Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in children

INTRODUCTION — Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in children and adolescents are relatively rare. However, because these are unexpected, devastating conditions, concerted efforts have been made to continue to find evidence-based strategies to reduce or prevent these events.

The incidence, etiology, and prodromal signs of SCA/SCD in children and adolescents will be reviewed here. In addition, the role of screening to prevent pediatric SCA/SCD and the approach to evaluating survivors of SCA and victims of SCD will also be discussed.

The management of children with cardiopulmonary arrest is discussed separately. (See "Pediatric advanced life support (PALS)" and "Technique of defibrillation and cardioversion in children (including automated external defibrillation)".)

EPIDEMIOLOGY — The reported incidence of SCA/SCD in children and young adults ranges from 0.5 to 2.5 per 100,000 person-years [1-11]. In the United States, the Centers for Disease Control and Prevention estimates that approximately 1500 people under 25 years of age die each year of SCD [12]. The mortality rate for children presenting to the emergency department after SCD is approximately 90 percent [9]. Most studies have shown a bimodal age distribution, with higher incidence rates in infancy and adolescence/young adulthood [6,8,13]. In one report, the male to female ratio was 1.7:1 [9].

In a population-based study from the state of Washington (1980 to 2009), the overall incidence of SCA among people aged 0 to 35 years was 2.28 per 100,000 person-years [8]. Incidence rates and survival rates varied according to age:

●0 to 2 years – 2.1 cases per 100,000 person-years; 27 percent survival

●3 to 13 years – 0.61 cases per 100,000 person-years; 40 percent survival

●14 to 25 years – 1.44 cases per 100,000 person-years; 37 percent survival

Overall survival improved considerably over the course of the study period (from 13 percent in the 1980s to 40 percent in the 2000s), which the authors attributed to improvements in the community-based emergency medical services and changes in resuscitation protocols.

In a prospective study carried out in Australia and New Zealand from 2010 to 2012, the annual incidence of SCD among people age 1 to 35 years was 1.3 cases per 100,000; 72 percent of cases involved boys or young men [6].

In a report using data from the National Center for the Review and Prevention of Child Deaths database (2005 to 2009), 1098 cases of pediatric cardiovascular deaths were identified [13]. In this cohort, there was a male predominance (58 percent); 71 percent were White, 22 percent were Black, and 20 percent were Hispanic.

Approximately one-half to three-quarters of victims of SCA/SCD do not have antecedent symptoms prior to the event; however, a significant minority of patients do have antecedent symptoms (see 'Warning signs' below). In a population-based study from Denmark, antecedent symptoms were noted days to years prior to SCD in 45 percent of cases [7]. The most common antecedent symptoms were syncope, dyspnea, and seizure. Two-thirds of the SCD cases in this study had no previous medical history, whereas 18 percent had known cardiac disease.

Whether exercise and athletic activity increase the risk of SCA/SCD is uncertain [14]. In the prospective study from Australia and New Zealand, most cases of SCD occurred while the person was sleeping (38 percent) or at rest (27 percent), whereas SCD during exercise (11 percent) or after exercise (4 percent) was relatively uncommon [6]. In the previously described study from Washington state, among the SCA cases in which the relationship with exercise could be determined (n = 302), 25 percent occurred within one hour of exercise [8].

ETIOLOGY — In many cases of SCA/SCD, the cause is not identified. In a prospective study of 490 cases of SCD in children and young adults, 40 percent were unexplained [6].

When an etiology is identified, common causes include [6,8,15,16]:

●Primary arrhythmia/channelopathy (22 percent), including:

•Long QT syndrome (see "Congenital long QT syndrome: Epidemiology and clinical manifestations", section on 'Clinical manifestations')

•Wolff-Parkinson-White syndrome (see "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis")

•Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation")

•Short QT syndrome (see "Short QT syndrome")

•Catecholaminergic polymorphic ventricular tachycardia (see "Catecholaminergic polymorphic ventricular tachycardia")

●Myocarditis (7 to 35 percent). (See "Clinical manifestations and diagnosis of myocarditis in children".)

