Cardiovascular Assessment for Risk of Sudden Cardiac Death in Athletes

Abstract

In classical literature, a hero is always larger than life, does extraordinary things, and performs deeds most people think impossible. A hero makes people proud of being human or a member of a community because he has redefined human nature in a slightly larger way. Today's athletes often assume that role. Young competitive athletes are widely regarded as a special subgroup of healthy individuals with a unique life-style who are seemingly invulnerable and often capable of extraordinary physical achievement. However, occasionally, one of these extraordinary individuals dies suddenly and unexpectedly. When this occurs, we begin to question the safety of vigorous exercise and whether a way exists to recognize these at-risk athletes earlier.Physical inactivity is recognized as a risk factor for coronary artery disease. The U.S. Department of Health & Human Services (21) issued the 2008 Physical Activity Guidelines for Americans, which states that most health benefits occur with at least 150 min per week of moderate intensity physical activity (brisk walking), 75 min per week of vigorous activity (jogging), or a combination of the two. Additional benefits occur with more physical activity. However, participation in exercise is associated with a small but finite increase in risk for sudden cardiac death (SCD). In this review, SCD is defined as death occurring within 1 h of participation in sports (1). The risk of SCD among young athletes is found in Table 1 (17,20,22). Compared to rest, vigorous exercise, defined as >6 METs (19) (where 1 MET approximates seated oxygen uptake of 3.5 mL·kg−1·min−1), results in a very small (0.01% or less) and transient increase in risk of SCD. However, the overwhelming health benefits derived from chronic exercise training outweigh this increase risk of mortality.Intense and repetitive exercise leads to physiologic changes in the heart, manifested as hypertrophy of the left ventricle, bradycardia, and supra-normal performance that can result in ECG changes. These changes are referred to as Athlete's Heart Syndrome (16). Congenital or inherited heart diseases are also associated with changes in heart structure and conduction, such as hypertrophy of the right and left ventricles, arrhythmias, and abnormalities of repolarization. These congenital changes affecting the ECG are often difficult to differentiate from the Athlete's Heart Syndrome, even with additional testing. Rarely does an athlete who harbors an undetected congenital or inherited cardiac disorder die suddenly during a sporting event. This is always dramatic and unexpected.This review of SCD is divided into two parts. First, we discuss the detection of athletes with congenital or inherited heart disease who are at increased risk for SCD. Secondly, we discuss what recommendations can be made about participation in vigorous exercise and competitive sports once the diagnosis is made.A goal is to identify participants in sporting events at risk for SCD. In the United States there are 10 to 12 million athletes participating in competitive sports at the high school, college, and professional sport levels (8,9,12). It is estimated that between 0.02% and 0.07%, or about 30,000, of these competitive athletes have congenital or inherited heart disease that can cause SCD. Most of these athletes are asymptomatic. The following is a discussion of the experience in the United States, Italy, and Israel in detecting those athletes at risk for SCD, a discussion of cost-benefit of such a program, and possible alternative approaches to the athlete at risk for SCD.The cause of SCD in athletes depends on the athlete's age. Athletes over age 35 yr are considered leisure-time athletes. They generally participate in such individual sports as running, cycling, or swimming, and the cause of their SCD is typically coronary artery disease (CAD). Athletes under age 35 yr often take part in organized sports and are considered competitive athletes; they participate in such team sports as football or basketball. The cause of SCD in these athletes is typically congenital and inherited cardiac disease. Table 2 presents the frequency distribution of the congenital and inherited cardiac diseases in athletes (9).The risk of SCD in athletes during exercise depends on the type of cardiac disease. Those with asymptomatic CAD receive a protective effect from regular exercise. Exercise results in a decreased sympathetic tone, increased vagal tone, improvement in cardiovascular risk factors, and decreased platelet function. Athletes with congenital or inherited cardiac diseases are also at risk for SCD with sports activity. However, unlike athletes with CAD, they increase their risk for SCD each time they exercise; thus, over time, exposure to sport activity actually increases the risk for SCD in competitive athletes.A difference in opinion exists depending on whether you are an athlete in the United States, Europe, or Israel regarding the best screening practices to detect an increased risk of SCD. The 2007 American Heart Association (AHA) Scientific Statement (12) proposed a 12-point screening procedure based on personal history, family history, and physical examination, which is referred to as the preparticipation exam (PPE) (Table 3). However, the sensitivity of the PPE for detecting potential causes of SCD is only 40% to 50%. Thus, 50% to 60% of those with potential SCD causes may go undetected if the PPE is used. Glover and Maron (5) reported on their experience with 134 athletes who experienced SCD after having undergone a PPE. Only 3% of the athletes were suspected of having cardiovascular disease, less than 1% received correct diagnosis, and none were disqualified from competitive sports. Today, we have many tests that can help