratification, need for gene testing and family screening.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. What is the next best step? A. Reassurance B. Send the patient for genetic testing C. Take a more thorough history D. Insert an implantable cardioverter-defibrillator E. Start b-adrenoceptor blocker therapy
Question 1 A 14-year-old girl presented with an episode of collapse and syncope on exertion. She was not taking any medications. Clinical examination was normal. Investigations ECG showed sinus rhythm and a prolonged QTc of 490 ms Magnetic resonance scan of the heart was normal
Question 3 A 25-year-old woman presented with an out-of-hospital ventricular fibrillation arrest. After a week on intensive care, she made a full neurological recovery.
What is the most important next step in her arrhythmia management? A. Take a family history B. Start nadolol therapy C. Perform an exercise or adrenaline test D. Insert an implantable cardioverter-defibrillator E. Discharge the girl
Investigations Continuous ECG monitoring was normal ECGs with exercise, ajmaline and adrenaline challenge were all normal Magnetic resonance scan of the heart was normal Coronary angiogram was normal
Question 2 A 19-year-old man presented for reassurance after the sudden unexpected death of his father at age 38 years. He has had seizures in the past. Clinical examination was normal.
What is the best next step for this patient prior to hospital discharge? A. Prescribe amiodarone B. Refer for urgent genetic testing C. Implant a loop recorder (ILR) D. Insert a transvenous implantable cardioverter-defibrillator (ICD) E. Insert a subcutaneous ICD
Investigations Resting ECG was normal and showed sinus rhythm An ajmaline challenge ECG showed a type 1 Brugada pattern
MEDICINE 46:10
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Ó 2018 Elsevier Ltd. All rights reserved.
Cardiac channelopathies
Key points
Simon Claridge
C
Cardiac channelopathies carry a risk of ventricular arrhythmia and sudden death
C
Patients who present with aborted sudden cardiac death almost always require an implantable cardioverter-defibrillator (ICD)
C
The great majority of asymptomatic channelopathy patients are at low risk of sudden death and generally do not require an ICD after clinical assessment
C
Targeted genetic testing should be considered for index patients; subsequent cascade screening may be of use
C
Long QT and Brugada syndromes are rare but important diagnoses that should be considered in the general medical environment
Arthur Yue
Abstract Cardiac channelopathies are inherited cardiac disorders associated with potentially life-threatening ventricular arrhythmias. They are caused by genetic mutations of ion channels that alter cardiac cell membrane potential and intracellular haemostasis, and include long QT syndromes (LQTSs), Brugada syndrome and the much rarer catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, short QT syndrome and early repolarization syndrome. Presentation of these varies widely from sudden cardiac death to incidental diagnosis at the time of electrocardiography. While they are rare, diagnosis and subsequent familial screening can have significant results for both the index patient and family members. A clear understanding of the cardiac action potential helps to clarify the pathological mechanism of arrhythmogenesis that characterizes these conditions. Risk stratification of adverse outcomes from these conditions is complex and often imprecise. Medical therapy and implantable cardioverter-defibrillators have a potential role in patient management. It is recommended that complex decisions relating to these patients be discussed in a multidisciplinary team environment wherever possible. Most of this review focuses on LQTS and Brugada syndrome as these are the most common forms of cardiac channelopathies.
Long QT syndrome (LQTS) LQTS is a rare cause of both syncope and sudden death, and has a prevalence of approximately 1:5000. At least 12 different genetic mutations have been identified, each resulting in delayed repolarization and prolongation of the QTc interval; this predisposes to early after-depolarization (EAD) in the prolonged phase 2 or 3 of the action potential (Figure 2). A causative genetic variant is identified in approximately 65% of patients. The prevalence and malignancy of LQTS is higher in women in general who have a normal QTc interval of 460e480 ms compared with 440 ms in men. These EADs can lead to torsades de pointes (a form of polymorphic ventricular tachycardia) and subsequent sudden death.
Keywords Action potential; Brugada syndrome; channelopathy; long QT syndrome; MRCP; sudden death; ventricular arrhythmia
Overview of the cardiac action potential
The ventricular myocyte action potential
The cardiac action potential of the human ventricular myocardium has five distinct temporal phases (Figure 1). Phase 0 corresponds to ventricular depolarization and represents the inward movement of sodium ions via fast sodium channels. Phase 1 is a brief period of fast repolarization as the sodium channels begin to close. Phase 2 is a longer plateau phase with gradual net outflow of current in which there is both inward flow of calcium ions via the L-type calcium channels and outward flow of potassium ions via the slowly activating delayed inward rectifier potassium channel. Phase 3 corresponds to repolarization via the rapidly activating delayed inward rectifier potassium channel, and phase 4 is the resting membrane potential.
