It should be emphasized that although these events are devastating, they seem to be uncommon relative to the vast numbers of young athletes participating safely in a wide range of sporting activities [3, 16]. Therefore, information about deaths on the athletic field should not raise undue anxiety and inhibit sports participation. On the other hand, the sudden death of young athletes remains an important medical and societal issue, and uncertainty about the level of risk incurred by apparently healthy young persons participating in sports is a persistent source of concern and anxiety for athletes and their parents, families, coaches, and health care providers. Indeed, the medical profession has a responsibility to create a better-informed public; to pursue, when practical, early detection of diseases or conditions that may cause catastrophic events in young athletes; and to design potentially effective preventive measures.

Although the news media have somewhat sensationalized these tragedies by routinely making the deaths of young athletes widely publicized news events, this very process has also been instrumental in permitting the assembly of data that have defined the causes of these deaths [2, 3]. In this Update (which excludes considerations related to middle-aged athletes and the many benefits of exercise for the general population), I attempt to place into perspective the cardiovascular-related risks associated with organized sports competition and initiatives that may create a safer sports environment for young athletes.

Risks Associated with Unsuspected Cardiovascular Disease

Prevalence and Significance

Although sudden and unexpected cardiovascular deaths occurring in young athletes during organized competitive sports are generally acknowledged to be uncommon, the precise frequency of these deaths is unknown. Many practical obstacles impede the assembly of such data. Although reasonable estimates of the numbers of high school and college athletes are available, systematic tracking of sudden deaths is challenging without a national registry. Consequently, estimates of the prevalence of sudden death that rely on reporting from individual schools and institutions and on news media accounts [2, 3] probably underestimate the occurrence of these events in the United States. The best available estimates, based on national or state populations, suggest that despite the broad participation in organized sports, sudden death from cardiovascular disease in high school or college athletes is rare, occurring in about 1/200 000 [16] to 1/300 000 [3] individual student-athletes per academic year and in about 1/70 000 individual student-athletes over a 3-year high school career [16]. In comparison, higher rates of sudden death related to exercise have been reported for apparently healthy male athletes [17], joggers [18], and marathon racers [19] (about 1/15 000 to 1/50 000 per year).

The infrequent occurrence of deaths on the athletic field suggests that the intense and persistent public interest in these rare but particularly devastating events may be disproportionate to their overall significance in the general population. Indeed, these deaths occur much less commonly in the first three decades of life than other public health problems, such as accidents, homicides, and the consequences of illicit drug use. Nevertheless, the emotional, medical, and societal impact of sudden cardiovascular death in young persons remains high. To much of the public and the medical community, the young competitive athlete is the healthiest member of society. The unexpected collapse of such persons during organized sports activities, which are widely considered safe, inevitably strikes to the core of our personal sensibilities [1].

Causes of Sudden Death

Several reports have documented the causes of nontraumatic sudden death in young persons participating in athletic activities (including organized competitive sports) [1-12]. Such studies incriminate a diverse pathologic substrate of about 20 predominantly congenital cardiovascular conditions; these structural abnormalities are unrelated to the physiologic cardiac adaptations normally associated with systematic athletic training (athlete's heart) [20-23]. Indeed, any disease that can cause sudden death in a young person may also be responsible for such an event in a trained athlete. These cardiovascular lesions usually provide few or no premonitory signs and symptoms and are unlikely to be diagnosed during life [2-9].

The frequency with which particular diseases cause death in competitive athletes varies considerably. Most lesions are responsible for 5% or less of the total; these lesions include ruptured aortic aneurysm (usually in the context of the Marfan syndrome), idiopathic dilated cardiomyopathy, aortic valve stenosis, the long QT syndrome, and myocarditis [2]. The occurrence of myocarditis in this population may be underestimated because of the unique difficulties implicit in validating the clinical and autopsy diagnosis [24-27]. Although myocarditis is usually viral in origin, long-term drug abuse (such as with cocaine) may produce profound and deleterious cardiovascular consequences or death through various mechanisms and morphologic changes that can mimic viral myocarditis, including myocardial ischemia, inflammation, and fibrosis [28-30]. Atherosclerotic coronary artery disease has been cited in numerous reports as an uncommon cause of sudden death in young athletes [2, 3, 5, 6], but some authors have reported higher frequencies of obstructive atherosclerosis, often in the context of single-vessel disease without acute thrombosis [4, 31].