●Cardiomyopathy (16 to 20 percent), including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction cardiomyopathy, and arrhythmogenic cardiomyopathy. (See "Definition and classification of the cardiomyopathies".)

●Congenital heart disease (CHD; 15 percent), such as tetralogy of Fallot, hypoplastic left heart syndrome, and transposition of the great arteries. (See "Cardiac causes of cyanosis in the newborn" and "Identifying newborns with critical congenital heart disease".)

●Premature coronary artery disease was reported in some case series that included young adults (ie, 30 to 35 years old); however, this is an uncommon cause of SCA/SCD in patients <25 years old.

●Other cardiac disorders (4 to 8 percent), including coronary arteritis, anomalous origin of coronary arteries, aortic dissection, pulmonary hypertension, and mitral valve prolapse; however, the relationship between mitral valve prolapse and SCD is uncertain. (See "Congenital and pediatric coronary artery abnormalities" and "Mitral valve prolapse: Overview of complications and their management", section on 'Ventricular arrhythmias and sudden cardiac death'.)

●Unspecified cardiac disease (7 percent).

Causes of SCA/SCD vary somewhat by age [8]. In young children (<2 years old), CHD is a major cause, while primary arrhythmia and myocarditis are less common. In adolescents and young adults, primary arrhythmia, cardiomyopathy, and myocarditis are more common and CHD is a less common cause of SCA/SCD. Premature atherosclerotic coronary artery disease is an uncommon cause of SCA/SCD in patients <25 years old. However, children and adolescents can have coronary disease from Kawasaki disease or anomalous origin of the coronary arteries, which may cause SCD. (See "Cardiovascular sequelae of Kawasaki disease: Management and prognosis" and "Congenital and pediatric coronary artery abnormalities".)

The etiology of SCA/SCD in young competitive athletes may differ somewhat from the general population. This is discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Etiology of sudden death'.)

WARNING SIGNS

Symptoms — Although SCA/SCD is often the initial presenting event, retrospective studies have shown that warning signs or symptoms (eg, chest pain, fatigue, and syncope/lightheadedness) were noted by one-quarter to more than one-half of affected individuals prior to SCA/SCD [15,17,18]. The most common symptoms were chest pain and syncope/presyncope. Other symptoms included dizziness, palpitations, or dyspnea. It is important to note that these are nonspecific symptoms that occur commonly in the general pediatric and adolescent population. Thus, whether they truly are warning signs remains uncertain. None of these studies included a control group.

In addition to preceding symptoms, many patients (25 to 61 percent) who experience SCA/SCD have a family history of premature unexpected death in other family members [17,18].

In a study based on surveys completed by parents of 86 children and young adults (<30 years old) with SCA, at least one prior cardiovascular symptom was reported by 70 percent of respondents [18]. Fatigue (44 percent) and near syncope/lightheadedness (30 percent) were the most common complaints, with onset of symptoms on average 30 months prior to SCA. In addition, 24 percent of SCA victims had one or more events (average 2.6) of syncope or unexplained seizure-like activity that remained undiagnosed before SCA. In approximately 40 percent of cases, the symptom was brought to the attention of the child's clinician, and 27 percent of families reported a history of a family member who had suffered SCD before 50 years of age.

Differential diagnosis — The prodromal symptoms described above are nonspecific and noncardiac causes should also be considered. The distinction can often be made based upon the presentation, though sometimes additional tests are necessary to exclude underlying cardiac disease.

●Syncope – In children, the most likely cause of syncope or presyncope is neurocardiogenic syncope, also referred to as vasovagal syncope. Vasovagal syncope is often triggered by pain or fear and is commonly accompanied by premonitory symptoms before collapse, such as lightheadedness, dizziness, diaphoresis, nausea, and tunnel vision. In contrast, syncope associated with arrhythmia generally occurs without warning or during exercise, or is associated with chest pain or palpitations.

