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ScienceDirect Journal of Electrocardiology xx (2015) xxx – xxx www.jecgonline.com
Review
Cardiac preparticipation screening for the young athlete: Why the routine use of ECG is not necessary William O. Roberts, MD, MS, a,⁎ Chad A. Asplund, MD, MPH, b Francis G. O'Connor, MD, MPH, c Steven D. Stovitz, MD, MS d a
d
University of Minnesota, 1414 Maryland Avenue East, St Paul, MN b Georgia Regents University, 300 E Hospital Rd, Augusta, GA c Uniformed Services of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD University of Minnesota, A682 Mayo Building, 420 Delaware Street SE, Minneapolis, MN
Abstract
The addition of an electrocardiogram (ECG) to the current United States athlete preparticipation physical evaluation (PPE) as a screening tool has dominated the PPE discussion over the past decade despite the lack of demonstrable outcomes data supporting the routine use of the diagnostic study for reduction of sudden cardiac death (SCD). A good screening test should influence a disease or health outcome that has a significant impact on public health and the population screened must have a high prevalence of the disease to justify the screening intervention. While SCD is publicly remarkable and like any death, tragic, the prevalence of SCD in young athletes is very low and the potential for false positive results is high. While ECG screening appears to have made an impact on SCD in Italian athletes, the strategy has made no impact on Israeli athletes, and the overall impact of ECG screening on American athletes is unclear. Until outcomes studies show substantial SCD reduction benefit, the addition of routine ECG PPE screening in young athletes should not be instituted. © 2015 Elsevier Inc. All rights reserved.
Keywords:
Preparticipation evaluation; PPE; Sudden cardiac death
Introduction The science, ethics, economics, and social factors that affect the routine incorporation of an electrocardiogram (ECG) screening to the current United States (US) preparticipation physical evaluation (PPE) have dominated the PPE content discussions over the past decade. This debate persists despite the lack of reliable ECG interpretation [1] or demonstrable outcomes data supporting the routine use of the diagnostic study for reduction of sudden cardiac death (SCD) across the athlete population. While it is clear that the ECG used in large groups of athletes will find cardiac abnormalities, some true and some false, it is not clear that the implementation of this potential prevention strategy will do more good than harm for young athletes in the United States. Historically, the US PPE guidelines have not endorsed routine ECG screening [2–4], nor have most other countries around the world beyond elite athletes [5]. The debate has been fueled by data from Italy showing a drop in the rate of SCD in athletes age 12–35 years old from 3.9 per 100,000 athlete years to 0.4 from 1979–81 to ⁎ Corresponding author at: University of Minnesota, 1414 Maryland Avenue East, St Paul MN 55106. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.01.010 0022-0736/© 2015 Elsevier Inc. All rights reserved.
2002–04, respectively, after implementing a legislatively mandated screening process that included a personal and family history, cardiac physical exam, and a 12 lead ECG [6]. Since there has been no presentation of SCD data from the years prior to 1979, it is unclear if the level of 3.9 SCD per 100,000 athlete-years was an accurate baseline or simply an elevated rate to do random variation (not elevated for a decade or more leading into the study), and it is impossible to determine if the ECG is the variable that is solely responsible for the rate reduction. The current SCD rate in Italian athletes is now half that of the unscreened non-athlete group, down approximately 4 fold from 1979–81 [6]. A similar mandated program was initiated in Israel where all athletes had personal and family history, CV related physical exam, a 12 lead ECG (annual), and a symptom limited stress testing (every 4 years from age 17 to 34) completed by physicians with certifications to perform the exam [7]. The SCD rate from the decade prior to the ECG screening program compared to the decade after initiating the program was unchanged [7]. In a study of young Italian athletes, the normal ECG had a high negative predictive value and was associated with a structurally normal heart in 95% of the cases [8]. However, the ECG is not a reliable screen as it has a high prevalence of “false positive” ECG abnormalities. In one study, only 10%
2
W.O. Roberts et al. / Journal of Electrocardiology xx (2015) xxx–xxx
of 145 athletes determined to have an abnormal screening ECG had echocardiographic evidence of structural cardiac disease or defect [8]. This study also showed poor sensitivity and specificity (51% and 61% respectively) of an abnormal ECG for the identification of cardiac abnormalities, and a very low (7%) positive predictive accuracy [8]. The ECG can identify some potentially lethal cardiac abnormalities, but the ECG will not detect any athletes with congenital coronary artery anomalies [9] nor detect all athletes with cardiomyopathies, channelopathies, or ventricular pre-excitation. In a screening of 32,652 unselected athletes, the prevalence of an abnormal ECG pattern was about 12%, with less than 5% showing decidedly abnormal patterns [10]. The accuracy and precision of ECG reading in athletes have been refined and education programs are available to improve ECG interpretation, however, a trained and skilled work force is not available in most parts of the world, including the US.
