The literature review evaluates the studies that have been done on sudden cardiac arrest/death among the young athletes. Hypertrophie cardiomyopathy (HCM) will be discussed as part of the literature review because it is one of the major causes of SCD in the United States.
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Nevertheless, other causes of SCD will be mentioned. Of importance, the literature review will help identify the current state of knowledge and practice on HCM and sudden cardiac death among the young athletes in general.
There has been heated debate in the literature about the importance of screening athletes before their participation in competitive sports (pre-participation screening). Most recently, recommendations have been made to include electrocardiography (ECG) in the screening program.
The literature review will look at both sides of the debate by highlighting the benefits of the screening protocol as well as the pitfalls. Special focus will be on ECG, which has been said to improve the efficacy of screening. Studies that have been done on pre-participation screening will be discussed.
The studies chosen for the literature review are drawn mainly from the United States, Italy, Japan and other European countries. By examining the experiences of these countries in pre-participation screening, the literature review will help to highlight similarities and differences in the outcomes of PPS across countries and the reasons behind them.
Most importantly, the literature review will propose the way forward both in terms of what measures should be taken when screening young athletes before their involvement in competitive sports as well as the implications of the findings on primary care.
Definition and etiology of hypertrophie cardiomyopathy (HCM)
Sudden cardiac arrest (SCA) or sudden cardiac death (SCD) is brought about by a number of cardiac diseases that generally can be categorized into structural cardiovascular abnormalities (for example, cardiomyopathies) and primary cardiac electrical diseases (for example ion channel disorders) (Corrado, Migliore, Basso & Thiene, 2006).
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Hypertrophie cardiomyopathy (HCM) is the most common structural and functional disorder linked to sudden cardiac deaths among children and young adults. HCM is an inherited intrinsic disease of the myocardium characterized by left ventricular hypertrophy without chamber dilatation, in the absence of either a systemic or other cardiac disease, which may cause a similar magnitude of hypertrophy.
In many cases, HCM is a clinically silent disease (Hughes, 2004). Several studies have suggested that HCM is the leading cause of SCD in young athletes in the United States, contributing to almost thirty percent of the incidences (Maron, 2003).
Although some patients with HCM may present with symptoms (for instance chest pain, syncope, or exertional lightheadedness) (Adabag, Kuskowski & Maron, 2006), studies show that 80% of athletes who die from HCM have no warning signs prior to their deaths (36).
The majority (75%) of patients with HCM also lack identifiable murmurs on cardiac auscultation. As a result, identifying patients with HCM by history and physical examination alone is ineffective (Drezner, Berger & Campbell, 2010).
Clinical course of HCM
Maron (2002) argues that “hypertrophic cardiomyopathy is unique among cardiovascular diseases because of its potential for clinical presentation during any stage of life (from infancy to more than ninety years of age)” (p. 1309).
Even if serious clinical outcomes have been known for several years, especially SCA, a more accepted view pertaining to prognosis has evolved recently. In the past, there were misperceptions about the clinical significance of HCM mainly due to its comparatively low prevalence in the cardiac populations, extreme heterogeneity, and uneven patterns of patient referral that brought about important selection biases (Maron, 2002).
As a result, the risks of HCM seemed to have been overestimated by reliance on often-cited worrying annual mortality rates of 3% to 6%. “These figures, which are based mainly on biased tertiary-center experience, have contributed significantly to the misguided perception that HCM is a generally inauspicious disorder,” (Maron, 2002, p. 1311).
Recent reports show that the annual rate of death caused by HCM is much lower (approximately 1%) than what was reported in the past. Such data offer a more balanced view in which HCM may be linked with important symptoms and premature death but more frequently with no or relatively mild disability and normal life expectancy (Maron, 2002).
The pathology of HCM
HCM is characterized macroscopically by left ventricular hypertrophy, which may be asymmetrical or symmetrical. The classical anatomic form of HCM, described by Teare in 1958 (cited in Hughes, 2004), entailed thickening of the basal anterior septum, which bulges underneath the aortic valve and leads to the narrowing of the left ventricular outflow tract (Hughes, 2004).
