Warning Symptoms and Family History in Children and Young Adults with Sudden Cardiac Arrest

Discussion

The prevalence of warning signs and symptoms in children and young adults with occult cardiovascular disease is poorly understood. As demonstrated in this study, an important proportion of children and young adults with cardiovascular disorders that go on to experience SCA may have warning symptoms or a significant family history of premature cardiovascular disease that could be identified through appropriate screening.

Routine well-child visits are universally conducted in the United States and focus on a continuum of disease detection, disease prevention, health promotion, and anticipatory guidance throughout childhood and adolescence.¹⁵ Nevertheless, current standards in medical education lack any substantial emphasis in detecting cardiovascular warning symptoms in children, and the recommended cardiac evaluation in children is often limited to the presence of cyanosis, chest pain, asymmetric pulses, or a detectable murmur.¹⁵

A greater emphasis has been placed on the cardiovascular evaluation of children and young adults participating in competitive athletics. The American College of Cardiology states that the primary objective of the preparticipation evaluation of athletes is the detection of silent cardiovascular abnormalities that predispose to SCD.¹⁶ In 1996 the AHA provided consensus recommendations for the preparticipation cardiovascular evaluation of athletes, which includes 12 elements of a personal history, family history, and the physical examination.^9,17 These consensus recommendations were reaffirmed in 2007. Unfortunately, more than a decade later, use of a comprehensive history questionnaire in the cardiovascular screening of athletes has not been adopted widely into practice by primary care providers. In the United States, 35% of states allow nonphysician examiners with little cardiovascular training to perform a preparticipation evaluation, and only 81% of states have adequate questionnaires based on the AHA recommendations.¹²

Despite longstanding recommendations for a history- and physical-based preparticipation evaluation, there are no outcomes-based studies that demonstrate that the traditional preparticipation evaluation is effective in preventing or detecting athletes at risk for sudden death. A 1996 US study reviewed sudden deaths in 158 trained athletes, 134 of whom were though to have suffered SCA of a cardiovascular cause.⁴ Only 3% of athletes who suffered SCA were suspected of having cardiovascular disease, and only one athlete with a specific cardiac anomaly was correctly identified by a preparticipation screen. Although the details and adequacy of the preparticipation evaluations performed were not reported, the authors summarized that preparticipation screening seemed to be of limited value for the identification of underlying cardiovascular abnormalities.⁴

A significant challenge to screening is that asymptomatic, apparently healthy children and young adults may harbor unsuspected cardiovascular disease.^18,19 Sudden death is the first manifestation of a cardiac disorder in 50% to 80% of young athletes.^4⇓⇓–7 Only 21% of athletes who died from hypertrophic cardiomyopathy⁴ and 44% of athletes who died of an anomalous coronary artery⁶ had any signs or symptoms of cardiovascular disease in the years before their death. Sudden death also was found to be the sentinel cardiovascular event in 80% to 90% of autopsy-negative sudden unexplained death.^7,20

However, symptoms in children and young adults with primary structural or electrical cardiac abnormalities may, in fact, be relatively common but be misinterpreted or disregarded by medical providers. A 1996 report summarized 9 publications detailing 469 sudden deaths from cardiac causes in young persons.²¹ These studies collectively reported preceding symptoms of dizziness, chest pain, syncope, palpitations, dyspnea, and a family history of sudden death from a cardiac cause in 25% to 61% in their study populations.²¹ Wisten and Messner¹⁸ investigated symptoms in a Swedish cohort of 15 to 35 year olds who had suffered SCD and reported that 92 of 162 individuals with SCD (57%) had preceding symptoms that often were misinterpreted. In this study, 72% of children were reported to have at least one cardiovascular symptom before SCA. Even less information is known about the prevalence of a family history of cardiovascular disease in children that go on to experience SCA. In this study, 40% of the study population reported at least one significant family history component present before their child's SCA.

The relative infrequency of SCA in children and young adults makes prospective study of warning symptoms very challenging. This study attempted to examine a large cohort of families affected by SCA. However, the limitations of this study should be recognized in the interpretation of the results. A survey of families and parents who have lost a child to SCA has a high potential for recall and reporting bias when inquiring about the presence of warning symptoms before SCA. Thus, the reported presence of warning symptoms before SCA in this study may be overestimated. The reported duration of time between initial symptom onset and SCA also may be overestimated. This study was not designed to compare differences among the etiologies reported, and it is possible that different causes of SCA may affect the likelihood of symptoms. There was no control group without SCA for the comparison of symptom and family history frequency, and the study was not designed to determine the sensitivity, specificity, or positive and negative predictive values of each symptom or family history element. It is unknown if asking a general population of children and young adults questions about subjective cardiovascular symptoms such as chest pain and lightheadedness will yield an acceptable accuracy to identify children at elevated risk for SCA or if these symptoms are just too common in the pediatric population to make it a valuable screening question.