United States SCD rate in young athletes The SCD rate in the US is difficult to define. There is no uniform interpretation of what is included in the denominator (i.e. the number of persons at risk) or in the numerator (i.e. what is considered a “SCD”). The generally accepted definition of an exercise associated SCD is a death that occurs during or within an hour of completing exercise. However, some researchers include any athlete who dies of a cardiac cause even when the death occurs outside the confines of exercise creating a paradox for interpretation of the data. While deaths during physical activity, even during practices, are generally a part of the public record, sudden cardiac arrest with successful resuscitation may escape public awareness and be missed in studies of incidence and prevalence. There is no standardization with respect to including sudden cardiac arrest with successful resuscitation in the numerator so the capture of data is not as “simple” as SCA resulting in death. Even in a “closed” system like the Department of Defense, the leading cause of non-traumatic sudden death during exercise in individuals b age 35 years old is unfortunately unexplained [11]. Likewise, the denominator remains elusive. The National High School Federation data are often quoted as a denominator for high school sports participation, but this data collection is for athlete-seasons and does not reflect the actual number of athletes, as many athletes are involved in more than one sport per year. In Minnesota, there is a difference in number counts between Minnesota State High School League (MSHSL) high school varsity program athletes and middle school/high school athletes even though they span the same age range. For example, using the MSHSL high school varsity program unduplicated athlete years (tabulated annually since 1992) and catastrophic insurance data, the SCD rate from 1992 through 2012 school years during varsity program participation was 0.24, and in the last decade 0.1 per 100,000 athlete years [12]. Maron used an estimate of the same denominator for the time period of 1986–2011 along with deaths recorded in the US National Registry of Sudden Death in Athletes as the
numerator and calculated an SCD rate of 0.7 per 100,000 athlete-years [13]. But the 12 and 14 year old athletes who died may not have been in the schools’ varsity programs, which would require dropping them from the numerator or expanding the denominator to include all non-varsity program 7th, 8th, and 9th grade athletes, which could increase the denominator by double or more. The number of junior high/middle school athletes is not well known for Minnesota as the PPE is not required by junior high/middle school programs, which are not a part of the HS varsity programs, and the MSHSL catastrophic insurance plan does not cover that group of athletes. The same can be said for the study by Drezner and Harmon using the MSHSL varsity program denominator and taking the numerator from the Parent Heart Watch database, which resulted in an SCD rate of 0.65 per 100,000 athlete-years from 2003 to 2012 [14], but two of six deaths occurred away from sport and of the four that occurred during physical activity, three were not during varsity program activities (Personal communication, J Drezner). It is difficult to know if the denominator truly reflects the group at risk, as the true at risk denominator group may be considerably larger than the varsity program athletes. Of equal importance in this data set is the seven SCAs that occurred in athletes who were resuscitated and survived, three during MSHSL activities and four in other activities—one in the school classroom highlighting the need for on-site emergency response plans (Personal communication, J Drezner). At the college age level, Harmon et al. published the NCAA data for SCD in athletes at 2.3 per 100,000 athlete years, but the rate for those who meet the definition of death during activity was 1.4 or about half the publicized rate [15]. It is difficult to understand if this higher rate of SCD is due to better detection at the college level or to an age group that is higher risk than the high school age athletes. To summarize these data in a different perspective, the published Minnesota high school rates are 0.24, 0.7, and 0.7 deaths per 100,000 athlete-years using 3 different numerators and all using the same unduplicated MSHSL athletes denominator [12–14], and the NCAA college rates are 0.23 all cardiac deaths and 0.14 exercise related deaths per 100,000 athlete-years [15]. The average of these rates, 1 per 100,000 athlete-years compares to the Italian data of 0.4 and 0.8 per 100,000 person years in screened athletes and unscreened non-athletes respectively across the wider age range of 12 to 35 years old [6]. While it is clear that both consensus on numerator and denominator inclusion criteria and further study of SCA/SCD rates are needed; the rates quoted are essentially the same. While the rates may be off the mark by a factor of 2 or 3 to account for unknown successfully resuscitated SCA, differences in numerator inclusion criteria, or differences in the persons at risk denominator; the rates at each age level are certainly not off by a factor of 10 or 100. SCA and SCD are clearly low prevalence events in athletes. It is this very low prevalence of SCA and SCD that makes the ECG or any test without 100% sensitivity and specificity a questionable screening tool.