There is concomitant anterior displacement of the papillary muscles and the mitral leaflets with coaptation occurring in the body of the leaflets rather than at the tips. During systolic contraction, the part of the anterior leaflet distal to the coaptation point is subject to Venturi and/or drag forces leading to systolic anterior motion (SAM) of the mitral valve and mitral leaflet–septal contact.
All these factors in effect destroy the left ventricular outflow tract before systole reaches completion, thereby leading to subaortic impediment. The SAM of the anterior leaflet of the mitral valve is linked to the failure of coaptation of the anterior and posterior mitral valve leaflets and the onset of mitral regurgitation, which is directed posteriorly into the left atrium (Hughes, 2004).
With the passage of time, endocardial fibrosis occurs over the septum immediately subjacent to the aortic valve, causing a subaortic mitral impact lesion to form. This lesion is an exact mirror image of the anterior cusp of the mitral valve and chordae and is characterized by a sharp lower edge, which corresponds to the lower border of the valve cusp.
Diffuse endocardial thickening is not a specific feature of HCM and may occur in abnormal hearts with diverse etiologies. The repeated mitral leaflet–septal contact causes mechanical trauma, consequently the valve leaflets and chordae tendineae become thickened by fibrosis and there is a small but significant risk of chordal rupture and bacterial endocarditis (Towbin, 2000).
Diagnosis of HCM and other causes of sudden cardiac death
Pre-participation screening of young athletes
Although it does not occur frequently, the demise of a young athlete while participating in a competitive sport is catastrophic and leads to public and media attention. Indeed, in comparison with the risk of sudden death in the general population, the risk of sudden death (SD) in sports persons is very low, with a rate of 1 event per 100,000 athletes annually in the United States.
In Italy, the incidence rate has been estimated at 3 in every 100,000 athletes (Corrado, Basso, Schiavon, Pelliccia & Thiene, 2008). The difference in the incidence rates between the countries is attributed to differences in the athletes’ population with the US population having younger and more female athletes than the Italian population. The risk of SD increases with age and is more common among male athletes.
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There are various causes of SD and include: hypertrophic cardiomyopathy (HCM), right ventricular cardiomyopathy, myocarditis and Marfan syndrome. The causes of SD vary from one region to another, with HCM more common in the United States, right ventricular cardiomyopathy more common in Italy and myocarditis more common in Germany and Marfan syndrome more common in China (Pigozzi, Spataro, Fagnani & Maffilli, 2012).
The cause of sudden death also varies with age; with severe coronary artery disease as the common cause among people under the age of 35. Sudden death is therefore triggered by underlying cardiovascular disorders together with physical strain hence the need for screening of athletes before their participation in any sport.
The purpose of pre-participation screening
Screening of physically-competitive adolescents and young adults to identify the risk of sudden death originated in the early 1970’s. Over the years, recommendations, guidelines and policy statements on preparticipation screening of athletes have been developed and amended (Chaitman, 2007).
Studies focusing on the causes and prevention of sudden cardiac deaths of young athletes have also been conducted in different countries such as Italy, Japan and the United States. Prior to this evolution, screening was targeted at high school athletes and mainly focused on non-cardiovascular screening.
Pre-participation screening (PPS) for cardiovascular disorders has been widely recommended by various medical and sporting societies such as the American Heart Association (AHA), the European Society of Cardiology (ESC) and the International Olympic Committee. PPS is viewed as a strategy for preventing SD by identifying cardiac pathology in competitive athletes.
The PPS is a tool for early identification of structural cardiac diseases linked with SD as well as for minimizing the risk of the advancement of diseases that may arise from vigorous athletic training and competition. AHA also states that the main goal of PPS is to minimize the cardiovascular risks associated with strenuous physical activity as well as increase the safety of athletic participation.