However, the number of victims with multiple episodes of an objective warning event such as syncope or unexplained seizure activity that went undetected as cardiovascular disease before their death is alarming. Syncope and unexplained seizure activity represent distinct events in a person's medical history and are therefore less likely to be affected by recall bias. The reporting of a family history of cardiovascular disease is also less likely to be inaccurate, although many of the families may have learned of their family history of cardiovascular disease after their child's event. Based on the results of this study, if physicians at well-child and preparticipation visits emphasize only 3 objective historical features (history of syncope, history of unexplained seizure activity, and a family history of sudden death caused by heart disease at an age younger than 50 years), approximately one third of children and young adults with cardiovascular disorders at elevated risk for SCA may be detected, assuming an appropriate diagnostic evaluation then is conducted.

Syncope in the young usually represents neurocardiogenic syncope, also known as vasovagal syncope, and often is triggered by specific events such as fear, pain, excitement, blood draws, or prolonged standing.²² Premonitory symptoms before collapse are common in vasovagal syncope and include lightheadedness, dizziness, diaphoresis, nausea, and tunnel vision. In contrast, individuals with syncope from a cardiac disorder at risk for SCA usually have an abrupt collapse without warning because of the onset of a potentially lethal ventricular arrhythmia.

The diagnosis of vasovagal syncope is made by a clinical history consistent with neurocardiogenic syncope, a normal physical examination, and a normal 12-lead electrocardiogram (ECG) to exclude findings suggestive of underlying cardiac disorders, such as ion channel disorders or cardiomyopathies. Routine testing with ECG is recommended during the initial evaluation of any child or young adult with syncope. Ritter et al²³ reviewed the records of 480 pediatric patients (median age, 13 years) who presented with syncope. A cardiac etiology for syncope was identified in 22 patients (5%), including long QT syndrome (n = 14), arrhythmias (n = 6), and cardiomyopathies (n = 2). An abnormal history (exercise-induced syncope or family history of sudden death), physical examination, or ECG identified 21 of the 22 patients with a cardiac cause of syncope (96% sensitivity; 99% negative predictive value).²³ If the history and physical examination are typical for neurocardiogenic syncope and the ECG is normal, further testing generally is not needed.

Syncope occurring during exercise is an ominous sign and warrants a high index of suspicion for underlying cardiac disease. In a review of 474 athletes with a history of syncope or near-syncope found during preparticipation screening, 33% with syncope that occurred during exercise were found to have a structural cardiac disease known to cause SCD.²⁴ The diagnostic workup of exertional syncope usually is performed in consultation with a cardiologist and should include an ECG, echocardiogram, stress ECG, and possibly advanced cardiac imaging (such as cardiac magnetic resonance imaging or computed tomography) to rule out rare structural abnormalities such as arrhythmogenic right ventricular cardiomyopathy or congenital coronary artery anomalies.

Seizures can be difficult to distinguish from syncope and thus should be part of the differential diagnosis. It should be noted that myoclonic movements caused by cerebral hypoperfusion can mimic true seizures. The clinical difference between the 2 is that if cerebral hypoperfusion is causing the myoclonic movements, the individual usually collapses first and then develops involuntary body movements seconds later, whereas with a true seizure the myoclonic movements would begin concurrently with the loss of postural tone and consciousness.²⁵ SCA is commonly mistaken for a seizure.²⁶ Brief seizure-like activity or involuntary myoclonic jerks are reported in approximately 50% of young athletes with SCA.^27,28 Any patient with unexplained seizure activity should have a cardiovascular workup, including a 12-lead ECG and an echocardiogram at a minimum.

Postmortem genetic screening is also important in the identification of the cause of SCA and of other at-risk family members with the same cardiac condition. In studies performing postmortem genetic testing (so-called “molecular autopsy”) in cases of autopsy-negative sudden unexplained death, more than one third of cases were found to have a pathogenic cardiac ion channel mutation.^20,29 Similarly, in this study, a cause of SCA was identified by postmortem genetic testing in 45% of cases with autopsy-negative sudden unexplained death. A definite diagnosis of SCA based on genetic testing allows for possible treatment of and improved risk reduction in family members. Further research is needed to better understand the prevalence of potential cardiovascular warning symptoms in a general pediatric population and to determine the questions with the highest likelihood of identifying individuals with underlying cardiac conditions that predispose to sudden death.