The sudden cardiac death of athletes is typically defined as natural, unexpected death from cardiac arrest within one hour of the onset of collapse symptoms, excluding additional time on mechanical life support. (Wider definitions of sudden death are also in use, but not usually applied to the athletic situation.) Most causes relate to congenital or acquired cardiovascular disease with no symptoms noted before the fatal event. The prevalence of any single, associated condition is low, with the most common affecting nearly 0.5% of the general population, and the sensitivity and specificity of common screening tests leave much to be desired. The single most important predictor is fainting or near-fainting during exercise, which should require detailed explanation and investigation. The victims include many well-known names, especially in professional association football, and close relatives are often at risk for similar cardiac problems.
Causes The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review:
While most causes of sudden cardiac death relate to congenital or acquired cardiovascular disease, an exception is commotio cordis, in which the heart is structurally normal but a potentially fatal loss of rhythm occurs because of the accident of timing of a blow to the chest. Its fatality rate is about 65% even with prompt CPR and defibrillation, and more than 80% without.
Before age 35 Age 35 serves as an approximate borderline for the likely cause of sudden cardiac death. Before age 35, congenital abnormalities of the heart and blood vessels predominate. These are usually asymptomatic prior to the fatal event, although not invariably so. Congenital cardiovascular deaths are reported to occur disproportionately in African-American athletes.
After age 35 After age 35, acquired coronary artery disease predominates (80%), and this is true regardless of the athlete's former level of fitness. Various performance-enhancing drugs can increase cardiac risk, though evidence has been inconclusive about their involvement in sudden cardiac deaths.
Genetics
Cardiomyopathies Cardiomyopathies are generally inherited as autosomal dominants, although recessive forms have been described, and dilated cardiomyopathy can also be inherited in an X-linked pattern. Consequently, in addition to tragedy involving an athlete who succumbs, there are medical implications for close relatives. Among family members of index cases, more than 300 causative mutations have been identified. However, not all mutations have the same potential for severe outcomes, and there is not yet a clear understanding of how these mutations (which affect the same myosin protein molecule) can lead to the dramatically different clinical characteristics and outcomes associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Since HCM, as an example, is typically an autosomal dominant trait, each child of an HCM parent has a 50% chance of inheriting the mutation. In individuals without a family history, also known as sporadic cases, a common cause of the disease may be a "de novo" mutation of the gene that produces the β-myosin heavy chain, with two out of seven tested patients falling into this category.
Channelopathies
Sudden cardiac death can usually be attributed to cardiovascular disease or commotio cordis, but about 20% of cases show no obvious cause and remain undiagnosed after autopsy. Interest in these "autopsy-negative" deaths has centered around the "ion channelopathies". These electrolyte channels are pores regulating the movement of sodium, potassium and calcium ions into cardiac cells, collectively responsible for creating and controlling the electrical signals that govern the heart's rhythm. Abnormalities in this system occur in relatively rare genetic diseases such as Long QT syndrome, Brugada syndrome, and Catecholaminergic polymorphic ventricular tachycardia, all associated with sudden death. Consequently, autopsy-negative sudden cardiac deaths (no physical abnormalities identified) may comprise a larger part of the channelopathies than previously anticipated.
Heritable connective tissue diseases
Heritable connective tissue diseases are rare, each disorder estimated at one to ten per 100,000, of which Marfan syndrome is the most common. It is carried by the FBN1 gene on chromosome 15, which encodes the connective protein fibrillin-1, inherited as a dominant trait. This protein is essential for synthesis and maintenance of elastic fibers. Since these fibers are particularly abundant in the aorta, ligaments, and the ciliary zonules of the eye, these areas are among the worst affected. Everyone has a pair of FBN1 genes and, because transmission is dominant, those who have inherited one affected FBN1 gene from either parent will have Marfan syndrome. Although it is most frequently inherited as an autosomal dominant, there is no family history in 25% of cases. Recruiting practices aimed at attracting athletes who are unusually tall or who have an unusually wide arm span (characteristics of Marfan syndrome) can increase the prevalence of the syndrome within sports such as basketball and volleyball.
DNA testing After a disease-causing mutation has been identified in an index case (which is not always accomplished conclusively), the main task is genetic identification of carriers within a pedigree, a sequential process known as "cascade testing". Family members with the same mutation may show different severities of disease, a phenomenon known as "variable penetrance". As a result, some may remain asymptomatic, with little lifelong evidence of disease. Nevertheless, their children remain at risk of inheriting the disorder and potentially being more severely affected.
Screening
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