identify those athletes with heart disease who are at risk for SCD. Does it make sense to include some or all of these tests in the PPE?In Italy, the difference in the PPE is the result of the Medical Protection of Athletic Activities Law that was passed in 1971 (15). This law requires every citizen engaged in official competitive sport activities to successfully pass periodic preventive examinations, which include a 12-lead ECG. These examinations are to be performed by physicians who have completed a 4 yr program in sports medicine and sports cardiology. Corrado et al. (2) published their 30 yr experience in Italy with the PPE, which included an ECG. They showed a reduction of the annual incidence of SCD from 4.2 per 100,000 person-years in 1979 to 0.9 per 100,000 person-years in 2004. This was identical to the risk of the non-exercising public (Table 4). Based on this single report from Italy, the 2005 European Society of Cardiology (3) and the 2004 International Olympic Committee (6) recommend that an ECG be part of the PPE.In 2009, Maron et al. (10) published a comparison of the US and Italian experiences with SCD in young competitive athletes. The state of Minnesota in the United States and the Veneto region in Italy have comparable sizes for general population and for athletes. Between 1993 and 2004, the incidence of SCD was 12 deaths in Veneto and 11 deaths in Minnesota. Between 1979 and 2004, 55 people died in Veneto over 26 yr and 22 people died in Minnesota over 23 yr. This suggests an unusually high rate of SCD in Veneto athletes when Corrado et al. (2) started recording SCD in Italian athletes (Table 4).US and Italian experiences with the PPE have been critiqued in the literature. The US data on SCD represents retrospective data collected from media reports and insurance claims. Critics state that this data underestimates the magnitude of the problem. Also, in the United States, the athletes are younger (12 to 24 yr; mean 16 yr) and only 65% are male.The Italian report is also retrospective, with the data regarding SCD systematically gathered because all athletes are registered participants in the national screening program. However, the athletes are older (12 to 35 yr; mean 23 yr) and more likely to be male (85%) than those in the United States and as such represent a higher risk group for SCD. Also, one could question whether the reduction in the rate of SCD noted by the Italians is due to the ECG or is it due to the training of the screening physicians, the standardization of the ECG interpretation (Table 5), or perhaps due to the algorithms for the work up and return to competitive sports?Until recently, controversy about whether the ECG should be added to the PPE was based entirely on a single study. In 2011, Steinvil et al. (18) reported on data from Israel. In 1995–1996, an unusually high incidence of SCD in young competitive athletes occurred, and similar to the Italians, the Israelis enacted the National Sports Law in 1997, which mandated an ECG and stress testing as part of the PPE. Twenty-four deaths or cardiac arrests were documented in competitive athletes between 1985 and 2009. Eleven deaths occurred before the National Sports Law was enacted in 1997, and 13 deaths occurred after that time. They concluded that the addition of the ECG to the PPE does not decrease the incidence of SCD in young competitive athletes (Table 4).In 2011, Magalski (7) published data from the University of Kansas screening of 964 consecutive college athletes by using PPE and ECGs. Two hundred and twenty (22.8%) athletes had abnormal PPEs. Three hundred and thirty-four (35%) athletes had abnormal ECGs, of which 95 (10%) were distinctly abnormal. Of the athletes with distinctly abnormal ECGs, 76% had normal PPE and 24% had abnormal PPEs. The sensitivity was improved with the addition of an ECG to the PPE; however, the positive predictive value, negative predictive value, and specificity were essentially unchanged (Table 6).The cost of a program to perform mandatory ECG screening in athletes is not insignificant. There are 10 million middle school and high school athletes. At $75 for a PPE, the cost would be $750 million. It is projected that 1.5 million athletes would have an abnormal PPE, requiring additional testing at $500, or an additional $750 million. Administrative costs also need to be included. The 2007 AHA Scientific Statement projects that the entire program could cost up to $2 billion annually (12). In 2010, Wheeler et al. (23) evaluated the cost-effectiveness of an ECG plus PPE compared to the PPE alone for preparticipation screening. They compared the incremental health care cost per life-year gained between competitive athletes in high school and college (14 to 22 yr) by using three different screening scenarios: no screening, PPE only, and PPE plus ECG. They determined that the addition of an ECG to the PPE saves 2.06 life-years per 100 athletes at an incremental total cost of $89 per athlete and yields a cost-effectiveness ratio of $42,000 per life-year saved (95% CI $21,200, $71,300 per life-year saved) compared to the PPE alone. For comparison, it is generally accepted that interventions (such as kidney dialysis) that cost <$50,000 per yr are reasonable.Finally, Bayes's Theorem states that the predictive accuracy of a test depends not only on the sensitivity and specificity of the test but also on the pretest probability of disease in the population being tested. For a screening test to be successful, the pretest likelihood of disease being tested for should be 20% to 80% and the sensitivity and specificity near 100%. This is unfortunately not the case when detecting heart disease in young athletes. If a test to identify heart disease in athletes has a specificity of 99% and a sensitivity of 99% (a near-perfect test, which the ECG is not) and