In most published surveys, the single most common cardiovascular lesion causing sudden death in young athletes (about one third of cases) is hypertrophic cardiomyopathy [2, 3, 5, 6, 8]. Hypertrophic cardiomyopathy is a primary and familial cardiac disease with heterogeneous expression for which more than 100 disease-causing mutations in five genes encoding proteins of the sarcomere have been reported [32-39]. The condition is now viewed as more common than previously believed and is identifiable by echocardiography in about 0.2% (1 in 500) of the general population [40]. The association of hypertrophic cardiomyopathy with the risk for sudden and unexpected cardiac death (often during exertion) has been emphasized repeatedly [32-3537, 41-44]. However, the ability to accurately stratify risk for sudden death in any individual athlete with hypertrophic cardiomyopathy is limited by the clinical and pathophysiologic heterogeneity of this disorder and the many mechanisms believed to be responsible for cardiovascular collapse [35, 37, 42].

On the basis of analysis of tertiary referral populations, sudden death in hypertrophic cardiomyopathy seems to have a predilection for young, asymptomatic persons and frequently occurs during moderate or severe exertion [41]. Of note, this clinical profile is consistent with that of young athletes who die suddenly of hypertrophic cardiomyopathy [2]. Indeed, with a disease such as hypertrophic cardiomyopathy, which has the propensity for potentially fatal arrhythmias [43-45], the stress of intense athletic training and competition (as well as associated alterations in blood volume, hydration, and electrolytes) undoubtedly compounds the risk for a sudden cardiac event associated with exertion.

Young athletes who have died suddenly sometimes have nondilated hearts with only modest increases in left ventricular mass (and wall thickness) at autopsy for which the morphologic findings cannot support a definitive diagnosis of hypertrophic cardiomyopathy [2]. An unresolved issue is whether such athletes have a mild morphologic expression of hypertrophic cardiomyopathy [2, 22, 32, 35]; it can also be speculated that athlete's heart [20-23] with substantial degrees of physiologic hypertrophy may have catastrophic consequences under unique circumstances.

The second most common category of diseases responsible for sudden death in young athletes is a spectrum of congenital malformations of the coronary arteries; the most important of these is anomalous origin of the left main coronary artery from the right (anterior) sinus of Valsalva [2-68, 47, 48]. These coronary anomalies are particularly uncommon and are usually identified only at autopsy. Indeed, clinical recognition requires a high index of suspicion. Although definitive clinical diagnosis necessitates coronary arteriography, transthoracic and transesophageal echocardiography [49-51] may strongly suggest (or even identify) such lesions in selected patients.

According to most reports [2-6], arrhythmogenic right ventricular dysplasia is an uncommon cause of sudden death; of note, however, this disease has emerged as the predominant lesion in young trained athletes dying suddenly within the Veneto region of northeastern Italy [7, 9, 52]. The relatively frequent occurrence of arrhythmogenic right ventricular dysplasia as a cause of premature death in this geographic area may reflect a unique genetic substrate. Alternatively, the long-standing Italian national program for the systematic cardiovascular assessment of competitive athletes may have disqualified disproportionate numbers of trained athletes with hypertrophic cardiomyopathy [53]. As a consequence, arrhythmogenic right ventricular dysplasia (which is particularly difficult to detect clinically) may have achieved greater exposure in the athletic population, including the high-risk subset that eventually died. Furthermore, hypertrophic cardiomyopathy may convey a relatively low risk for sudden death in Italy (as recent studies from the northwestern and central regions of that country suggest) [45, 54, 55], thereby accounting for its rarity as a cause of athletic field deaths.

Demographic Characteristics

Most (about 90%) sudden cardiac deaths caused by hypertrophic cardiomyopathy and other lesions reported in athletes have occurred in association with exercise, predominantly in the late afternoon and early evening; this corresponds to the peak periods of competition and practice in organized team sports, such as football and basketball [2]. Of note, this demographic pattern of sudden death in athletes contrasts strikingly with previous observations in patients with hypertrophic cardiomyopathy (who were not involved in athletic activities) for whom a prominent early to mid-morning peak for sudden death was evident, similar to that reported in patients with acute myocardial infarction or angina [56]. Taken together, these observations suggest that in the presence of certain structural cardiovascular diseases, intense physical exertion represents a trigger and important precipitating factor for sudden collapse on the athletic field [2]. These findings also support consensus recommendations that it is both prudent and justifiable to remove athletes with particular cardiac diseases from intense sporting activities to diminish their perceived risk for catastrophic events [57].