Other less common causes of pediatric syncope include migraine headaches, seizures, and brain tumors. These conditions, like vasovagal syncope, are associated with prodromal symptoms or, in the case of seizures, a postictal state and incontinence. The causes and evaluation of pediatric syncope are discussed separately. (See "Causes of syncope in children and adolescents" and "Emergency evaluation of syncope in children and adolescents", section on 'Evaluation'.)

●Chest pain – Chest pain is a common finding in children and is generally due to musculoskeletal conditions, such as costochondritis or trauma. In contrast, cardiac disease is an uncommon cause of chest pain [19]. Patients with cardiomyopathies or abnormalities of the coronary arteries or aorta may present with chest pain, but chest pain is very uncommon in patients with primary electrical disorders. Cardiac disease is more likely if chest pain occurs during exertion, is recurrent, or is accompanied by palpitations or syncope. The approach to evaluation of chest pain in children is discussed separately. (See "Nontraumatic chest pain in children and adolescents: Approach and initial management".)

●Respiratory difficulties/dyspnea on exertion – Common noncardiac causes of respiratory symptoms in children include asthma, bronchiolitis, and pneumonia. Patients with cardiomyopathy, structural heart disease, and arrhythmia may present with dyspnea on exertion. Exercise-induced bronchospasm associated with cardiomyopathy is generally unresponsive to bronchodilator therapy, which differentiates it from asthma. Cardiopulmonary exercise testing can help differentiate cardiac from pulmonary limitation of functional capacity, particularly when the cause is unclear from the history and physical examination. Causes of respiratory distress and the assessment of children who present with respiratory difficulties are discussed in greater detail separately. (See "Causes of acute respiratory distress in children".)

Electrocardiogram findings — Electrocardiograms (ECGs) are obtained in children for a variety of reasons (evaluation of concerning symptoms, screening prior to starting certain medications). A high-quality 12-lead ECG, with standard paper speed and amplitudes, is necessary to make accurate measurements and avoid artifact in ECG interpretation. It is important to recognize potentially pathologic ECG findings and distinguish them from findings that are generally benign. Though the distinction can often be made by the non-cardiologist, consultation with a pediatric cardiologist may be warranted.

ECG findings that warrant further evaluation (which, depending on the finding, may include review of the history and physical examination, echocardiography, ambulatory ECG monitoring, implantable loop recorder, stress testing, cardiac magnetic resonance imaging, and/or or genetic testing) include the following [20]:

●Prominent/abnormal Q waves – Q waves >3 mm in depth and/or >40 ms duration in at least two leads are characteristic findings for hypertrophic cardiomyopathy (waveform 1). (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Electrocardiography' and "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Electrocardiography'.)

●Wide QRS – Conduction delay with a QRS duration >90 ms in children <4 years old, >100 ms in children 4 to 16 years old, and >120 ms in adults. (See "Left bundle branch block", section on 'ECG findings and diagnosis' and "Causes of wide QRS complex tachycardia in children", section on 'Supraventricular tachycardia'.)

●ST elevation/depression and T wave inversion – ST elevation >2 mm, ST depression >0.5 mm, and T wave inversions can be seen in patients with myocardial ischemia. T wave inversions in leads II, III, aVF, and the left precordial leads in combination may also be a sign of ventricular hypertrophy (waveform 1). (See "ECG tutorial: ST and T wave changes".)

●QT prolongation – For accurate assessment, the QT interval should be corrected for heart rate (QTc) by a standardized method. The computer-derived QTc should be confirmed or corrected manually. Prolonged QTc is suggestive of ion channel abnormalities either due to pathogenic gene variants or exposure to specific medications (waveform 2). (See "Congenital long QT syndrome: Diagnosis", section on '12-lead ECG' and "Short QT syndrome", section on 'Electrocardiographic findings' and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

●Delta waves – Delta wave (slurring of the initial QRS and a short PR interval [<120 ms]) is associated with Wolff-Parkinson-White syndrome (waveform 3). (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.)