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False positives in ECG screening While it is accepted that an ECG can detect some cardiac abnormalities in high school and younger age athletes [16] and in previously screened college athletes [17], it is not clear that the addition of an ECG will change SCD outcomes or “do no harm” [3,4]. For example, a mathematical modeling of population risk and benefit using the Italian data applied to the UK athlete population concluded that a required ECG would be of more harm than benefit from a public health perspective, with a small impact on population health and a potentially great cost to athletes with unnecessary restriction of activity due to false positive findings [18]. The end result of the analysis demonstrated that preventing one SCD each year would exclude nearly 800 athletes from competition [18]. In addition, a number of screened athletes, whose tests were falsely negative, would die or suffer significant morbidity [18]. It does appear that some sub-populations are at greater risk and may potentially benefit from ECG screening (Table 1), but the death rates in these sub-populations need to be validated and better understood before requiring ECG screening in the spirit of “first do no harm.” Selective screening of sub-populations may raise ethical concerns and be viewed as either discriminatory or elitist by others, although elite national team and professional athletes are screened with ECGs in many countries [5]. The PPE Monograph is in its 4th edition and has been available for use in the US since the 1st edition in 1992 [2]. Despite the ready availability of the forms included in all editions of the monograph, states and colleges have been slow to adopt the standardized form [2]. Until there is universal use of the form, it will be difficult to determine if the addition of an ECG will truly affect outcomes and making the standardized form mandatory across the US is a logical first step in this process. Utilizing the currently recommended PPE question sets (syncope, family history, etc.) and physical exam aimed at SCD risk, as opposed to routinely screening all athletes with an ECG, will increase the likelihood that a positive ECG test will be a true positive for those who respond with a “yes” or those who have positive findings on physical exam. This use of an ECG as a case finding tool causes less harm across the population of athletes and reduces the portion of athletes who are unnecessarily restricted or have participation delayed by false positive studies. For a detailed comprehensive review of ECG screening for detection of cardiovascular disease in healthy 12–25 year old young people, the reader is referred to the 2014 American Heart Association–American College of Cardiology Scientific Statement [3]. A resting ECG can be helpful in detecting some, but not all, underlying heart abnormalities that put athletes at risk for SCD. Still, there are problems associated with the use of a resting ECG in the epidemiological, logistic, financial, and legal arenas. A major concern with the institution of ECG screening is that of false-positive tests. Many tests that are determined to be “positive” are in people who have no structural, morphological, electrophysiological or genetic pathology that puts them at extra risk for SCD. In order to
3
Table 1 Relative risk of athlete-related SCD by age, sex, intensity, and ethnicity of US and Italian athletes compared to the USA general population aged 15 to 24 years old. Population
Incidence RR (SCD/100,000 AY or */100,000 finishers)
Marathon Runners Female USA 1982–2009* 0.06 MSHSL Athletes MN 2003–2012 0.11 MSHSL Athletes MN 1993–2012 0.24 Italian Athletes 2001–2004 (Age 12–35) 0.43 Marathon Runners USA 2000–2010* 0.63 Minnesota HS Athletes 1986–2011 0.7 Italian Non-Athletes 1979–2004 0.79 NCAA Division III Athletes 1.05 NCAA Female Athletes 1.30 Marathon Runners USA 1982–2009* 1.30 NCAA Exertion Related SCD 1.37 King County WA Gen Pop (Age 14–24) 1.44 Italian Athletes 1979–2004 (Age 12–35) 1.9 US General Population (Age 15–24) 2.3 NCAA Athletes 2.33 NCAA Division II Athletes 2.38 NCAA Male Athletes 3.02 Marathon Runners Male USA 1982–2009* 3.4 NCAA Division I Athletes 3.45 Italian Athletes 1979–1981 (Age 12–35) 3.6 NCAA Division I Football Athletes 3.95 NCAA Black Athletes 5.65 NCAA Black Male Athletes 7.70 NCAA Division I Basketball 33.33
0.03 0.05 0.10 0.19 0.27 0.30 0.34 0.46 0.57 0.57 0.59 0.63 0.83 1.00 1.01 1.03 1.31 1.48 1.50 1.57 1.72 2.46 3.35 14.49
Reprinted with permission from Roberts WO et al., Curr Sports Med Rep. 13(6): 2014.
rectify this problem, there have been efforts to train physicians and to improve the interpretation of the athlete ECG. The theoretical reliability, sensitivity, and specificity of ECG have improved within the past several years as a result of consensus conferences aimed at focusing the criteria for distinguishing normal from abnormal ECGs in athletes [19–21]. A recent retrospective ECG analysis on the interpretation of ECG tracings in athletes has also helped with the interpretation of “normal” in trained athletes [22]. That being stated, the difficulty in discriminating normal from abnormal, even with the assistance of training and guidelines cannot be overstated. In a study performed by Magee et al., board certified specialists in a variety of disciplines were asked to scrutinize 85 validated electrocardiograms using guidelines from the European Society Criteria (ESC), blinded to the fact that 26 in the set were documented abnormal ECGs representing common causes of sudden death in young athletes [1]. The Cohen’s kappa coefficient across cardiology specialists was “substantial” and across primary care was “moderate” (0.69 vs 0.52, respectively, P b 0.001). Cohen's kappa coefficient is a statistical measure of inter-rater agreement and it is extremely important that experienced reviewers with the same background interpreting an ECG have comparable or ideally identical interpretations, which reflect study reliability. When screening for uncommon or rare entities, limited kappa introduces error and increases the rate of both false
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positives and false negatives studies. Clinician ECG interpretation in this study, according to the ESC interpretation criteria, appeared to demonstrate limited reliability and validity [1]. Furthermore, the medical system cannot prevent SCD in everyone who is correctly identified.
