The investigation of the aetiology of sudden cardiac arrest or death in a young person combines features of a traditional clinical medical examination with those of forensic medicine. Nuances of the immediate peri-event history, when available, can be paramount. New genetic tools have greatly improved the yield of such investigations, but they must be carefully interpreted by genetic specialists. The approach to surviving patients, their family members, and to family members of non-survivors is best achieved in a structured programme that includes all appropriate specialists and support personnel. As an example, this may include all appropriate paediatric and internal medicine specialists, a geneticist, a genetic counsellor, a clinical psychologist, nurse specialist(s), and a programme coordinator. This family-centred strategy affords the patient, if surviving, and all family members the necessary emotional and medical support while at the same time providing the necessary diagnostic and therapeutic approaches.

Paediatric exercise stress testing has historically been used to assess the functional status of patients after repair of CHDs and to assess the efficacy of medical or device therapy in patients with arrhythmias. Exercise stress testing is one of very few hospital- or clinic-based tests that can assess the response of the cardiopulmonary system in an environment that simulates the body’s response to vigorous play and competitive sport. Exercise stress testing is therefore a useful modality in the assessment of child and athletes at risk for sudden cardiac death. The author discusses some cardiovascular maladies that can cause sudden cardiac death by utilising case illustrations as a learning tool.

The molecular millennium has bestowed clinicians and researchers with the essential tools to identify the underlying genetic substrates for thousands of genetic disorders, most of which are rare and follow Mendelian inheritance patterns. The genetic basis of potentially lethal and heritable cardiomyopathies and cardiac channelopathies has been identified and are now better understood. Genetic testing for several of these heritable conditions has made its transition from discovery through translation and have been commercially available clinical tests for over a decade. Now that clinical genetic testing is available more readily and delivers a disease-specific impact across the triad of medicine – diagnostic, prognostic, and therapeutic – it is important for the community of cardiologists to not only be familiar with the language of genomic medicine but to also be wiser users and even wiser interpreters of genetic testing so that wise decisions can be rendered for those patients and their families being evaluated with respect to the presence or absence of one of these potentially lethal yet highly treatable genetic disorders. The purpose of this review is to provide the reader with a foundational understanding of genetic testing in clinical cardiology. Here, we will present some benefits of genetic testing: indications for either post-mortem genetic testing for the major cardiomyopathies and channelopathies or pre-mortem genetic testing among the decedent’s surviving relatives; the need for careful interpretation of genetic testing results; the importance of genetic counselling; and some points on the ethical and societal implications of genetic testing.

Hypertrophic cardiomyopathy is a common, inherited heart disease with a heterogeneous clinical presentation and natural history. Recently, advances in diagnosis and treatment options have been instrumental in decreasing the frequency of adverse clinical events; however, complete elimination of sudden cardiac death still remains an elusive gain. This article discusses several aspects of this condition in the young: epidemiology, clinical phenotypes, risk factors, prevention of sudden cardiac death, and risks of athletic participation.

Sudden unexpected cardiac deaths in approximately 20% of young athletes are due to acquired or congenital coronary artery abnormalities. Kawasaki disease is the leading cause for acquired coronary artery abnormalities, which can cause late coronary artery sequelae including aneurysms, stenosis, and thrombosis, leading to myocardial ischaemia and ventricular fibrillation. Patients with anomalous left coronary artery from the pulmonary artery can develop adequate collateral circulation from the right coronary artery in the newborn period, which remains asymptomatic only to manifest in adulthood with myocardial ischaemia, ventricular arrhythmias, and sudden death. Anomalous origin of coronary artery from the opposite sinus occurs in 0.7% of the young general population aged between 11 and 15 years. If the anomalous coronary artery courses between the pulmonary artery and the aorta, sudden cardiac death may occur during or shortly after vigorous exercise, especially in patients where the anomalous left coronary artery originates from the right sinus of Valsalva. Symptomatic patients with evidence of ischaemia should have surgical correction. No treatment is needed for asymptomatic patients with an anomalous right coronary artery from the left sinus of Valsalva. At present, there is no consensus regarding how to manage asymptomatic patients with anomalous left coronary artery from the right sinus of Valsalva and interarterial course. Myocardial bridging is commonly observed in cardiac catheterisation and it rarely causes exercise-induced coronary syndrome or cardiac death. In symptomatic patients, refractory or β-blocker treatment and surgical un-bridging may be considered.

Sudden death from aortic dissection of an ascending aortic aneurysm is an uncommon but important finding in all series of sudden death in young, apparently healthy athletes. Individuals at risk include those having any of a variety of conditions in which structural weakness of the ascending aorta predisposes to pathological dilation under prolonged periods of increased wall stress. These conditions include Marfan syndrome, Loeys–Dietz syndrome, bicuspid aortic valve, and the vascular form of Ehlers–Danlos syndrome. Diagnostic criteria, surveillance strategies, medical management, and surgical indications are discussed. Finally, the current recommendations for sports participation are provided.