The American College of Cardiology also argues that “the eventual objective of PPS is to detect the silent cardiovascular abnormalities that can lead to sudden death” (Asif & Drezner, 2012, p. 446). Because of the increasing number of older men taking part in competitive sports, the PPS should reduce the occurrence of deadly cardiac arrests by highlighting the health risks of the participants.
PPS involves both taking the medical history of the participant and undertaking a physical medical examination. Despite its perceived benefits in preventing sports-related SD, there is heated debate about the efficacy of PPS with or without electrocardiography (ECG).
The debate surrounding pre-participation screening with ECG
Arguments in favor of the efficacy of pre-participation screening revolve around its link to reduced mortality among young athletes. A number of studies have been conducted to support PPS but the inclusion of electrocardiography (ECG) in the PPS remains uncertain. Corrado et al. (2012) conducted a study in Italy to determine the effectiveness of the pre-participation screening in young athletes.
The researchers argue that an efficient PPS test should identify majority of individuals with underlying cardiovascular disorders although minimal error is allowed. Screening protocol based only on medical history and physical examination is bound to fail because majority of the cardiovascular conditions that trigger SD in young athletes are silent and highly likely to be undetected and misdiagnosed.
Corrado et al. (2012) studied the Italian screening program which includes not only medical history and physical examination but also electrocardiography (ECG). The program was started in 1982 and is known to increase the probability of identifying athletes who have symptoms of underlying heart disorders.
Data show that “of 33,735 athletes who have gone through the screening program, 8.9% were referred for additional tests, mainly echocardiography, while 621 were disqualified from participating in their sports due to cardiovascular-related reasons” (Corrado et al., 2012, p. 1597).
A further 82% of 22 athletes showed abnormal ECG results during the PPS. On the contrary, only 23% were identified to be at risk following a medical history and physical examination protocol. This shows that ECG is indeed more effective than medical history and physical examination alone (Corrado et al., 2012).
The role of ECG in identifying athletes at risk of sudden cardiac arrest has also been studied by Vetter (2009). The researcher reported studies on ECG screening of children and young athletes in different countries such as Japan, Italy, Europe, and the United States.
There are significant variations in the use of ECG across countries. In Japan for instance, mass screening of children for cardiovascular diseases using ECG has been in place since the early 1970’s. The program has proved to be effective in identifying children with underlying heart problems. In the United States, the screening of young athletes using ECG was found to have 70% sensitivity compared to only 6% sensitivity for history and physical examination.
The use of ECG among the Nevada High School athletes helped to identify athletes suffering from severe cardiovascular abnormalities. Despite the efficacy of ECG, medical history and physical examination remain the most widely used tools for screening athletes. This protocol is limited because of inconsistencies among the medical personnel and forms across different states (Vetter, 2009).
Baggish et al. (2010) carried out a study on college athletes to determine the efficacy of ECG in PPS by comparing PPS with ECG and PPS without ECG over three consecutive years. The screening involved medical history, physical examination, 12-lead ECG and trans-thoracic echocardiography (TTE).
The inclusion of ECG into the screening program helped to detect abnormalities in 10 of the 11 athletes who had TTE-detected abnormalities. The other participant had mitral valve prolapsed and no associated high-risk features that required sports restriction. Most importantly, the combination of medical history, physical examination and ECG helped to identify three participants with abnormalities that necessitated sports restriction.
On the contrary, the use of only medical history and physical examination identified only one of these participants. In total, the ECG-inclusive screening program had a sensitivity of 90.9%, a specificity of 82.7%, a positive predictive value of 10.4%, and a negative predictive value of 99.8% (Baggish et al., 2010). This study provides proof of the efficacy of ECG as compared to only medical history and physical examination.
Asif and Drezner (2012) also support the inclusion of ECG in a pre-participation screening program. The researchers however argue that the efficacy of ECG is only high if modern standards for interpretation of the results are used.
