Sudden Cardiac Death in Sports

Problem and objective: To inform about the incidence, causes and prevention measures of sudden cardiac death in sports.

Methods: A literature search was performed (PubMed, Web of Science, Researchgate) using the terms sudden cardiac death (SCD), sudden cardiac arrest (SCA), sudden death, cardiopulmonary resuscitation, sport, exercise and athlete. Observational studies, systematic reviews and meta-analyses that examined SCD/SCA during exercise or up to one hour afterwards in recreational, competitive or elite athletes were considered.

Results: Of 6350 study titles and abstracts 11 full-text studies were included in this clinical review. When the incidence was calculated based on multiple sports, it varied between populations and ranged from 0.1 to 2.9/100,000 athlete-years (AY). The incidence was highest in male professional basketball players, with 19/100,000 AY. The most frequent cause of SCD/SCA in athletes >35 years was coronary artery disease (CAD), while in younger athletes the predominating underlying pathologies (autopsy-negative sudden unexplained death, myocarditis, cardiomyopathies, coronary artery anomalies and premature CAD) differed by region. The most effective screening tool for cardiovascular disease in athletes is the ECG. Survival after CPR is substantially influenced by the use of an automated external defibrillator (AED).

Discussion: SCD/SCA in athletes is a rare but very tragic event. Incidence rates in athletes differ among populations, studies, and sports. Some degree of underreporting can be assumed as there is no mandatory reporting of sports-related SCD/SCA in most countries and few scientific registries exist. Potentially, primary screening measures could be adapted to the regionally different causes of SCD/SCA. In addition, training athletes and staff in the use of an AED is paramount to improving survival rates.

Key Words: Athletes, Cardiac Arrest, Cardiovascular Disease

Regular physical activity has many positive effects on health, such as general mental well-being or the morphological and functional adaptation processes of the heart. However, in athletes with underlying cardiovascular diseases physical activity can also trigger fatal arrhythmias. A sports-related sudden cardiac death (SCD) is defined as an unexpected death occurring during exercise or within 1 hour after cessation of activity. Survival due to successful defibrillation and/or cardiopulmonary resuscitation (CPR) is defined as sudden cardiac arrest (SCA). SCD/SCA might occur in athletes with a structurally abnormal or normal heart. In the latter case, an extracardiac cause is usually excluded by autopsy or extensive medical examinations, and there is a coexisting history consistent with cardiac death. SCD/SCA is a rare event but regularly entails great public attention when it occurs in young apparently healthy athletes.

To calculate the incidence of SCD/SCA in athletes, it is of great relevance to determine a precise numerator (cases identified) and a defined denominator (population per time). Factors that may influence numerators and denominators include the following: the definition of an athlete, type of sport, age of the population studied, data acquisition (e.g., media reports, online platforms for reporting cases, registries ideally based on autopsy and outpatient data), whether data reporting is mandatory or not, the inclusion or exclusion of specific cardiac events based on time and location (8, 13).

To the best of our knowledge, there is no review so far that simultaneously highlights the national differences in SCD/SCA with respect to incidence rates, the leading causes of death, sports most frequently involved, and resuscitation efforts performed.

Therefore, the aim of this clinical review was to compare internationally the results of SCD/SCA registry studies in athletes of different sports and performance levels.

A literature search in PubMed, Web of Science, and Researchgate was performed from June to September 2022 using a combination of keywords and operators (Boolean search type) to produce accurate search results: (“sudden cardiac death” OR “sudden death” OR “sudden cardiac arrest” OR “cardiopulmonary reanimation”) AND (“sport” OR “exercise” OR “athlete”). Observational studies, systematic reviews, and meta-analyses on sports-related SCD/SCA, defined as cardiac arrest during exercise or up to one hour afterwards in recreational, competitive or elite athletes were included. Case reports, poster presentations, studies lacking medical details on the causes of SCD/SCA, and studies reporting SCD/SCA unrelated to exercise were excluded. Screening was performed by one researcher, who discussed the results by applying inclusion/exclusion criteria with another person in the same working group. No significant disagreement occurred, but a third consensus reviewer was available. Finally, SCD/SCA studies representing data on a national level were included. In the case that multiple studies from one country were available, only the study with the most extensive data set was included. A flowchart of the literature search is presented separately (see supplementary material online). Incidence rates are presented as event rate/100,000 athlete years (AY).

Out of 6350 study titles and abstracts screened 23 full-text articles were assessed for eligibility. Of these, 11 studies reporting SCD/SCA on a national basis were included. The vast majority of the studies (10 of 11, 91%) included autopsy reports (table 1). The incidence varied widely among the populations studied, ranging from 0.1 to 2.9/100,000 AY in multiple sports. However, in individual sports, the incidence was significantly higher (18), with up to 19/100,000 AY (12).