Benign ECG findings (eg, sinus bradycardia, sinus arrhythmia, first-degree atrioventricular block, incomplete right bundle-branch block, early repolarization, and voltage criteria for left ventricular hypertrophy) are common in young people (especially trained athletes) and generally do not require further evaluation [20,21]. (See "Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances".)

DROWNING AND SUDDEN INFANT DEATH — SCD should be considered in cases of drowning and sudden unexplained infant death. In these settings, it is important to review the family history to see if there are any family members who died unexpectedly before the age of 50 years to ascertain if further testing (including genetic testing) is indicated. These issues are discussed in greater detail separately. (See "Drowning (submersion injuries)" and "Sudden unexpected infant death including SIDS: Initial management".)

PRIMARY PREVENTION OF SCD — Primary prevention aims to identify the at-risk individuals prior to SCA in order to intervene and prevent SCA and SCD.

Approach to screening — The optimal screening approach for primary prevention of SCD is uncertain. Based on the available data, we suggest screening for cardiac diseases associated with SCA and SCD using a detailed history and physical examination alone, without the routine use of additional testing such as electrocardiography (ECG), echocardiography, or stress testing. The one exception is universal pulse oximetry screening for critical congenital heart disease (CHD) in newborn infants, which is discussed separately. (See "Newborn screening for critical congenital heart disease using pulse oximetry".)

Key components of screening include [22]:

●Recognizing the warning signs and symptoms of SCA. (See 'Warning signs' above.)

●Obtaining a comprehensive and accurate history of any family member who died unexpectedly before the age of 50 years.

●Using standardized preparticipation athletic evaluation to minimize unnecessary variation. (See "Sports participation in children and adolescents: The preparticipation physical evaluation", section on 'Evaluation forms'.)

●Referring any patient or family with known or suspected cardiac disorders to a pediatric cardiac center for further evaluation, which may include ECG, echocardiography, cardiac magnetic resonance imaging, exercise testing, and genetic testing. (See "Suspected heart disease in infants and children: Criteria for referral".)

For competitive athletes, there is controversy as to the optimal approach for screening to prevent SCD and the available published guidelines differ somewhat, with some recommending against routine ECG screening [22-25], while other advocate for ECG screening in all young athletes [26,27]. Our approach is generally consistent with guidance from the American Heart Association and the American Academy of Pediatrics (AAP) [22-25]. Links to these and other society guidelines are provided separately. (See 'Society guideline links' below.).

Screening at routine health care visits — We suggest all children have regular cardiovascular assessments performed throughout childhood during routine health care visits [22,28]. We prefer universal screening rather than screening only during preparticipation sports assessments since many children do not participate in organized sports and would be omitted in a selective approach.

The assessment includes reviewing the history (including family history) and a detailed cardiovascular examination. We do not routinely obtain ECGs because it has poor sensitivity and specificity for identifying individuals at risk for SCD. False positives are common and false negatives can also occur. (See 'No role for routine ECG' below.)

Effective screening to identify children at risk for SCA requires repeat assessments throughout childhood since the causes of SCA and their clinical manifestations vary during childhood. (See 'Etiology' above.)

Important aspects of the history and physical examination may change over time in children at risk for SCA. For example, the family history may evolve (ie, a new family member may be affected) and symptoms of some cardiac conditions (eg, hypertrophic cardiomyopathy) may not present until adolescence.