The researchers reviewed several studies such as Baggish et al. (2012) who based their study on college athletes. The use of ECG increased the sensitivity to detect cardiac abnormalities by 46%. However, there was a high false-positive rate of 16% but this rate was reduced to 9% after the modern ECG standards were applied.
The objection to the use of ECG-inclusive screening revolves around the high false-positive rate associated with ECG. It has been argued that such high false-positive rates have led to unnecessary additional medical evaluations and exemptions of athletes from competitive athletic activities.
Indeed, some studies on ECG (for instance, Asif & Drezner, 2012) showed ECG abnormalities in almost 40% of participants, leading to the dismissal of the tool by many physicians. However, the high false-positive rate of ECG is largely affected by the interpretation criteria adopted by individual physicians (Drezner et al., 2010).
New standards have therefore been developed to enhance the ability of physicians to differentiate between physiologic cardiac adaptation in athletes and results indicative of inherent cardiac pathology.
Drezner et al. (2010) argue that there is need for uniformity in the terminologies used to describe ECG results among athletes. Many of the ECG variations that physicians used to refer to as abnormal “are presently recognized as physiologic and part of benign cardiac adaptation in athletes (otherwise referred to as athlete’s heart)” (Drezner et al., 2010, p. 89).
Physicians interpreting ECG results need to know the common training-associated ECG alterations, which are normal. On the other hand, “training-unrelated ECG variations indicate the possibility of underlying pathology and require further diagnostic tests.” (Drezner et al., 2010, p. 89)
The implementation of the new standards in various studies has shown lower false-positive rates associated with ECG. For instance, Wilson, Basavarajaiah and Whyte (2008) studied the results of an ECG-inclusive screening program in the United Kingdom. The results had a false-positive rate of 3.7% with only 1.9% of the false-positive caused by the ECG. In the Corrado et al. (2012) study, the false-positive rate was only 2.5%.
Arguments against using ECG for screening are also based on the inability of ECG to detect all types of disorders that predispose athletes to sudden cardiac death. For instance, ECG cannot detect premature coronary artery disease, yet this disorder accounts for almost 20% of all causes of SCD in young athletes. In addition, ECG lacks the ability to identify aortic root disorders and may fail to identify almost 5% of HCM patients (Asif & Drezner, 2012).
The cost-effectiveness issue of including ECG in a pre-participation screening is yet another reason for the controversy surrounding ECG-inclusive PPS (Wheeler, Heidenreich, Froelicher, Hlatky & Ashley, 2010). The costs associated with the PPS range from direct cost of undertaking the ECG, cost of additional tests if positive results are found and indirect individual costs that arise from disqualification from competitive sports.
The issue of cost has inspired a number of cost-effectiveness analyses. Researchers argue that unlike older athletes, the young athletes still have a long life ahead of them. Any intervention that prevents a potential sudden death is therefore likely to enable the athletes survive many years with normal life expectancy.
A cost effectiveness analysis study that measured the cost per the number of years saved show that an ECG-inclusive screening leads to a cost of $42,000 per year of life saved. This cost is less than the $50,000 cost-effectiveness threshold allowed for a health intervention (Corrado et al., 2011).
Other direct costs involve the cost of training specialized physicians and development of the necessary infrastructure. All these costs add to the burden that is placed on the entire healthcare system of a country as a result of including ECG in the pre-participation screening of athletes.
The false-positive rate associated with ECG-inclusive PPS also leads to indirect costs to individual athletes especially if there are unnecessary disqualifications of athletes from competitive sports. Such false-positive results may cost individual athletes their profession thereby leading to discontentment in life.
Womak (2011) argues that the cost-effectiveness of ECG-inclusive PPS may be enhanced if the risk of sudden death is stratified. Some populations have a higher risk of sudden cardiac death than others, for instance, the risk is higher among college athletes than high school athletes. Moreover, the risk of SCD also varies with the type of sport.