Epidemiology
Incidence rates varied widely by study design, type and level of sport, population characteristics and data acquisition. In a recent meta-analysis including 40 studies of SCD/SCA in young athletes of various sports, the overall incidence was found to be at 0.98/100,000 AY (16). In contrast, the incidence in US-college athletes, a more homogeneous study population, was higher at 1.9/100,000 AY, with a peak of 1:9000 AY (11/100,000 AY), in male basketball players (12). In division 1 male basketball players, SCD/SCA incidence was even 1:5200 AY (19/100,000 AY), which is more than 10 times the risk of the normal athlete population (12). Furthermore, a cardiac screening of young adolescent football players in the UK revealed an incidence of 6.8/100,000 AY (18). It appears that higher incidence rates are observed in sport-specific studies, possibly related to easier accessibility and improved information flow within a single sports community. In comparison, for studies involving multiple sports and inhomogeneous populations, the calculated incidences could probably be less accurate (16).

The individual risk of SCD/SCA depends on several demographic characteristics such as age, gender, ethnicity and athlete status (3, 5, 8, 12, 20). It is uncontroversial that the risk for SCD/SCA increases with age. Furthermore, male and high-level competitive athletes show higher incidence rate ratios (IRR) than females and athletes competing at a lower level (table 2). In this context, it should be mentioned that table 2 shows a wide range of male to female IRR (2.4-23.0). Nevertheless, some studies also found a lower risk for competitive athletes compared to non-athletes (IRR 0.2) (1). There is also evidence black athletes show higher IRR than white athletes (IRR 3.2) and certain entities such as cardiomyopathies (20% vs. 10%) and coronary artery anomalies (10% vs. 5%) are more frequent among nonwhite than white athletes, respectively (13, 20).

Aetiology
The most common cause of SCD/SCA in athletes >35 years was coronary artery disease (CAD). In younger athletes ≤35 years the predominating underlying pathologies seem to vary by region (8). The recent publication of the FIFA Sudden Death Registry included 617 cases from 67 countries (all continents). In young football players, the leading causes were cardiomyopathy in South America, coronary artery anomaly in North America and autopsy-negative sudden unexplained death (SUD) in Europe (8). Regional differences in the causes of SCD/SCA also seem to apply to other sports when comparing the results of national registries separately. The predominating causes of SCD/SCA in young athletes were SUD in the USA, cardiomyopathies in Spain, Italy and France, and premature CAD in Germany, Norway and Switzerland (1, 3, 5, 12, 18, 19, 21, 25).

In addition, young athletes ≤35 years may have electrical heart diseases, particularly inherited cardiac channelopathies such as long-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT), although these rare conditions account for no more than 4% of the total spectrum of cardiovascular causes (3,8, 12, 19, 20). Another entity in young athletes associated with SCD/SCA is Wolff-Parkinson-White (WPW) syndrome (up to 10% of cardiac conditions of adolescent football players in the UK), in which accessory electrical conduction leads to pre-excitation of the heart, potentially triggering ventricular fibrillation (12, 18, 19). In contrast to cardiac channelopathies, return to sport is possible in athletes with WPW syndrome after an ablation (in most cases) is performed (18).

SCD/SCA in Different Sports
Sports with high cardiocirculatory stress are more frequently associated with SCD/SCA (5, 12, 20). In this context, regional differences in the frequency of individual and team sports can be observed. Cycling is the sport most frequently associated with SCA/SCD in France (19), Sweden (26), Spain (21) and Luxembourg (2), while it is basketball in the USA (12), baseball in Japan (15) and football in Italy (5) and Germany (3). Running is among the top 3 sports associated with SCD/SCA in Australia (11), Germany (3), Spain (21) France (19) and Luxembourg (2).

Circumstances of CPR
The FIFA Sudden Death Registry examined the circumstances of out-of hospital CPR in football players worldwide (8). Prompt CPR resulted in a survival rate of 35% and 50% when performed by lay persons and CPR-trained staff, respectively. Survival rate even increased to 85% when CPR was initiated by trained staff and an automated external defibrillator (AED) was used. Importantly, players themselves performed CPR most frequently before emergency medical services arrived. Survival rates in young US competitive athletes were 83% when a certified athletic trainer was on site and involved in resuscitation and 89% when an AED was used on site (6). A prospective and comprehensive national survey in France, using ambulance service reporting and media search, found most cases of sports-related SCD/SCA (93%) in the general population were witnessed, whereas bystander CPR was performed in only 31% of cases (19). In Sweden sports-related compared to non-sports related out-of-hospital cardiac arrests were more often witnessed (89% vs. 79%), had higher rates of bystander CPR (80% vs. 61%) and were more frequently connected to an AED (20% vs. 5%) (26).

In this clinical review, the incidence of SCD/SCA in athletes ranged from 0.1 to 2.9/100,000 AY with respect to multiple sports, which is consistent with a previous traditional estimate of 1-3/100,000 AY (8, 12, 26). Higher incidence rates were only observed in single-sport studies, possibly related to easier accessibility and improved information flow within a single sports community. Thus, for adolescent football players or male professional basketball players, the incidence showed peaks of 6.8/100,000 AY and 19/100,000 AY, respectively. Another reason for the heterogeneity in incidence rates may be that some of the underlying diseases are more prevalent in certain athlete populations and, as seen from a previous study (8), that they also vary by region.