+50
1 2
mV
0
0
Simon Claridge LLB MB BS MRCP is Clinical Fellow at the Department of Cardiology, University Hospital Southampton, UK. Competing interests: none declared.
4 –100
Arthur Yue MA DM FRCP FACC is a Consultant Cardiologist and Electrophysiologist, Department of Cardiology, University Hospital Southampton, UK. Competing interests: none declared.
MEDICINE 46:10
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–50
Figure 1
618
Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
LQTS 1e3 make up the vast majority of diagnoses, with LQTS 1 and 2 alone accounting for 65% of cases. The three dominant forms of the syndrome are inherited in an autosomal dominant manner, with mutations in KCNQ1, KCNH2 and SCN5A implicated in the pathogenesis of LQTS 1, 2 and 3, respectively. Prolongation of the QT interval is key to diagnosis, although it may periodically be absent in the same patient. The risk of arrhythmia is proportional to the degree of prolongation of the QT interval, and thus the duration of phase 2 of the action potential when there is risk of EAD and arrhythmia (Figure 3). While the diagnosis of LQTS can be unproblematic, it is often challenging, and the Schwartz criteria (Table 1) can be used to aid diagnosis: a diagnosis of LQTS is likely if the score is 4 or more, probable it if is 2e3 and unlikely if it is 1.1
Diagnosis can be further aided by adrenaline (epinephrine) and exercise testing in the 4th minute of recovery; both aim to identify paradoxical prolongation of the QT interval as the heart rate increases. Implantable cardioverter-defibrillators (ICDs) are recommended for all cardiac arrest survivors. b-Adrenoceptor blockers are recommended for patients with prolonged QTc and syncope, or genetically proven mutations even with a normal QTc. Nadolol has the strongest evidence base but propranolol can be used if nadolol is not available. If patients have further syncopal events or torsades de pointes while on b-blockers, left cardiac sympathetic denervation and/or an ICD should be strongly considered. It is important to remember that many medications can cause prolongation of the QT interval. These should therefore be excluded before a diagnosis of LQTS is made. In addition, they should be avoided in patients with an LQTS diagnosis. Relevant information can be obtained from national societies or online (e.g. www.qtdrugs.org). Family cascade screening is imperative using genetic testing in gene-positive index cases, but clinical phenotypic testing is valuable even if gene testing is negative.
Prolongation of phase 2, and thus the vulnerable area for EADs, in LQTS +50
Brugada syndrome Brugada syndrome is characterized by coved ST elevation (2 mm) in at least one right precordial lead (V1 or V2) placed at the fourth or higher intercostal space e the type 1 pattern. Type 2 and 3 forms have been described but are of clinical significance only when pharmacological provocation results in a type 1 appearance. The diagnosis relies on a type 1 electrocardiogram (ECG) plus one of syncope, nocturnal agonal respiration, similar ECG changes in family members or a family history of sudden cardiac death. The Shanghai score has been proposed to aid diagnosis based upon these variables in patients who are asymptomatic with a provoked type 1 Brugada ECG pattern.2 There is a male:female preponderance of about 9:1 and an increased prevalence in the South/South-East Asian population (See Figure 4). In contrast to LQTS, the genetic basis of Brugada syndrome is not monogeneic but highly complex. Numerous genes have been
1 2
mV
0
0
3
–50
4 –100 Figure 2
Figure 3 A 12-lead ECG from a patient with LQTS 1 (QTc ¼ 520 ms).
MEDICINE 46:10
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Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
these should be treated aggressively in patients with the condition. The type 1 ECG can also be brought on by certain medications or mimicked by others; online resources (e.g. www. brugadadrugs.org) list medications that should be avoided in patients with Brugada syndrome. Most patients with Brugada syndrome have a low risk of sudden cardiac death (<1%/year). There is no established medical treatment for Brugada syndrome, although isoprenaline and quinidine have been used with some success in patients with electrical storm in the acute and subacute phases. To date, only ICDs have been shown to prevent sudden death in Brugada syndrome, and they are recommended in cardiac arrest survivors. Otherwise, risk stratification for primary prevention devices is challenging. Syncope in a patient with a spontaneous type 1 ECG conveys the highest risk of ventricular fibrillation (VF), whereas asymptomatic patients with induced type 1 ECGs have a low risk of VF. Decisions must be taken on an individual basis and are often informed by patient choice, particularly if there has been a death in the family. The role of electrophysiological studies in risk-stratifying patients is highly controversial.3 Epicardial catheter ablation of the right ventricular outflow tract is an exciting evolving management strategy that has been shown to eliminate the type 1 Brugada ECG pattern and terminate VF storms.