The risk is higher in sports such as football and basketball because of the intensity of physical activity in these sports. The researcher calls for additional research to be conducted to examine the disparities in the risk of SCD between sports. Womak (2011) argues that ECG should be applied to populations and sports with increased risk of SCD so as to enhance the cost effectiveness of the tool.
ECG and hypertrophic cardiomyopathy (HCM)
In the United States, hypertrophic cardiomyopathy (HCM) is the leading cause of SD among the young competitive athletes.
Echocardiography is the most effective tool for recognizing HCM but the fact that it is expensive and impractical for diagnosing a large population led to the proposal of using twelve-lead ECG as an alternative diagnostic tool (Corrado et al., 2005).
ECG is said to be cost-effective and practical for screening a large population. The Italian study mentioned earlier provided proof of the effectiveness of using ECG to detect cardiovascular problems such as HCM among the young athletes.
In a follow-up study of the athletes who had been identified as having HCM in the Italian study, it was found that none of them died eight years later because they were disqualified from competitive sports, which in turn reduced their risk of death (Corrado et al., 2005).
The prevalence rate of HCM among non-athletes was found to be similar in Italy and the United States, according to a study conducted by Burke et al. (cited in Corrado et al., 2005). However, there were differences in the HCM-related death rates among the athletes between these two countries, with Italy reporting lower rates than the US.
The reason given is that Italian athletes go through a mandatory screening that involves ECG before participation and those who fail the test are disqualified from competing. On the other hand, the American athletes only go through medical history and physical examinations (Corrado et al., 2005).
Limitations of history and physical-based screening
A screening program that only includes medical history and physical examination is limited in various ways. The major challenge in using this approach is that apparently healthy athletes with no symptoms of heart problems may indeed have unsuspected cardiovascular diseases.
Whereas sudden death is usually the first manifestation of a cardiac disorder in almost 80 percent of young athletes, few of these victims had any signs and symptoms of an underlying cardiovascular disorder (Asif & Drezner, 2012).
Although the efficacy of such a screening has not been widely studied, the few studies that exist show that a screening program based on only medical history and physical examination has a lower sensitivity to detect cardiovascular abnormalities at risk for SCD.
For instance, in the study by Maron, Shirani and Poliac (1996), 158 American trained athletes had died of SCD out of which 134 had underlying cardiovascular abnormalities. Unfortunately only 3% of these athletes had been suspected of having cardiovascular diseases during the pre-participation screening.
In 1996 and later reaffirmed in 2007, the American Heart Association recommended PPS of competitive athletes, which includes 12 components of personal history, family history and physical examinations. In spite of the limited sensitivity of this protocol, the use of a comprehensive questionnaire to guide the screening has not been widely adopted and the guidelines used are often inadequately implemented (Asif & Drezner, 2012).
Some countries, like the United States, allow the PPS to be conducted by non-physicians with little training in cardiovascular health. Only 81% of the states use AHA-recommended questionnaires.
Recommended protocol of pre-participation cardiovascular screening
The recommended procedure for cardiovascular screening of athletes before engaging in a competitive sport includes completion of personal and family history, undertaking a physical examination followed by ECG. The evaluation should be done by physicians with specialized training, skills and cultural background effective in accurately identifying the clinical symptoms and signs related to cardiovascular diseases that trigger sports-related SD.
In countries such as Italy, there are sports medical specialists whose work is to periodically evaluate the health of the athletes. The screening should start at the beginning of the competitive athletes’ activity, which is approximately 12-14 years. The screening should also be done regularly so as to diagnose the development of any heart disorder early on.
Most of the conditions that trigger sports-related sudden deaths are genetically determined. It is therefore important to study the family history of the athlete.
A positive family history is identified if a close relative has experienced a premature heart attack or sudden death or if there is a history of cardiomyopathy, Marfan syndrome, long QT syndrome, severe arrhythmias, and coronary artery disease among other conditions.
A personal history is also considered positive if the person has experienced exertional chest pain or discomfort, irregular heart beat or palpitations, extreme fatigue, and shortness of breath (Corrado et al., 2005).