Untreated congenital long QT syndrome may result in potentially lethal ventricular tachycardia. In the most common type, risk of such an event has been linked to exercise. This originally resulted in very restrictive guidelines for sports participation in affected individuals. Although the complex interactions of a specific genotype, modifying cofactors, and risk are only now being explored, scientific evidence based on clinical experience now suggests that in many instances such restrictive guidelines are unwarranted. In particular, patients with this condition who are compliant with β-blocker therapy and who have never had symptoms during exertion are now enjoying the benefits of athletic activity.

Since the sentinel description of exercise-triggered ventricular arrhythmias in 21 children, our recognition and understanding of catecholaminergic polymorphic ventricular tachycardia has improved substantially. A variety of treatments are now available, but reaching a diagnosis before cardiac arrest remains a challenge. Most cases are related to variants in the gene encoding for ryanodine receptor-2 (RyR2), which mediates calcium-induced calcium release. Up to half of cases remain genetically elusive. The condition is presently incurable, but one basic intervention, the universal administration of β-blockers, has improved survival. In the past, implantable cardioverter-defibrillators (ICDs) were frequently implanted, especially in those with a history of cardiac arrest. Treatment limitations include under-dosing and poor compliance with β-blockers, and potentially lethal ICD-related electrical storm. Newer therapies include flecainide and sympathetic ganglionectomy. Limited data have suggested that genotype may predict phenotype in catecholaminergic polymorphic ventricular tachycardia, including a higher risk of life-threatening cardiac events in subjects with variants in the C-terminus of ryanodine receptor-2 (RyR2). At present, international efforts are underway to better understand this condition through large prospective registries. The recent publication of gene therapy in an animal model of the recessive form of the disease highlights the importance of improving our understanding of the genetic underpinnings of the disease.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy characterised by ventricular arrhythmias and an increased risk of sudden cardiac death. Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnosis is based on criteria that take into account electrical and structural cardiac abnormalities, as well as mutation analysis. Appropriate pharmacological therapy and the prevention of sudden death with implantable defibrillators are important in the management of these patients. Exercise is considered an important environmental factor for the development and progression of the disease.

The Wolff–Parkinson–White pattern refers to the electrocardiographic appearance in sinus rhythm, wherein an accessory atrioventricular pathway abbreviates the P-R interval and causes a slurring of the QRS upslope – the “delta wave”. It may be asymptomatic or it may be associated with orthodromic reciprocating tachycardia; however, rarely, even in children, it is associated with sudden death due to ventricular fibrillation resulting from a rapid response by the accessory pathway to atrial fibrillation, which itself seems to result from orthodromic reciprocating tachycardia. Historically, patients at risk for sudden death were characterised by the presence of symptoms and a shortest pre- excited R-R interval during induced atrial fibrillation <250 ms. Owing to the relatively high prevalence of asymptomatic Wolff–Parkinson–White pattern and availability of catheter ablation, there has been a need to identify risk among asymptomatic patients. Recent guidelines recommend invasive evaluation for such patients where pre-excitation clearly does not disappear during exercise testing. This strategy has a high negative predictive value only. The accuracy of this approach is under continued investigation, especially in light of other considerations: Patients having intermittent pre-excitation, once thought to be at minimal risk may not be, and the role of isoproterenol in risk assessment.

The prevalence of sudden cardiac arrest after surgery for CHD is primarily related to the complexity of the congenital defect and the presence of residual defects, especially ventricular dysfunction. Among all causes of death in patients having CHD, about 19% lead to sudden mortality. The specific risk factors associated with the various congenital defects are poorly understood. The lone exception is tetralogy of Fallot, largely due to its high prevalence and the historically high post-operative survival rate. In tetralogy of Fallot, historical, haemodynamic, and electrical features contribute to risk, and electrophysiologic testing may be helpful, particularly to rule out risk. An implantable cardioverter–defibrillator is highly effective for secondary prevention in most forms of CHD, and future advances will improve its role in primary prevention.

The recreational use of illicit drugs remains an enormous and growing problem throughout the United States of America and around the world. Cocaine is most frequently thought of when considering the cardiovascular toxicity of illicit drugs. The association of cocaine use with sudden death due to myocardial ischaemia and infarction is well recognised, and this risk appears to be amplified by concomitant cigarette smoking and alcohol consumption. Like cocaine, amphetamine and its derivatives lead to indirect stimulation of the autonomic nervous system through the release of norepinephrine, dopamine, and serotonin in nerve terminals of the central and autonomic nervous systems. However, amphetamine lacks the ion channel-blocking properties of cocaine. Also similar to cocaine, coronary artery spasm may be induced in individuals with or without atherosclerotic disease and may lead to myocardial infarction. With the movement across the United States of America to legalise marijuana, or cannabis, for medicinal and recreational purposes, it is important to consider its potential deleterious effects. Marijuana has long been thought to have very few adverse effects with the exception of long-term dependence. There are, however, scattered reports of acute adverse events up to and including sudden death. These appear to be due to myocardial infarction. In conclusion, the incidence of sudden death associated with the use of these drugs varies from rare in the case of marijuana use to not infrequent with some drugs such as cocaine. It is important for care providers to recognise the potential for drug abuse when caring for a sudden cardiac arrest survivor.