Schwartz criteria for diagnosing LQTS Criterion ECG findings (no QT-prolonging drugs) QTc >480 ms QTc 460e479 ms QTc 450e459 ms in men Torsades de pointes T wave alternans Notched T wave in three leads Bradycardia Clinical history Syncope with stress Syncope without stress Congenital deafness Family history Family members with score >3 Unexplained death in immediate family <30 years of age
Score
3 2 1 2 1 1 0.5 2 1 0.5 1 0.5
Table 1
implicated in the disease, particularly mutations in SCN5A. The genes that cause the condition are inherited in an autosomal dominant manner, but severity of phenotype does not appear to be inherited. It is now understood that abnormalities in phenotypic expression are the result of numerous genetic mutations that conflate in an additive genetic effect. The pathophysiological basis of Brugada syndrome is debated. Increasing pathological and imaging data suggest that structural right ventricular heart disease is common. As such, Brugada syndrome has also been regarded as a subcategory of arrhythmogenic right ventricular cardiomyopathy, as opposed to a pure channelopathy. In family members of patients with confirmed Brugada syndrome who have a normal ECG, pharmacological provocation using a sodium channel blocker (e.g. ajmaline, flecainide) can be performed as this can unmask a type 1 Brugada ECG pattern to aid diagnosis. A type 1 ECG can also be provoked by fevers, and
Miscellaneous conditions Several other rare channelopathies can result in sudden death. These include short QT syndrome, early repolarization syndrome and catcholaminergic polymorphic ventricular tachycardia: Short QT syndrome is very rare. Families typically have a QTc <320 ms and abnormal T waves. Inheritance is autosomal dominant with three genes implicated. ICDs are used to prevent sudden death in these patients. Early repolarization syndrome describes an ECG abnormality found in a proportion of survivors of sudden cardiac death with structurally normal hearts. The ECG shows elevation of the J point. Unfortunately, this is a common finding in the general population, and ECG characteristics
Figure 4 A 12-lead ECG from a patient with a type 1 Brugada pattern in leads V1, HV1 and HV2 (‘high’ V1 and V2 leads placed in the second intercostal spaces, and shown on this ECG instead of V5 and V6, respectively).
MEDICINE 46:10
620
Ó 2018 Elsevier Ltd. All rights reserved.
CARDIAC GENETICS
Gene testing should be targeted, seeking advice from clinical geneticists before testing. Complex decisions should be taken in the context of the multidisciplinary team, with input from an expert in specialist inherited cardiac conditions A
that prophylactically identify patients at high risk remain to be determined. Catcholaminergic polymorphic ventricular tachycardia presents in children, often on exertion, and is characterized by exertional bi-directional ventricular tachycardia that degenerates into VF. The resting ECG is normal. Nadolol, ICDs and cervical sympathectomy have therapeutic roles.
KEY REFERENCES 1 Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88: 782e4. 2 Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge. J Arrhythm 2016; 32: 315e39. 3 Paul M, Gerss J, Schulze-Barh E, et al. Role of programmed ventricular stimulation in patients with Brugada syndrome: a metaanalysis of worldwide published data. Eur Heart J 2007; 28: 2126e33.
General clinical points for all channelopathies Syncope in children and young adults, particularly on exertion, demands investigation including an ECG. Channelopathies should be considered and diagnoses actively sought in patients with aborted sudden cardiac death who have structurally normal hearts and normal coronary arteries. Clinical consultations should consider diagnosis, risk stratification, need for gene testing and family screening.
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. What is the next best step? A. Reassurance B. Send the patient for genetic testing C. Take a more thorough history D. Insert an implantable cardioverter-defibrillator E. Start b-adrenoceptor blocker therapy
Question 1 A 14-year-old girl presented with an episode of collapse and syncope on exertion. She was not taking any medications. Clinical examination was normal. Investigations ECG showed sinus rhythm and a prolonged QTc of 490 ms Magnetic resonance scan of the heart was normal
Question 3 A 25-year-old woman presented with an out-of-hospital ventricular fibrillation arrest. After a week on intensive care, she made a full neurological recovery.
What is the most important next step in her arrhythmia management? A. Take a family history B. Start nadolol therapy C. Perform an exercise or adrenaline test D. Insert an implantable cardioverter-defibrillator E. Discharge the girl
Investigations Continuous ECG monitoring was normal ECGs with exercise, ajmaline and adrenaline challenge were all normal Magnetic resonance scan of the heart was normal Coronary angiogram was normal
Question 2 A 19-year-old man presented for reassurance after the sudden unexpected death of his father at age 38 years. He has had seizures in the past. Clinical examination was normal.
What is the best next step for this patient prior to hospital discharge? A. Prescribe amiodarone B. Refer for urgent genetic testing C. Implant a loop recorder (ILR) D. Insert a transvenous implantable cardioverter-defibrillator (ICD) E. Insert a subcutaneous ICD
Investigations Resting ECG was normal and showed sinus rhythm An ajmaline challenge ECG showed a type 1 Brugada pattern
MEDICINE 46:10
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Ó 2018 Elsevier Ltd. All rights reserved.