John Strelow is a fifteen-year-old male child with no prior history of serious illness. He is a freshman at Brementown High School (ninth grade) and is interested in participating in the school’s highly competitive athletics program. He wishes to join the school’s freshmen football team. As a requirement for participation, he goes for a preparticipation health screening at his local pediatrician. The physician does a cardiac examination looking for heart murmurs and checks John’s blood pressure in a sitting position, all of which are normal. He asks John if he has ever experienced chest pain, shortness of breath, or palpitations. John answers in the negative. Finally, the pediatrician asks John about heart disease or unexplained early death in his family. John replies that his father died in a farm accident having been crushed in a combine at age forty and that he has no other known paternal relatives. John’s mother has been diagnosed with mild hypertension and elevated blood lipids but is otherwise healthy. John has a younger sister (age twelve) who has only minor medical problems. The pediatrician approves John’s participation (warning him about adequate fluid intake and the danger of excessive exercise during periods of high heat and humidity). John begins a preparticipation workout session at the school on a hot, humid September day and tells the coach he feels a bit dizzy and that his vision temporarily “grayed out.” The coach instructs him to rest in the shade for a few minutes. Feeling better, John continues his workout telling the coach he feels fine. On returning home, John mentions the episode to his mother who is concerned. John has not told the coach (or his mother) that he felt short of breath for the entire workout. John participates in several additional training sessions and has several more episodes of shortness of breath coming close to fainting twice. He hides this from the trainer and coach, wanting to participate in the first freshmen team game against Muenster High. During the game, John collapses suddenly. Paramedical aid is on hand, but John cannot be resuscitated. He is pronounced dead on arrival at Saint Ann Regional Hospital. His autopsy, requested by the county medical examiner, shows cardiac abnormalities. There is asymmetric thickening of the left ventricle with excess septal wall hypertrophy. The ventricular chamber is small, and there is a suggestion that vascular outflow from the left ventricle might have been impeded. A tissue sample from the left ventricle is examined and disorganization of the cardiac myocytes is noted. The medical examiner records the case as sudden cardiac death related to presumptive hypertrophic cardiomyopathy resulting in cardiac arrhythmia.
Discussion Sudden cardiac death (SCD) in preadolescent and adolescent children is a tragic event and comes to general attention when those deaths are involved in school athletic programs. Because of understandable publicity, these deaths appear common when, in fact, they are unusual. A U.S. Registry of Sudden Death in Athletes has collected data for over thirty years. There are about 75 cardiovascular deaths per year in young athletes, compared to about 115 deaths among young athletes from all causes. The overall incidence of cardiac death in young athletes is estimated to be between 0.5 and 0.7 deaths per 100,000 person years. Deaths from motor vehicle accidents are 2,500 times more common in the same age group. It should be noted that estimates of SCD in school athletes have been criticized because they are difficult to interpret based on the large number of variables in these studies. Some believe the true figures to be twice as high (1 death per 100,000) or perhaps even higher. However, for U.S. high school students, the incidence of sudden cardiac death among athletes as compared to nonathletes was over 3.5 times higher. Clearly participatory high school athletics does present an elevated risk for SCD, but the overall risk is very small when compared to the more common causes of death among the young (notably trauma by accident, homicide, or suicide). What is responsible for the increased risk of SCD in young athletes? In the above noted registry, hypertrophic cardiomyopathy (HCM), defined as increased asymmetric left ventricular wall thickness in the absence of other causes, was the most common cause of SCD in athletes, being responsible for 35 percent of deaths. Other studies report the incidence of proven and possible HCM in cases of SCD ranging from 11 percent (in NCAA athletes) to 7 percent (in the U.S. military) to 37 percent (in athletes in the United Kingdom). Myocarditis, often cited as a cause of SCD in young athletes, was less common (6 percent of deaths in the U.S. Registry). The variation in frequency of HCM in SCD is likely related to differences in diagnostic criteria and, more important, to the fact that at least 60 percent of HCM cases are genetic in origin with mutations in three genes being responsible for over 80 percent of cases. The disease is most often dominant, and familial clusters of affected individuals may have a strong effect on observed frequencies. The disease is common with a prevalence of 1 in 500 and, although many cases are asymptomatic, 10 percent of patients ultimately develop heart failure. Stress accentuates symptoms in HCM patients, and in some cases the risk for SCD may be as high as 4 to 5 percent per year. Although certain high-risk HCM mutations have been defined, the correlation between mutations and presence and severity of cardiac disease is poor. Hence, there is considerable controversy about the utility of genetic analysis (although it may be useful in some families). Considering the relatively high frequency of HCM in at least some populations and the publicity and trauma attendant with SCD in a young athlete, proposals have been made to increase screening criteria. Currently a fourteen-element preparticipation screen is suggested by the American Heart Association for competitive athletics (TABLE 11-3). Some, but not all, of these elements were utilized in this case. Major problems are standardization between screenings and qualifications for the person doing the screening. Even with effective screening, not all cases of HCM will be detected. Also, youth might be expected to be less than forthcoming in reporting symptoms. Screening using 12-lead ECG, which is effective in detecting ventricular hypertrophy, has been suggested as a mandatory component to screening. However, the test is costly, controversial in terms of specificity and sensitivity, and is technically challenging. Mandatory screening with 12-lead ECG is not recommended for young athletes and nonathletes by the American Heart Association or the American College of Cardiology because there is no evidence of benefit. Serious ethical concerns exist regarding the provision of specialized screening solely to athletes when in aggregate there are far more cases of HCM in the nonathlete population.
TABLE 11-3
When HCM is suspected, highly effective specialized, noninvasive diagnostic procedures are available (two-dimensional echocardiography and cardiac MRI investigations). Today these procedures are far too costly and too technically demanding for use in screening normal populations. Finally, a diagnosis of HCM need not prevent a person from engaging in a program of physical activity of a stress level appropriate to the specifics of their particular case.
Etiology and Pathogenesis
Sudden cardiac death likely from cardiac arrhythmia as a result of hypertrophic cardiomyopathy.
Questions
1. The case notes that there are far more cases in aggregate of HCM in nonathletes than in athletes. Why is this? Given that fact, would you support mandatory screening for high school athletes?
2. There are racial and sex-based differences in SCD frequency in athletes (not discussed in this case). What could be some of the factors responsible for these differences?
3. Based on the content in this chapter, suggest a plausible pathophysiological explanation for SCD in HCM.
4. Based on the case description, how thorough was the preparticipation screening given to John?
5. Under what circumstances might genetic screening for mutations be useful in evaluating the risk of HCM?