History — The medical history focuses on the following [22,25]:

●When taking the patient's personal history, the clinician should ask about:

•Current or prior symptoms, such as exertion-induced chest pain, discomfort, tightness, or pressure; unexplained syncope or near-syncope; exercise-induced palpitation, dyspnea, or fatigue that is excessive and unexplained

•History of elevated systemic blood pressure

•Prior recognition of a heart murmur

•Any prior restriction from participation

•Any prior cardiac testing

●When assessing the family history, the clinician should ask about:

•Premature death attributable to heart disease (sudden or otherwise) before the age of 50 years in any relative

•Disability from heart disease in first- and second-degree relatives <50 years old

•Congenital deafness, syncope, seizures, unexplained car accidents, unexplained drownings

•Known genetic cardiac conditions in family members (eg, hypertrophic or dilated cardiomyopathy, long QT syndrome, other channelopathies or inherited arrhythmia syndromes, Marfan syndrome, or any other genetic cardiac condition)

Retrospective studies have shown that many children who experience SCA have prodromal warning signs and symptoms and/or have a family history of sudden and unexpected death of a family member before the age of 50 years. (See 'Warning signs' above.)

Physical examination — The physical examination includes measurement of blood pressure and resting heart rate, as well as cardiac auscultation to assess rate and rhythm of the heart and detect murmurs and other abnormal heart sounds. Physical findings suggestive of underlying cardiac disease include tachycardia, elevated blood pressure, and abnormal cardiovascular examination (eg, heart murmur, diminished femoral pulses), which are discussed in detail elsewhere. (See "Suspected heart disease in infants and children: Criteria for referral", section on 'Physical examination findings'.)

No role for routine ECG — In our practice, we do not routinely obtain ECGs unless concerns arise from the history or physical examination. However, the optimal approach to screening is uncertain and some have proposed routine ECG screening for this purpose, particularly in competitive athletes. ECG screening in young athletes is discussed in greater detail separately. (See "Sports participation in children and adolescents: The preparticipation physical evaluation", section on 'Noninvasive cardiovascular testing' and "Screening to prevent sudden cardiac death in competitive athletes".)

The sensitivity and specificity of ECG screening is highly variable and depends on the nature of the underlying cardiac condition and expertise of the clinician interpreting it [23]. For example, false-negative ECG results can occur in patients with coronary artery abnormalities since ECG is often normal in these patients. In addition, depending on the diagnostic threshold used, false-negative ECG screening may occur in up to 20 percent of patients with long QT syndrome. (See "Congenital and pediatric coronary artery abnormalities" and "Congenital long QT syndrome: Diagnosis", section on '12-lead ECG'.)

Similarly, false positives are very common in ECG screening, particularly in athletes. (See "Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances".)

Additional testing performed to evaluate false positives limits the cost-effectiveness of this approach [29,30].

The evidence evaluating the use of ECG as a screening tool for prevention of SCD comes largely from observational studies involving young athletes. It is difficult to draw firm conclusions from these studies due to the low incidence of SCD and differences in study populations and screening protocols used. The data on ECG screening in young athletes are discussed in detail separately. (See "Screening to prevent sudden cardiac death in competitive athletes", section on 'ECG screening (controversial)'.)

Studies in nonathletes are also limited. In a study of ECG screening in >7500 nonathletes between 14 and 35 years of age, patients were categorized as having benign ECG findings (which included entirely normal ECGs or only minor abnormalities unlikely to be of clinical significance [ie, sinus bradycardia, first-degree atrioventricular block, incomplete right bundle-branch block, early repolarization, and voltage criteria for left ventricular hypertrophy]) or potentially pathologic findings (including T wave inversion, ST-segment depression, pathologic Q waves, left or right atrial enlargement, left- or right-axis deviation, right ventricular hypertrophy, ventricular preexcitation, right bundle-branch block, left bundle-branch block, long QTc, short QTc, and Brugada-like pattern) [31]. Benign findings were noted in 49 percent, and potentially pathologic findings were noted in 22 percent. Approximately one-half of the individuals with potentially pathologic findings underwent echocardiography, which was normal in 84 percent. Only 2 percent of these patients (0.2 percent of the entire cohort) had findings consistent with a morphologically mild cardiomyopathy, and the remaining had incidental findings that would not affect management.