Deaths on the athletic field show a striking difference between the sexes: Only about 10% of these deaths occur in female athletes [2, 3]. This difference may exist because women 1) participate less commonly in high school and college sports programs than men (by a 2:1 ratio) [3], 2) are often exposed to generally less intensive training demands than men, 3) do not participate in sports [such as football] that are associated with the greatest risk for sudden death, and 4) less commonly have certain cardiovascular lesions responsible for sudden death (in particular, hypertrophic cardiomyopathy) [32-35].

Race also seems to play a role in deaths on the athletic field; evidence suggests that hypertrophic cardiomyopathy is an important cause of sudden death in young African-American male athletes [2, 4, 58]. This observation is of interest because it contrasts sharply with the infrequent reporting of black patients with hypertrophic cardiomyopathy in hospital-based tertiary center populations [58]. Therefore, hypertrophic cardiomyopathy is usually encountered in young African Americans when it results in sudden and unexpected death during competitive sports. These data emphasize the disproportionate access to subspecialty medical care and sophisticated cardiovascular diagnosis in the African-American and white communities in the United States. Therefore, it is less likely that young black males will be identified with hypertrophic cardiomyopathy and consequently disqualified from competition to reduce their risk for sudden death (in accordance with the recommendations of the 26th Bethesda Conference, discussed later in this paper) [57].

Mechanisms and Resuscitation

The precise mechanism ultimately responsible for sudden death in young athletes depends on the disease state involved. In most cases, however, including athletes with hypertrophic cardiomyopathy, death probably results from electrical instability and ventricular tachyarrhythmias. Rarely is an athlete with cardiovascular disease successfully resuscitated after cardiac arrest on the athletic field.

It has been suggested that widespread availability of automatic external defibrillators designed for public access would result in the survival of many athletes experiencing cardiac arrest [59]. Although some benefits undoubtedly ensue from this strategy, the great infrequency with which these events occur would itself represent an important obstacle to efficient resuscitation practice [2, 3].

Differential Diagnosis of Cardiac Disease and Athlete's Heart

In some trained athletes with left ventricular hypertrophy, it may be difficult to distinguish physiologic cardiac adaptations to athletic training (that is, athlete's heart) from pathologic conditions [60]. This differential diagnosis may involve athletes with borderline increased thickness of the left ventricular wall (the "gray zone"; thickness of 13 to 15 mm), creating confusion between the extreme morphologic consequences of training and hypertrophic cardiomyopathy; such distinctions are often resolvable with clinical assessment and echocardiography [60]. The substantial genetic heterogeneity in hypertrophic cardiomyopathy and the expensive, time-intensive techniques of genotyping do not yet permit laboratory-based DNA diagnosis to be routinely available in this clinical setting [61]. In other athletes, a left ventricular cavity that is particularly enlarged ( 60 mm) may suggest dilated cardiomyopathy (Pelliccia A, Culasso F, Di Paolo F, Caselli G, Maron BJ. Physiologic left ventricular cavity dilatation in elite athletes. Submitted for publication).

The clinical distinction between athlete's heart and cardiac disease has important implications for trained athletes because identification of cardiovascular disease may be the basis for disqualification from competition in an effort to minimize risk [57, 62]. By the same token, the improper diagnosis of cardiac disease in an athlete may lead to unnecessary withdrawal from athletics, depriving that person of the benefits of sports.

Preparticipation Screening and Detection of Cardiovascular Abnormalities

Detection of preexisting cardiovascular abnormalities with the potential for substantial morbidity or sudden death is an important objective of preparticipation screening currently in place in U.S. high schools and colleges [63]. Large-scale athletic screening has traditionally been performed in the context of a history (personal and family) and physical examination. However, the practicality and utility of the screening process are limited by the uncommon occurrence of these relevant cardiovascular lesions in the general population and the large size of the competitive athletic population (perhaps 8 to 10 million persons every year). Indeed, one retrospective study showed that cardiovascular abnormalities were suspected by history and physical examination screening in only 3% of the high school and college athletes who ultimately died suddenly of cardiac disease [2]. Of note, prospective studies in large athletic populations using echocardiography and electrocardiography have also shown a low yield of identifiable cardiovascular disease [64-66].