Causes of SCD/SCA and Primary Prevention Measures
CAD was by far the most frequent cause of SCD/SCA in athletes >35 years. In younger athletes ≤35 years various pathologies were observed that varied by region. The predominating causes of SCD/SCA in young athletes were SUD in USA, cardiomyopathies in Spain, Italy, and France and premature CAD in Germany, Norway, Luxembourg and Switzerland (1, 2, 3, 5, 12, 19, 21, 25). Consistent with a previous study, there seem to be regional distribution patterns of the underlying pathologies in young athletes (8). Therefore, it is conceivable that primary screening measures might be adapted to the regionally different causes of SCD/SCA. However, it should be kept in mind that not all entities can be clearly diagnosed. Cardiac ion channelopathies, which have recently been suggested to be responsible for 30% of autopsy-negative results (4), are very difficult to detect. Nevertheless, the diagnostic value of ECGs for screening of electrical heart disease should be emphasized, especially when athlete-specific ECG criteria are applied (7). In this context, one essential point should be noted: the most effective screening tool for cardiovascular disease in athletes is ECG. This is reflected not only in a five times higher sensitivity than history but also in ten times higher sensitivity than physical examination (14).
The diagnosis of coronary artery anomalies (leading cause of young football players in North America) is limited in the setting of non-invasive imaging (17, 18), which is, moreover, no standard as part of the pre-competition medical assessment (PCMA) in young athletes (23). Nevertheless, any echocardiography with a medical indication in the PCMA of a young athlete should include the search for aberrant origins of the coronary arteries. Furthermore, the accuracy of exercise stress tests to detect CAD in populations with low pretest probability, such as asymptomatic athletes participating in high-intensity sports, is limited (9). Further investigations, such as a coronary computed tomography angiography to diagnose a suspected premature CAD should therefore only be considered in case of a clear family history or typical cardiac symptoms during exercise in athletes ≤35 years of age.

Cardiomyopathies can usually be detected by echocardiography. In this context, it should be mentioned that the diagnosis of early-stage cardiomyopathy in young athletes is challenging, and close follow-up is recommended (18). In general, for the PCMA of an athlete, it can be stated that in addition to an extensive family history and clinical examination, potential risk factors for SCD/SCA such as age, gender, ethnicity, and competition level should be considered. Since sports-related SCD/SCA is on average 14 times less common in females, there is debate as to whether PCMA needs to be individualized for female athletes (24). Given that SUD and channelopathies represent a significant proportion of underlying causes of SCD/SCA in female athletes, attention should be paid to prodromal symptoms and family history (24).

Secondary Prevention Measures
A sports-related cardiac arrest is a potentially survivable event, if resuscitation efforts are initiated promptly. After a 5-minute delay in CPR, irreversible damage to the brain occurs in the absence of blood flow (22). This „no-flow time“ (time from cardiac arrest to CPR) significantly determines the overall outcome of the victim and can be kept very low if athletes and staff are well trained in CPR, which means being able to recognize a cardiac arrest and immediately start sufficient chest compressions. A recent study found that the likelihood of a favorable outcome in CPR decreases by 13% for every additional minute of no-flow time until high-quality CPR is performed (10). In the FIFA Sudden Death Registry delayed CPR (inactivity until the arrival of paramedics or first responders) was observed due to misinterpretation of symptoms or unawareness (8). Only one case survived delayed CPR but retained irreversible neurologic damage. Because football players themselves most often performed CPR before emergency medical services arrived, CPR by athletes, not just staff, should be encouraged through regular CPR training (8).

Methodological Considerations and Limitations
This clinical review was not subject to the same requirements as a systematic review, and therefore the literature search performed may be incomplete. Furthermore, it is assumed that previous incidence rates on SCD/SCA are likely underestimated (8, 20, 26). The true incidence of SCD/SCA in athletes is most likely still unknown. The main reason for this could be that there is no mandatory reporting in most countries. Another reason is the way incidence rates are calculated. A recent meta-analysis examined the incidence of SCD/SCA in athletes and military personnel (16). It was found that the calculation of incidence was highly dependent on study design. The risk of bias was lower in studies that considered a number of the following parameters: well-defined numerators, denominators and cases (circumstances of SCD/SCA during sport or at rest, information on whether resuscitation was performed), duration of the study, data sources (media articles provide less reliable data than medical and autopsy reports) and characteristics (age, sex, and level of physical activity) of the population studied. In this context, the gold standard to calculate the true incidence of SCD/SCA on a national level would be outpatient data collection in close cooperation with the emergency medical services. In Sweden, such a registry exists with an estimated detection rate of almost 100%(26).

SCD/SCA in athletes is a rare but important topic. Cardiomyopathies, premature CAD, coronary artery anomalies, and SUD (suggestive of cardiac ion channelopathies) are most prevalent in young athletes ≤35 years. In older athletes CAD is the most common cause of SCD/SCA by far. Since the underlying pathologies for SCD/SCA of younger athletes seem to vary by region, primary prevention measures could be adapted accordingly. The incidence of SCD/SCA in athletes is likely still underestimated, making more outpatient data collection necessary. Therapy and prognosis rely on regular and adequate training in CPR as well as on the availability of AEDs on site.

Conflict of Interest
The authors have no conflict of interest.