Preparticipation sports assessment — In the United States, a preparticipation sports assessment is the standard of care for children and adolescents who participate in an organized sport. The use of a standardized preparticipation assessment is endorsed by several major United States medical societies, including the AAP, to ensure that all the important aspects of the history and physical examination are addressed. (See "Sports participation in children and adolescents: The preparticipation physical evaluation", section on 'Evaluation forms'.)

The standardized evaluation includes a focused cardiovascular history, family history, and physical examination. The approach to the cardiovascular history in this setting is discussed in detail separately. (See "Sports participation in children and adolescents: The preparticipation physical evaluation", section on 'Cardiovascular history'.)

Further evaluation and referral — Pediatric patients with historical or physical findings that suggest cardiac disease should be referred to a pediatric cardiologist for further evaluation. The timing of referral is dependent on the clinical condition of the patient and the seriousness of the underlying diagnosis that may be suspected. Urgent referral or consultation with a pediatric cardiologist should occur in patients with or at risk for hemodynamic compromise and death due to suspected cardiac disease. (See "Suspected heart disease in infants and children: Criteria for referral", section on 'Timing of referral'.)

Patients with high-risk conditions — Strategies for primary prevention of SCD used in select pediatric patients with high-risk cardiac diseases include the following:

●For patients with dilated cardiomyopathy and left ventricular ejection fraction <35 percent despite maximal medical therapy, placement of an implantable cardioverter-defibrillator (ICD) may be considered. This is discussed separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Nonischemic dilated cardiomyopathy'.)

●For patients with hypertrophic cardiomyopathy with high-risk features, ICD placement may be considered. This is discussed separately. (See "Hypertrophic cardiomyopathy in children: Management and prognosis", section on 'Prevention of sudden cardiac death (ICD placement)'.)

●For patients with certain arrhythmia syndromes (eg, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia), beta blockers may be used for prevention of SCD, as discussed separately. (See "Congenital long QT syndrome: Treatment", section on 'Beta blockers' and "Catecholaminergic polymorphic ventricular tachycardia", section on 'Beta blockers'.)

SECONDARY PREVENTION — Secondary prevention strategies focus on treating children who have suffered SCA to improve the likelihood of survival after the event and to prevent subsequent episodes of SCA.

●Strategies to improve survival after SCA – It is unlikely that any primary prevention program alone will prevent all episodes of SCD. Therefore, it is important to improve the outcomes of children with SCA. We advocate community programs that increase public placement of automatic external defibrillators (AEDs) and teach effective bystander cardiopulmonary resuscitation (CPR) and AED use.

Poor outcome is related to prolonged periods without cardiac output, in part because effective CPR is not performed. In a study from the state of Washington, improved survival rate for children and young adults who suffered SCA was attributed, in part, to the publication of new resuscitative guidelines in 2005 and the presence of robust community-based emergency medical services [8]. In this study, the survival rate rose from 25 to 58 percent after the initiation of a single shock without rhythm reanalysis.

Both the American Heart Association and AAP support efforts to improve survival by early symptom recognition, the use of 9-1-1 emergency medical services, effective bystander CPR, and deployment and use of AEDs in the community [22,23]. In particular, developing and implementing CPR-AED programs within schools has saved the lives of both students and adults who have had SCA in the school setting [32]. (See "Prognosis and outcomes following sudden cardiac arrest in adults", section on 'Bystander CPR' and "Automated external defibrillators", section on 'AED allocation strategy'.)