Nevertheless, an American Heart Association consensus panel [63] recently supported the principle of preparticipation cardiovascular screening for young competitive athletes on both medical and ethical grounds. The panel recommended a history (personal and family) and physical examination targeted to the cardiovascular lesions known to be responsible for sudden death or disease progression; although this method is imperfect, the panel nonetheless considered it the most practical and best available strategy for screening large populations of young athletes. In addition, the panel offered specific recommendations on the composition of the history and physical examination (Table 1) and the selection of examiners.

In its current form, the preparticipation screening process for high school athletes seems to be substantially flawed. A major impediment lies in the design of the approved history and physical examination forms that represent guidelines to the examiners in 43 U.S. states (including the District of Columbia) (the other 8 states have no such questionnaires) [67]. Indeed, 40% of the states either have no formal screening requirement or approved history and physical examination questionnaires or have forms that were judged inadequate when measured against the American Heart Association 1996 consensus panel screening guidelines [63]. Therefore, there is a crucial need to consider ways for standardizing the preparticipation history and physical examination on a national basis (as well as requirements for the expertise and training of the designated examiners) so that they conform more closely to the specific American Heart Association recommendations [63]. Indeed, preparticipation sports examinations are performed by a wide variety of health care workers with vastly different levels of training and expertise in the diagnosis of cardiovascular disease. All states that have a specific policy sanction physicians to perform preparticipation examinations. In addition, 21 states also permit nurses or physician assistants to administer examinations, and 11 states specifically provide for practitioners with limited cardiovascular training (such as chiropractors and naturopathic clinicians). An improved screening process will undoubtedly result in the detection of more athletes with important lesions and ultimately, by virtue of treatment or disqualification from intense sports, will diminish the overall risk for sudden death.

The addition of noninvasive testing (such as echocardiography or electrocardiography) to preparticipation screening would enhance the identification of many abnormalities, particularly hypertrophic cardiomyopathy [63]. The American Heart Association panel [63], although not specifically discouraging individual initiatives for large-scale screening that incorporates testing, concluded that consistent implementation of such strategies on a national scale in the United States was impractical and prohibitive because of the considerable size of the athlete population, cost-efficacy considerations, and such issues as anxiety (and the possibility of unjustified disqualification) created by false-positive and borderline test results. The largest screening effort for the detection of cardiovascular abnormalities in athletic populations, routinely involving electrocardiography, has been ongoing in Italy since 1982 as part of a national evaluation program for competitive athletes [53, 68]. It is unlikely that such a program will ever be implemented in the United States, given the much larger population (five times that of Italy) and other practical considerations, including obstacles to funding.

It should be emphasized, however, that no large-scale screening effort (even with noninvasive testing) can detect all important lesions in affected athletes [63]. Consequently, medical clearance for sports should not promulgate a false sense of security or an unrealistic expectation that the athlete is free of potentially fatal cardiovascular disease. Indeed, physicians and other health care providers who perform preparticipation evaluations probably bear a responsibility to inform athletes and their families of the limitations inherent in screening for cardiovascular disease, as well as the small risks that may remain for athletes even after normal findings on a screening examination.

Preparticipation examinations in the United States occur largely at the discretion of the examining physician as customary practice, based on requirements of high schools and colleges. A considerably different circumstance has existed in Italy since 1971 in the form of benevolent government legislation (the Medical Protection of Athletic Activities Act) that mandates preventive medical evaluations for all competitive athletes [53]. In this unique program, supported financially by the government, all citizens 12 to 35 years of age who wish to engage in organized sports activities must achieve annual medical clearance from an approved physician stipulating that they have no abnormalities that could unacceptably increase the risk for sudden death during training or competition. Since 1982, more detailed guidelines for these preparticipation examinations have been formulated to include history and physical examination, 12-lead electrocardiography, and exercise and pulmonary function tests. Since 1994, echocardiography has been specifically required only in selected professional sports (soccer, boxing, and cycling). Under Italian law, the examining physician is primarily responsible for the accuracy of this clinical assessment and stands as the final judge of eligibility for sports by issuing an official certification of medical clearance. In the event of an incorrect medical diagnosis that leads directly to the impaired health or the death of an athlete, the physician who sanctioned athletic competition can be held accountable in criminal and civil court.