The Math The SCD range for MN high school athletes is between 2 and 7 per million athlete-years across 1–3 decades. Assume that this range is missing half of the cardiac arrests, the SCD events that are successfully resuscitated, and the SCA rate is about 17 per million athlete-years or about 1 in 60,000 athlete-years. How does the math work for screening a low incidence problem like sudden cardiac arrest with an ECG that has a 5% false positive rate? Table 2 outlines the positive predictive value (PPV) and the False Positives/True Positives (FP/TP), which is the number of subjects who require further screening for every athlete with SCD, utilizing a very low false-positive rate (FPR) of 5% and assuming no false-negative tests. Even at a prevalence of 1 SCD per 100 athlete years, approximately five of every six athletes with positive testing would still be “normal” and at no risk. As one can see, even in the theoretical scenario of perfect sensitivity and nearly perfect specificity, the incidence of SCD must be very high to avoid subjecting numerous individuals to unnecessary additional screening. Adding a mandatory ECG to our currently US screening process would occasionally save a life, but at the same time would give false reassurance to others who will still have undetected problems and cause harm to the many more with false positive results for this low prevalence condition. False positive tests may lead to financial strain on families and the medical system, iatrogenic harm, unnecessary and extended restriction from activity, psychological distress, and the diversion of resources from other public health related activities. A good screening test should influence a disease or health outcome that has a significant impact on public health, and an asymptomatic period where detection is possible with
Table 2 The influence of SCD incidence on number needed to screen (NNS) and positive predictive value (PPV) calculations assuming a 0% false negative test rate and a 5% false positive test rate where the false positive/true positive calculation equals the number of subjects who require further screening for every athlete with SCD. SCD per 105 AY
SCD per 106 AY
1 SCD per n AY
NNS
PPV
FP/TP
0.1 1.0 1.7 2.5 10.0 100.0 1000.0
1 10 17 25 100 1000 10,000
1,000,000 100,000 58,823 40,000 10,000 1000 100
1,000,000 100,000 58,823 40,000 10,000 1000 100
0.00002 0.0002 0.0003 0.0005 0.0020 0.0200 0.1680
49,999.95 4999.95 2941.13 1999.95 499.95 49.95 4.95
Abbreviations: SCD = Sudden Cardiac Deaths, AY = Athlete Years, n = Number, NNS = Number Needed to Screen to detect one SCD, PPV = Positive Predictive Value, FP/TP = False Positives/True Positive (i.e. number of subjects who require further screening for every SCD).
demonstrated long term outcomes improved by treatment in the asymptomatic period. The tool should be sufficiently sensitive, sufficiently specific, and acceptable to patients. And finally, the population screened must have a high prevalence of the disease to justify screening, the relevant medical care must be readily accessible and affordable, and patients must be willing to comply with the additional evaluation and treatment to modify the outcome of the underlying problem. Death from any cause is tragic and the nature of SCD in a young athlete is equally so. Where “screening” stops and where “diagnosis” starts can be ambiguous. A “diagnostic test” is done when someone has a symptom or sign, whereas a “screening test” is done in individuals with no symptoms or signs. Therefore, we would use the ECG as a diagnostic test for case finding in athletes who demonstrate something on history (e.g. family history of sudden cardiac death or personal history of syncope) or exam (e.g. worrisome murmur) as an initial step in evaluation. It could be argued that while publicly spectacular, the prevalence of SCD in athletes is very low, and medical care (cardiology follow-up) is not readily accessible for many. Other than disqualification from sports, there may not be a reasonable treatment (ie outcomes may not be improved), and patients may not be willing to comply with the disqualification from sports. However, it is crucial to remember that even the best efforts to train physicians will not greatly affect the very low predictive value for a positive test if the test is applied in low-risk populations (see Table 2). Therefore the addition of a mandatory ECG screening test to the current US PPE may not be helpful to the general or the athlete population, and indeed may cause unintended harms.