●ICD placement – For survivors of SCA, secondary prevention may also involve placement of an ICD to prevent SCD from subsequent episodes of arrhythmia. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

EVALUATION

Survivors of SCA — Survivors of SCA should undergo a comprehensive workup under the direction of a pediatric cardiologist. The initial evaluation consists of a detailed history, family history, physical examination, electrocardiogram (ECG), and echocardiogram. Additional testing is guided by the results of the initial workup and may include:

●Ambulatory ECG monitoring

●Exercise stress test

●Cardiac magnetic resonance imaging

●Electrophysiologic testing, with possible intervention such as ablation if indicated

●Coronary computed tomography angiography

The decision to obtain genetic testing is based on initial test results, family history, and discretion of the treating cardiologist. First-degree relatives, including siblings and parents, should also be assessed. The studies that are done on first-degree relatives will depend upon the diagnosis of the affected individual.

In many survivors of SCA, an implantable cardioverter-defibrillator (ICD) is inserted to prevent SCD from recurrent episodes of arrhythmia. Use of ICDs in this setting is discussed in greater detail separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

Victims of SCD

Postmortem examination — When a child or adolescent dies unexpectedly, an assessment of the cardiac anatomy at the time of autopsy is critical. If the examining medical examiner/coroner does not have a level of comfort in the intricacies of cardiac anatomy, consultation should be sought. Histologic examination should be included to detect any finding consistent with cardiomyopathic conditions. Postmortem examination evaluates cardiac anatomy and histologic changes. Arrhythmia as a cause of death cannot be assessed on postmortem examination. Thus, if SCD remains unexplained despite an autopsy and toxicology (autopsy-negative sudden unexplained death), blood and tissue samples should be retained for genetic analysis [33].

Family history and evaluation of surviving relatives — A detailed family history should be obtained. Further assessment of first-degree relatives (ie, siblings and parents) is determined by the family history, autopsy results, and, in selected cases, genetic testing [34]. Clinical studies that may be useful in family investigation include electrocardiogram (ECG), echocardiogram, ambulatory rhythm monitoring, cardiac magnetic resonance imaging, exercise stress test, and/or electrophysiology testing. Screening relatives provides an opportunity to identify at-risk family members and initiate management strategies [34]. In one study, a comprehensive evaluation of surviving relatives (including resting and exercise ECG, echocardiography, and genetic testing) identified an inherited cardiac disease in 40 percent of cases [35]. Longitudinal cascade screening should be employed to assess cardiac status in at-risk, first-degree relatives. This may be done indefinitely, given that some patients do not manifest phenotypic evidence of disease until much later in life.

Genetic testing — A molecular autopsy (ie, postmortem genetic testing for channelopathies and cardiomyopathies) is sometimes useful in cases of SCD, particularly if the standard autopsy and family evaluation do not identify a cause [6,33,36-38]. Genetic testing may be targeted to identify mutations associated with long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (including mutations in the KCNQ1, KCNH2, SCN5A, and RYR2 genes) [34]. More comprehensive evaluation is possible with next-generation sequencing, which has been used in victims of SCD to detect putative pathogenic genetic variants in a broad spectrum of cardiomyopathy-, channelopathy-, and aortic disease-associated genes [6,39,40]. (See "Congenital long QT syndrome: Pathophysiology and genetics" and "Brugada syndrome: Epidemiology and pathogenesis", section on 'Genetics' and "Catecholaminergic polymorphic ventricular tachycardia", section on 'Genetics'.)

Genetic testing may also be performed in surviving family members if the history is suggestive of a heritable cause of SCD [35].

A genetic counselor is a key individual in helping the family deal with the complicated issues surrounding the unexpected death of the child and obtaining an accurate family pedigree that will aid in the diagnosis of the underlying cardiac defect.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in children".)

SUMMARY AND RECOMMENDATIONS

●Incidence – Pediatric sudden cardiac arrest (SCA) and sudden cardiac death (SCD) are relatively rare, with reported incidence of approximately 2 per 100,000 person-years. In the United States, survival following SCA among children and young adults has improved, with an estimated survival rate in the modern era of approximately 40 percent. (See 'Epidemiology' above.)