the pretest probability of disease is only 0.2% to 0.7%, the false positive rate will far exceed the true positive rate. This is the case for ECG assessment in young athletes. Out of the 200,000 athletes undergoing PPE with an ECG, there will be 2,000 abnormal ECGs, but only one athlete will actually have a cardiac condition that can cause SCD (Table 7).It may even be that the wrong question is being asked. While screening for congenital and inherited heart disease is important, maybe no amount of testing will uncover all athletes at risk for SCD. Another approach to this issue would be to make sure that automated external defibrillators (AEDs) are available in all sports venues. Drezner et al. (4) reported on the use of AEDs at NCAA Division I universities. During surveillance, 35 episodes of SCD were reported. However, only 5 (14%) of the reported episodes were in collegiate athletes. The remaining 30 (86%) occurred in spectators, coaches, officials, and students (nonathletes) who happened to be in the building for other reasons. Nineteen of the 35 episodes of SCD were resuscitated for an overall resuscitation rate of 54%. In the five cases of SCD in inter-collegiate athletes, none were successfully resuscitated. Why the athletes did not respond to resuscitation is unclear. Perhaps the number of episodes of SCD in athletes is too small at this point in time to draw a conclusion or perhaps there is something unique about the pathophysiology of SCD in athletes during vigorous activity that makes it more difficult to resuscitate an athlete. Additional studies documenting the experience of AEDs in athletes with SCD are necessary to know their role in the treatment of SCD in athletes.The recommendations of the European Society of Cardiology (3) and the International Olympic Committee (6) to include the ECG as part of the PPE are based on one study: the Italian experience as reported by Corrado et al. (2). The recommendations of the ACC/AHA Guidelines (12) do not include an ECG as part of the PPE. No one recommends an echocardiogram as part of the PPE. The recently reported Israeli study by Steinvil et al. (18) supports the ACC/AHA recommendation, which does not include an ECG. Finally, the disqualification of a skilled athlete from participating in vigorous sport because of a misdiagnosis cannot be taken lightly. All recommendations to date are based on retrospective studies, and the US and Israeli studies have been criticized for possibly underestimating the incidence of SCD in athletes. This controversy will continue until a well-designed prospective study is undertaken to answer the question of what should be included in the PPE.Once the athlete with congenital heart disease is identified, what are his or her restrictions? Are all competitive sports banned? Or is this dependent on the type of congenital heart problem and the type of sport? The 36th Bethesda Conference (13), sponsored by the American College of Cardiology Foundation, was convened in New Orleans in 2004 to attempt to answer these questions. At this conference, a “classification of sports” (14) was devised that is based on peak dynamic and static components achieved during competition (Figure 1). For the current discussion, sports that have high dynamic component (>70% V˙O2) or high static component (>50% maximal voluntary contraction) or both are considered vigorous.The Bethesda conference initially identified general cardiac lesions that always represent a contraindication to participating in high intensity sport (Table 8). Those athletes with such mechanical devices as pacemakers and defibrillators are excluded from all sports. The conference attendees then reviewed the available literature for each specific congenital, inherited, and acquired heart lesion and made recommendations about which sports those athletes with these conditions could and could not participate. The specific inherited or acquired cardiac lesions discussed included hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, channelopathies, acquired and congenital valvular heart, disease of the aorta, and acquired and congenital coronary artery disease. Unfortunately, most of the recommendations are expert opinions and not based on randomized controlled trials.Using the athlete with a bicuspid aortic valve as an example, the first question to be asked during an assessment should be “Does the athlete have aortic stenosis?” If yes, then the decision of participation depends on the degree of stenosis present. Thus, the athlete can participate in all competitive sports and undergo yearly evaluations if the stenosis is mild but should not participate in competitive sports if the stenosis is severe. Athletes with moderate stenosis can participate competitively in low-intensity sports. Knowing that the bicuspid aortic valve is frequently associated with an aortopathy, the second question should be “What is the diameter of the aorta?” Athletes with bicuspid aortic valves that are only mildly stenotic and have an ascending aorta diameter of <40 mm can participate in all competitive sports. If the aorta diameter is 40 to 45 mm, the athlete can participate in low to moderate static and dynamic sports but should avoid contact sports because of their potential for trauma leading to dissection of the enlarged aorta.At this time, decisions on what should be included in the PPE is controversial and additional studies are needed to determine if an ECG added to the PPE identifies additional athletes at risk of SCD. Once the diagnosis of heart disease is made, the 36th Bethesda Conference Eligibility Recommendations for Competitive Athletes With Cardiovascular Disorders is a very helpful document to make decisions about who should be disqualified from sport and to determine the level of vigorous activity in which they can be allowed to participate.