Conclusion Exertional sudden cardiac death is a tragic event that impacts not only the affected individual, but families, team members, coaches, medical providers, and communities. All efforts to mitigate these events including the implementation of early access to AEDs, emergency action plans, cardiopulmonary resuscitation certification training, improvements in preparticipation examination screening, and the appropriate utilization of technologies, including ECG, when indicated for those at risk for sudden death should be pursued. As sports medicine physicians committed to "do no harm", however, we question the implementation of technologies where the low prevalence of disease, the lack of reliability and the risk of false positives, create real challenges when assessing the benefit versus risk ratio. While ECG screening appears to have made an impact on SCD in Italian athletes, the strategy has made no difference on SCD rate in Israeli athletes, and at this point, the overall impact of ECG screening on American athletes is unclear, but would unnecessarily sideline many athletes. The addition of ECG screening in the US is not logical or practical at this time, considering the low prevalence of SCD, as the potential to do harm outweighs the benefits with respect to reductions in SCD. Until outcomes studies show both substantial
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benefit and improved reliability, the routine use of ECG screening for SCD reduction in young athletes should not be instituted. Acknowledgements This work was not supported by any grants. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Uniformed Services University, the US Army Medical Department or the Department of Defense. References [1] Magee C, Kazman J, Haigney M, Oriscello R, DeZee KJ, Deuster P, et al. Reliability and validity of clinician ECG interpretation for athletes. Ann Noninvasive Electrocardiol 2014;19(4):319–29. [2] Bernhardt DT, Roberts WO, editors. Preparticipation physical evaluation. 4th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2010. [3] Maron BJ, Friedman RA, Kligfield P, Levine BD, Viskin S, Chaitman BR, et al. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12–25 years of age): a scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 2014;64:1479–514. [4] Maron BJ, Thompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update. Circulation 2007;115:1643–55. [5] Roberts WO, Löllgen H, Matheson GO, et al. Advancing the preparticipation physical evaluation (PPE): an ACSM and FIMS joint consensus statement. Curr Sports Med Rep 2014;13(6):395–401. [6] Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006;291:1593–601. [7] Steinvil A, Chundadze T, Zeltser D, Rogowski O, Halkin A, Galily Y, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death: proven fact or wishful thinking? J Am Coll Cardiol 2011;57:1291–6. [8] Pelliccia A, Maron BJ, Culasso F, Di Paolo FM, Spataro A, Biffi A, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000;102:278–84.
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[9] Pelliccia A, Di Paolo FM, Quattrini FM, Basso C, Culasso F, Popoli G, et al. Outcomes in athletes with marked ECG repolarization abnormalities. N Engl J Med 2008;358:152–61. [10] Pelliccia A, Maron BJ, Culasso F, Di Paolo FM, Caselli G, Biffi A, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur Heart J 2007;28:2006–10. [11] Eckart RE, Shry EA, Burke AP, McNear JA, Appel DA, Castillo-Rojas LM, et al. Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance. J Am Coll Cardiol 2011;58:1254–61. [12] Roberts WO, Stovitz S. Incidence of sudden cardiac death in Minnesota high school athletes 1993–2012 screened with a standardized preparticipation evaluation. J Am Coll Cardiol 2013;62:1298–301. [13] Maron BJ, Haas T, Ahluwalia A, Rutten-Ramos SC. Incidence of cardiovascular sudden deaths in Minnesota high school athletes. Heart Rhythm 2013;10:374–7. [14] Drezner JA, Harmon KG, Marek JC. Incidence of sudden cardiac arrest in Minnesota high school student athletes: the limitations of catastrophic insurance claims. J Am Coll Cardiol 2014;63(14):1455–6. [15] Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation 2011;123:1594–600. [16] Fudge J, Harmon KG, Owens DS, Prutkin JM, Salerno JC, Asif IM, et al. Cardiovascular screening in adolescents and young adults: a prospective study comparing the Pre-participation Physical Evaluation Monograph 4th Edition and ECG. Br J Sports Med 2014;11(7):1190–4. [17] Baggish AL, Hutter Jr AM, Wang F, Yared K, Weiner RB, Kupperman E, et al. Cardiovascular screening in college athletes with and without electrocardiography. Ann Intern Med 2010;152(5):269–75. [18] Elston J, Stein K. Public health implications of establishing a national programme to screen young athletes in the UK. Br J Sports Med 2011;45:576–82. [19] Corrado D, Pelliccia A, Heidbuchel H, Sharma S, Link M, Basso C, Biffi A, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31(2):243–59. [20] Drezner JA, Ackerman MJ, Anderson J, Ashley E, Asplund CA, Baggish AL, et al. Electrocardiographic interpretation in athletes: the ‘Seattle Criteria’. Br J Sports Med 2013;47:122–4. [21] Uberoi A, Stein R, Freeman J, Wheeler M, Dewey F, Perez MV, et al. Interpretation of the electrocardiogram of young athletes. Circulation 2011;124:746–57. [22] Sheikh N, Papadakis M, Ghani S, Zaidi A, Gati S, Adami PE, et al. Comparison of electrocardiographic criteria for the detection of cardiac abnormalities in elite black and white athletes. Circulation 2014;129:1637–49.