Eligibility Considerations for Athletes Known To Have Cardiovascular Disease

When a significant cardiovascular abnormality is identified in a competitive athlete, certain considerations arise with respect to the magnitude of risk for sudden cardiac death with continued participation in organized sports and the appropriate criteria with which to determine whether a given athlete will probably benefit from disqualification. In this regard, the 26th Bethesda Conference, sponsored by the American College of Cardiology, offers specific and prospective consensus panel recommendations [57] for athletic eligibility. This reference document considers the nature and severity of approximately 70 relevant cardiovascular abnormalities and diseases, the character of the sports training and competition, and available information on risk stratification for cardiac events. The recommendations of the 26th Bethesda Conference [57] are predicated on the likelihood that intense athletic training and competition increase the risk for sudden cardiac death or disease progression in athletes with certain structural heart diseases [2]. Although it is not yet possible to precisely predict or quantify that risk, it is a prudent presumption that the temporary or permanent withdrawal of selected athletes from intense competitive sports mitigates the perceived risk. These considerations are particularly relevant to a heterogeneous disease such as hypertrophic cardiomyopathy, in which risk stratification remains imprecise [35, 37, 42].

The fact that it is difficult to stratify risk among individual athletes with hypertrophic cardiomyopathy is reflected in the recommendations of the 26th Bethesda Conference [57] for athletic eligibility. These guidelines are conservative and homogeneous for young athletes with an unequivocal diagnosis of hypertrophic cardiomyopathy. The recommendations advise that such athletes withdraw from intense competitive sports.

Both the 26th Bethesda Conference report (1994) [57] and the American Heart Association screening recommendations (1996) [63] provide clear benchmarks for the expected standards of care that may be used to resolve medicolegal disputes in individual cases. Indeed, the 26th Bethesda Conference was recently cited by a U.S. Court of Appeals as consensus medical guidelines that the team physician should rely on in appropriately formulating decisions on the disqualification of competitive athletes with cardiovascular disease [69].

Cardiac Risks on the Athletic Field Unrelated to Underlying Cardiovascular Disease

Although sudden death in young athletes due largely to congenital heart diseases [2-12] has achieved great visibility, other unusual risks of organized or recreational sports activity leading to cardiovascular collapse have recently been emphasized. For example, although uncommon, virtually instantaneous cardiac arrest may result from a relatively modest and nonpenetrating blow to the chest-in the absence of underlying cardiovascular disease [13, 14, 70] or structural injury to the chest wall or heart itself.

In such occurrences, which have been called commotio cordis ("disturbed or agitated heart motion") [71], blunt chest impact over the anatomic position of the heart is usually produced by a projectile (most commonly a baseball) or by bodily collision with another athlete. The chest blow is not perceived as unusual for the sporting event or necessarily of sufficient magnitude to result in a catastrophe. The most common scenario during competitive sports is that of a young baseball player struck in the chest, while batting, by a pitched ball thrown from a standard distance. Of note, many of these catastrophes have occurred in purely recreational situations at home or on the playground, with the fatal injuries often produced by family members. Although the precise mechanisms responsible for the cardiac arrest are not known with certainty, a recently developed experimental model in swine closely simulates the clinical profile of commotio cordis and provides important insights [72]. The model shows that a precordial blow can create devastating electrophysiologic consequences, largely by virtue of its precise timing. When chest impact occurred with modest force (30 miles per hour) during a narrow window of 15 to 30 ms before the T-wave peak, thereby interfering with the vulnerable phase of repolarization, ventricular fibrillation occurred instantaneously and reproducibly [72].

Furthermore, softer-than-standard safety baseballs reduced the risk for ventricular fibrillation, suggesting that sudden death from commotio cordis during certain youth sporting activities may be prevented by modifying athletic equipment [72]. However, the low event rate for commotio cordis creates an obstacle to documenting the effectiveness of any protective intervention. In addition, about 15% of reported victims of commotio cordis were equipped with protective padding over some portion of the anterior chest wall at the time of their injury and collapse [70]. Indeed, it is probably impossible to achieve absolute protection and "zero risk" from all adverse eventualities of sports participation while at the same time preserving the integrity of competition.

Commotio cordis events are not uniformly fatal, and about 10% of reported victims are known to have survived, usually because of reasonably prompt cardiopulmonary resuscitation and defibrillation [14, 70]. With enhanced public awareness of this syndrome, emergency measures are more likely to be promptly implemented on the athletic field, possibly avoiding many future catastrophes. Nonpenetrating chest blows (particularly when delivered by a soccer ball at high velocity) can also produce nonfatal, acute myocardial infarction in otherwise normal athletes [73]. Although the mechanism by which these events occur is uncertain, myocardial ischemia and infarction may result from direct compression of a coronary artery that produces spasm or possibly coronary thrombosis.