●Causes – Underlying cardiac diseases associated with SCA/SCD vary somewhat with age. For children <2 years, congenital heart disease (CHD) is the predominant cause of SCA. For older children and adolescents, other cardiac causes are more common, including primary arrhythmias, cardiomyopathy, and myocarditis. In many cases of SCA/SCD, the cause is not identified. (See 'Etiology' above.)

●Warning signs – Although SCA is often the initial presenting event, many children who experience SCA have prodromal warning signs and symptoms (eg, chest pain, fatigue, seizures, and syncope/lightheadedness) and/or have a family history of sudden and unexpected death of a family member before the age of 50 years. (See 'Warning signs' above.)

The prodromal signs and symptoms of SCA are nonspecific, and the differential diagnosis is broad. Other disorders that need to be distinguished from underlying cardiac disease include vasovagal syncope, migraine headaches, seizures, musculoskeletal chest pain, and asthma. (See 'Differential diagnosis' above.)

●Prevention – Preventive strategies to reduce SCD include primary screening to identify and intervene in at-risk individuals, as well as secondary prevention efforts to facilitate successful resuscitation and improve long-term outcomes of survivors of SCA.

•Primary prevention – We suggest screening for cardiac diseases associated with SCA and SCD using a detailed history and physical examination alone, rather than routinely using electrocardiography (ECG) for this purpose (Grade 2C). (See 'Approach to screening' above.)

During routine health visits, the following aspects of the history should be reviewed (see 'Screening at routine health care visits' above):

-History of syncope, near-syncope, or seizure

-Exercise-induced chest pain or shortness of breath

-History of sudden unexpected, unexplained death in a family member before 50 years of age

-Family history of cardiac disease associated with sudden death (eg, long QT syndrome)

Routine physical examination should include (see "The pediatric physical examination: Chest and abdomen", section on 'Heart' and "Approach to the infant or child with a cardiac murmur", section on 'Auscultation of heart sounds and murmurs'):

-Measurement of blood pressure and resting heart rate

-Cardiac auscultation to assess rate and rhythm of the heart and detect murmurs and other abnormal heart sounds

Children and adolescents who participate in an organized sport should undergo a standardized preparticipation evaluation that includes a cardiovascular assessment. (See "Sports participation in children and adolescents: The preparticipation physical evaluation".)

Patients with historical or physical examination findings suggestive of an underlying cardiac disorder should undergo further evaluation (including ECG) and/or referred to a cardiac specialist with pediatric expertise. (See 'Further evaluation and referral' above and "Suspected heart disease in infants and children: Criteria for referral".)

•Secondary prevention – Secondary prevention strategies aim to improve the outcomes of children who suffer SCA. Such efforts include community programs to increase public placement of automatic external defibrillators (AEDs) and to teach effective bystander cardiopulmonary resuscitation (CPR) and AED use. (See 'Secondary prevention' above.)

In addition, for survivors of SCA, secondary prevention may involve placement of an implantable cardioverter-defibrillator (ICD) to prevent SCD from subsequent episodes of arrhythmia. This issue is discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

●Evaluation for the underlying cause

•Survivors of SCA – Survivors of SCA should undergo a comprehensive evaluation aimed at identifying and treating the underlying cardiac condition. The initial assessment includes a detailed history, family history, physical examination, ECG, and echocardiogram. Additional testing is guided by the results of the initial workup and may include ambulatory ECG monitoring, exercise stress test, cardiac magnetic resonance imaging, electrophysiologic testing, and/or genetic testing. (See 'Survivors of SCA' above.)

•Victims of SCD – When a child or adolescent dies unexpectedly, an autopsy that includes a full assessment of cardiac anatomy and histology should be performed. If a cardiac anatomic explanation for the SCD episode is not found, evaluation should include family screening and genetic testing. (See 'Victims of SCD' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stuart Berger, MD, and John L Jefferies, MD, MPH, FACC, FAHA, who contributed to earlier versions of this topic review.