ScienceDirect Journal of Electrocardiology xx (2015) xxx – xxx www.jecgonline.com
Review
Cardiac preparticipation screening for the young athlete: Why the routine use of ECG is not necessary William O. Roberts, MD, MS, a,⁎ Chad A. Asplund, MD, MPH, b Francis G. O'Connor, MD, MPH, c Steven D. Stovitz, MD, MS d a
d
University of Minnesota, 1414 Maryland Avenue East, St Paul, MN b Georgia Regents University, 300 E Hospital Rd, Augusta, GA c Uniformed Services of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD University of Minnesota, A682 Mayo Building, 420 Delaware Street SE, Minneapolis, MN
Abstract
The addition of an electrocardiogram (ECG) to the current United States athlete preparticipation physical evaluation (PPE) as a screening tool has dominated the PPE discussion over the past decade despite the lack of demonstrable outcomes data supporting the routine use of the diagnostic study for reduction of sudden cardiac death (SCD). A good screening test should influence a disease or health outcome that has a significant impact on public health and the population screened must have a high prevalence of the disease to justify the screening intervention. While SCD is publicly remarkable and like any death, tragic, the prevalence of SCD in young athletes is very low and the potential for false positive results is high. While ECG screening appears to have made an impact on SCD in Italian athletes, the strategy has made no impact on Israeli athletes, and the overall impact of ECG screening on American athletes is unclear. Until outcomes studies show substantial SCD reduction benefit, the addition of routine ECG PPE screening in young athletes should not be instituted. © 2015 Elsevier Inc. All rights reserved.
Keywords:
Preparticipation evaluation; PPE; Sudden cardiac death
Introduction The science, ethics, economics, and social factors that affect the routine incorporation of an electrocardiogram (ECG) screening to the current United States (US) preparticipation physical evaluation (PPE) have dominated the PPE content discussions over the past decade. This debate persists despite the lack of reliable ECG interpretation [1] or demonstrable outcomes data supporting the routine use of the diagnostic study for reduction of sudden cardiac death (SCD) across the athlete population. While it is clear that the ECG used in large groups of athletes will find cardiac abnormalities, some true and some false, it is not clear that the implementation of this potential prevention strategy will do more good than harm for young athletes in the United States. Historically, the US PPE guidelines have not endorsed routine ECG screening [2–4], nor have most other countries around the world beyond elite athletes [5]. The debate has been fueled by data from Italy showing a drop in the rate of SCD in athletes age 12–35 years old from 3.9 per 100,000 athlete years to 0.4 from 1979–81 to ⁎ Corresponding author at: University of Minnesota, 1414 Maryland Avenue East, St Paul MN 55106. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.01.010 0022-0736/© 2015 Elsevier Inc. All rights reserved.
2002–04, respectively, after implementing a legislatively mandated screening process that included a personal and family history, cardiac physical exam, and a 12 lead ECG [6]. Since there has been no presentation of SCD data from the years prior to 1979, it is unclear if the level of 3.9 SCD per 100,000 athlete-years was an accurate baseline or simply an elevated rate to do random variation (not elevated for a decade or more leading into the study), and it is impossible to determine if the ECG is the variable that is solely responsible for the rate reduction. The current SCD rate in Italian athletes is now half that of the unscreened non-athlete group, down approximately 4 fold from 1979–81 [6]. A similar mandated program was initiated in Israel where all athletes had personal and family history, CV related physical exam, a 12 lead ECG (annual), and a symptom limited stress testing (every 4 years from age 17 to 34) completed by physicians with certifications to perform the exam [7]. The SCD rate from the decade prior to the ECG screening program compared to the decade after initiating the program was unchanged [7]. In a study of young Italian athletes, the normal ECG had a high negative predictive value and was associated with a structurally normal heart in 95% of the cases [8]. However, the ECG is not a reliable screen as it has a high prevalence of “false positive” ECG abnormalities. In one study, only 10%
2
W.O. Roberts et al. / Journal of Electrocardiology xx (2015) xxx–xxx
of 145 athletes determined to have an abnormal screening ECG had echocardiographic evidence of structural cardiac disease or defect [8]. This study also showed poor sensitivity and specificity (51% and 61% respectively) of an abnormal ECG for the identification of cardiac abnormalities, and a very low (7%) positive predictive accuracy [8]. The ECG can identify some potentially lethal cardiac abnormalities, but the ECG will not detect any athletes with congenital coronary artery anomalies [9] nor detect all athletes with cardiomyopathies, channelopathies, or ventricular pre-excitation. In a screening of 32,652 unselected athletes, the prevalence of an abnormal ECG pattern was about 12%, with less than 5% showing decidedly abnormal patterns [10]. The accuracy and precision of ECG reading in athletes have been refined and education programs are available to improve ECG interpretation, however, a trained and skilled work force is not available in most parts of the world, including the US.