Chronic physical training has been shown to produce multiple changes in the heart, resulting in the athlete’s heart phenotype. Some of the changes can make it difficult to discern athlete’s heart from true cardiac disease, most notably hypertrophic cardiomyopathy. Other diseases such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy may be difficult to rule in or out. In this article, the physiological cardiac changes of chronic athletic training are reviewed. A methodological approach using electrocardiography and echocardiography to differentiate between athlete’s heart and cardiac disease is proposed.

It has largely been accepted that pre-participation screening for student athletes is necessary, but there is still no consensus on the most effective and efficient ways to accomplish this. Most clinical strategies are based on retrospective case series. By applying the European Society of Cardiology and Seattle criteria, electrocardiography appears to afford the lowest false-positive rate for identifying potentially dangerous cardiac abnormalities in athletes. Prospective, randomised trials may help determine the most effective primary prevention. Normative data for age, gender, and ethnicity for screening tools need to be formulated to further reduce false-positive results. Targeted advanced screening aimed at the highest risk groups may be the most beneficial and cost-effective application of primary prevention.

The cardiovascular benefits of habitual exercise are well documented. In the current era, more of the population is exceeding the recommendations for physical activity as the popularity of endurance events increases. Recent data have proposed a U-shaped relationship between exercise intensity and cardiovascular outcomes. Regular participation in endurance activities has been shown to result in structural and functional changes in the heart. This re-modelling may be the substrate for cardiac dysfunction or arrhythmias. The risk of sudden cardiac death may also be elevated; however, in most cases of sudden cardiac death, the cause can be linked to an underlying cardiac pathology where exercise acted as the trigger for a lethal arrhythmia. This article serves to review whether excessive exercise may result in harm in some athletes.

Recent experiences with lay public cardiopulmonary resuscitation and use of ambulatory external defibrillators have been demonstrated to improve survival from out-of-hospital cardiac arrests from an abysmal 10% or less to as high as 30%. Though rare, sudden cardiac arrest in presumably healthy young people have been highly publicised over the last 25 years and have motivated the institution of school- and community-based programmes that facilitate first-responder resuscitation, including defibrillation. These efforts often begin at a grass roots level (usually parent-inspired advocacy groups) and through collaborative activities involving the schools, local businesses, and local administrative agencies are now having a meaningful impact in selected communities. The current focus of these activities is on school- and sports venue-based ambulatory external defibrillator programmes and formal cardiopulmonary resuscitation education in high schools. The extension of these programmes to the level of state mandates has been slower, and even when enacted, public funding has usually not been approved.

Physicians participate in the screening, routine medical supervision, and disqualification of student-athletes. In doing so, they should understand that eligibility/disqualification decisions inevitably have associated liability issues. It is the responsibility of physicians to take the lead role in the student-athlete medical assessment process to allow for optimum safety in sports programmes. The first duty of the physician is to protect the health and well-being of the student-athlete. However, because there is potential liability associated with the screening/disqualification process, physicians are wise to develop sound and reasonable strategies that are in strict compliance with the standard of care. This article focusses on cardiac screening and disqualification for participation in sports.

Improved public awareness and advances in medical diagnostics have resulted in the development of criteria to determine eligibility or disqualification for the athlete with cardiovascular abnormalities. Simultaneously, protocols have been developed for athletes with concussion or orthopaedic injuries to guide team physicians and consultants in return-to-play decisions. However, there are currently inadequate data to allow the development of such protocols for athletes with cardiovascular abnormalities who have undergone treatment. Further complicating the decision process is the designation of the team physician as the ultimate authority in making return-to-play decisions – where the team physician often is an employee of the team and supports the team’s goal and players as well as the individual athlete. This review will discuss the ethical dilemma of the team physician and the role of the cardiovascular consultant. Following this, current data and practices regarding return to play will be discussed for the following conditions or diagnoses: following catheter ablation for supraventricular tachycardia; following pacemaker or implantable cardioverter-defibrillator implantation; unexplained syncope; and the athlete with a genetic mutation in the absence of any phenotype of associated disease. These recommendations will undoubtedly continue to evolve and improve and should be considered at this time as a point of departure.

Paediatric pacemaker management is challenging because of the small patient size, complex cardiac anatomy, and unique programming considerations. Hardware placement options include epicardial and transvenous systems. When pacemaker malfunction is suspected, a systematic approach is required to determine whether there is malfunction in pacing, sensing, or no output due to hardware problem. In most cases, simple reprogramming may circumvent the problem and allow retention of the pacemaker system.