Positive physical results include musculoskeletal and ocular features suggestive of Marfan syndrome, slower and delayed femoral artery pulses, mid- or end-systolic clicks, a second heart sound single or widely split and fixed with respiration, marked heart murmurs (any diastolic and systolic grade ≥ 2/6), irregular heart rhythm, and brachial blood pressure > 140/90 mmHg (on >1 reading) (Corrado et al., 2005).
A 12-lead ECG is considered to be positive in the presence of various conditions such as HCM, myocarditis, myocardial bridge, pulmonary thrombo-embolism, dilated cardiomyopathy, mitral valve prolapsed, dissecting aortic aneurysm and anomalous origin of coronary artery, among others (Corrado et al., 2005).
Participants with positive results at basal assessment need to be referred for additional non-invasive tests such as echocardiography, 24-hour ambulatory Holter monitoring, and exercise testing. If there is uncertainty about these latter tests, further invasive tests such as coronary angiography, endomyocardial biopsy, contrast ventriculography and electrophysiological study should be done.
If these tests reveal that the subjects may be affected by cardiovascular conditions that may trigger sports-related sudden death the subjects should be disqualified from any competitive athletic activity (Corrado et al., 2005).
Trends in sudden cardiac deaths after pre-participation screening
To provide evidence of the effectiveness of pre-participation screening in reducing sports-related deaths, Corrado et al. (2012) examined the trends in sudden cardiac deaths among young athletes between 1979 and 2004. The participants included both athletes and non-athletes aged between the ages of 12 and 35 residing in the Veneto region of Italy.
The researchers performed a trend analysis of the annual incidence rates and causes of sudden cardiac death in the sporty population and compared them with the rates in the non-sporty population. They also studied the temporal link between mortality and regular PPS which was introduced in the country in 1982.
During the period of study, a total of 55 cases of SDC were reported in the screened athletic population, giving an incidence rate of 1.9 deaths per 100000 person-years.
Of the 55 victims of SCD, 50 were male and 5 were female. “44 of the cases took place during the sports activity while the remaining 6 happened immediately after the activity” (Corrado et al., 2012, p. 1598). Nevertheless, the number and incidence rates of SCD declined significantly over the years. For instance, between 1979 and 1980 the annual rate of SCD was 3.6 per 100000 person-years.
This rate declined to 0.43 per 100000 person-years between 2001 and 2004 (Corrado et al., 2012). The decline in the annual SCD rates is attributed to the introduction of PPS in 1982. Indeed, the decline in the SCD rates between the early screening period and the late screening period was significant (63%).
On the other hand, the trend in the SCD rates in the unscreened non-athletic population remained comparatively the same during the entire period of study. This study lends support to the role played by pre-participation screening in preventing sudden cardiac deaths among athletes.
Conclusion and implications of PPS for primary care
The results from the studies reviewed above have important implications for primary care. Implementing a preparticipation screening program that encompasses medical history, physical examination and electrocardiography is a potent tool in identifying the at-risk athletes thereby reducing sudden cardiac deaths among the athletes population (Asif & Drezner, 2012).
Nevertheless, there is a need to reevaluate the current guidelines to include the routine use of ECG screening. The Italian experience shows that such a program is not only effective in detecting underlying cardiac disorders responsible for triggering sudden cardiac deaths, but it can also be implemented on a large-scale.
Although PPS does not fully meet the World Health Organization’s criteria for screening because of SCD’s low incidence rate, the body recognizes diseases with potentially serious prognoses for screening and SCD is among them. The pre-participation screening of athletes should be done by highly-qualified, trained and specialized physicians with the skills and expertise to detect abnormalities from screening results.
The modern standards of interpreting the results should be implemented to avoid unnecessary further tests and disqualifications from competitive sports. To address the issue of cost, utilizing more trained nurse practitioners rather than physicians to conduct the PPS would be help reduce the cost burden associated with including ECG into a pre-participation screening program (Morse & Funk, 2012).
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