United States SCD rate in young athletes The SCD rate in the US is difficult to define. There is no uniform interpretation of what is included in the denominator (i.e. the number of persons at risk) or in the numerator (i.e. what is considered a “SCD”). The generally accepted definition of an exercise associated SCD is a death that occurs during or within an hour of completing exercise. However, some researchers include any athlete who dies of a cardiac cause even when the death occurs outside the confines of exercise creating a paradox for interpretation of the data. While deaths during physical activity, even during practices, are generally a part of the public record, sudden cardiac arrest with successful resuscitation may escape public awareness and be missed in studies of incidence and prevalence. There is no standardization with respect to including sudden cardiac arrest with successful resuscitation in the numerator so the capture of data is not as “simple” as SCA resulting in death. Even in a “closed” system like the Department of Defense, the leading cause of non-traumatic sudden death during exercise in individuals b age 35 years old is unfortunately unexplained [11]. Likewise, the denominator remains elusive. The National High School Federation data are often quoted as a denominator for high school sports participation, but this data collection is for athlete-seasons and does not reflect the actual number of athletes, as many athletes are involved in more than one sport per year. In Minnesota, there is a difference in number counts between Minnesota State High School League (MSHSL) high school varsity program athletes and middle school/high school athletes even though they span the same age range. For example, using the MSHSL high school varsity program unduplicated athlete years (tabulated annually since 1992) and catastrophic insurance data, the SCD rate from 1992 through 2012 school years during varsity program participation was 0.24, and in the last decade 0.1 per 100,000 athlete years [12]. Maron used an estimate of the same denominator for the time period of 1986–2011 along with deaths recorded in the US National Registry of Sudden Death in Athletes as the
numerator and calculated an SCD rate of 0.7 per 100,000 athlete-years [13]. But the 12 and 14 year old athletes who died may not have been in the schools’ varsity programs, which would require dropping them from the numerator or expanding the denominator to include all non-varsity program 7th, 8th, and 9th grade athletes, which could increase the denominator by double or more. The number of junior high/middle school athletes is not well known for Minnesota as the PPE is not required by junior high/middle school programs, which are not a part of the HS varsity programs, and the MSHSL catastrophic insurance plan does not cover that group of athletes. The same can be said for the study by Drezner and Harmon using the MSHSL varsity program denominator and taking the numerator from the Parent Heart Watch database, which resulted in an SCD rate of 0.65 per 100,000 athlete-years from 2003 to 2012 [14], but two of six deaths occurred away from sport and of the four that occurred during physical activity, three were not during varsity program activities (Personal communication, J Drezner). It is difficult to know if the denominator truly reflects the group at risk, as the true at risk denominator group may be considerably larger than the varsity program athletes. Of equal importance in this data set is the seven SCAs that occurred in athletes who were resuscitated and survived, three during MSHSL activities and four in other activities—one in the school classroom highlighting the need for on-site emergency response plans (Personal communication, J Drezner). At the college age level, Harmon et al. published the NCAA data for SCD in athletes at 2.3 per 100,000 athlete years, but the rate for those who meet the definition of death during activity was 1.4 or about half the publicized rate [15]. It is difficult to understand if this higher rate of SCD is due to better detection at the college level or to an age group that is higher risk than the high school age athletes. To summarize these data in a different perspective, the published Minnesota high school rates are 0.24, 0.7, and 0.7 deaths per 100,000 athlete-years using 3 different numerators and all using the same unduplicated MSHSL athletes denominator [12–14], and the NCAA college rates are 0.23 all cardiac deaths and 0.14 exercise related deaths per 100,000 athlete-years [15]. The average of these rates, 1 per 100,000 athlete-years compares to the Italian data of 0.4 and 0.8 per 100,000 person years in screened athletes and unscreened non-athletes respectively across the wider age range of 12 to 35 years old [6]. While it is clear that both consensus on numerator and denominator inclusion criteria and further study of SCA/SCD rates are needed; the rates quoted are essentially the same. While the rates may be off the mark by a factor of 2 or 3 to account for unknown successfully resuscitated SCA, differences in numerator inclusion criteria, or differences in the persons at risk denominator; the rates at each age level are certainly not off by a factor of 10 or 100. SCA and SCD are clearly low prevalence events in athletes. It is this very low prevalence of SCA and SCD that makes the ECG or any test without 100% sensitivity and specificity a questionable screening tool.
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False positives in ECG screening While it is accepted that an ECG can detect some cardiac abnormalities in high school and younger age athletes [16] and in previously screened college athletes [17], it is not clear that the addition of an ECG will change SCD outcomes or “do no harm” [3,4]. For example, a mathematical modeling of population risk and benefit using the Italian data applied to the UK athlete population concluded that a required ECG would be of more harm than benefit from a public health perspective, with a small impact on population health and a potentially great cost to athletes with unnecessary restriction of activity due to false positive findings [18]. The end result of the analysis demonstrated that preventing one SCD each year would exclude nearly 800 athletes from competition [18]. In addition, a number of screened athletes, whose tests were falsely negative, would die or suffer significant morbidity [18]. It does appear that some sub-populations are at greater risk and may potentially benefit from ECG screening (Table 1), but the death rates in these sub-populations need to be validated and better understood before requiring ECG screening in the spirit of “first do no harm.” Selective screening of sub-populations may raise ethical concerns and be viewed as either discriminatory or elitist by others, although elite national team and professional athletes are screened with ECGs in many countries [5]. The PPE Monograph is in its 4th edition and has been available for use in the US since the 1st edition in 1992 [2]. Despite the ready availability of the forms included in all editions of the monograph, states and colleges have been slow to adopt the standardized form [2]. Until there is universal use of the form, it will be difficult to determine if the addition of an ECG will truly affect outcomes and making the standardized form mandatory across the US is a logical first step in this process. Utilizing the currently recommended PPE question sets (syncope, family history, etc.) and physical exam aimed at SCD risk, as opposed to routinely screening all athletes with an ECG, will increase the likelihood that a positive ECG test will be a true positive for those who respond with a “yes” or those who have positive findings on physical exam. This use of an ECG as a case finding tool causes less harm across the population of athletes and reduces the portion of athletes who are unnecessarily restricted or have participation delayed by false positive studies. For a detailed comprehensive review of ECG screening for detection of cardiovascular disease in healthy 12–25 year old young people, the reader is referred to the 2014 American Heart Association–American College of Cardiology Scientific Statement [3]. A resting ECG can be helpful in detecting some, but not all, underlying heart abnormalities that put athletes at risk for SCD. Still, there are problems associated with the use of a resting ECG in the epidemiological, logistic, financial, and legal arenas. A major concern with the institution of ECG screening is that of false-positive tests. Many tests that are determined to be “positive” are in people who have no structural, morphological, electrophysiological or genetic pathology that puts them at extra risk for SCD. In order to
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Table 1 Relative risk of athlete-related SCD by age, sex, intensity, and ethnicity of US and Italian athletes compared to the USA general population aged 15 to 24 years old. Population
Incidence RR (SCD/100,000 AY or */100,000 finishers)
Marathon Runners Female USA 1982–2009* 0.06 MSHSL Athletes MN 2003–2012 0.11 MSHSL Athletes MN 1993–2012 0.24 Italian Athletes 2001–2004 (Age 12–35) 0.43 Marathon Runners USA 2000–2010* 0.63 Minnesota HS Athletes 1986–2011 0.7 Italian Non-Athletes 1979–2004 0.79 NCAA Division III Athletes 1.05 NCAA Female Athletes 1.30 Marathon Runners USA 1982–2009* 1.30 NCAA Exertion Related SCD 1.37 King County WA Gen Pop (Age 14–24) 1.44 Italian Athletes 1979–2004 (Age 12–35) 1.9 US General Population (Age 15–24) 2.3 NCAA Athletes 2.33 NCAA Division II Athletes 2.38 NCAA Male Athletes 3.02 Marathon Runners Male USA 1982–2009* 3.4 NCAA Division I Athletes 3.45 Italian Athletes 1979–1981 (Age 12–35) 3.6 NCAA Division I Football Athletes 3.95 NCAA Black Athletes 5.65 NCAA Black Male Athletes 7.70 NCAA Division I Basketball 33.33
0.03 0.05 0.10 0.19 0.27 0.30 0.34 0.46 0.57 0.57 0.59 0.63 0.83 1.00 1.01 1.03 1.31 1.48 1.50 1.57 1.72 2.46 3.35 14.49
Reprinted with permission from Roberts WO et al., Curr Sports Med Rep. 13(6): 2014.
rectify this problem, there have been efforts to train physicians and to improve the interpretation of the athlete ECG. The theoretical reliability, sensitivity, and specificity of ECG have improved within the past several years as a result of consensus conferences aimed at focusing the criteria for distinguishing normal from abnormal ECGs in athletes [19–21]. A recent retrospective ECG analysis on the interpretation of ECG tracings in athletes has also helped with the interpretation of “normal” in trained athletes [22]. That being stated, the difficulty in discriminating normal from abnormal, even with the assistance of training and guidelines cannot be overstated. In a study performed by Magee et al., board certified specialists in a variety of disciplines were asked to scrutinize 85 validated electrocardiograms using guidelines from the European Society Criteria (ESC), blinded to the fact that 26 in the set were documented abnormal ECGs representing common causes of sudden death in young athletes [1]. The Cohen’s kappa coefficient across cardiology specialists was “substantial” and across primary care was “moderate” (0.69 vs 0.52, respectively, P b 0.001). Cohen's kappa coefficient is a statistical measure of inter-rater agreement and it is extremely important that experienced reviewers with the same background interpreting an ECG have comparable or ideally identical interpretations, which reflect study reliability. When screening for uncommon or rare entities, limited kappa introduces error and increases the rate of both false
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positives and false negatives studies. Clinician ECG interpretation in this study, according to the ESC interpretation criteria, appeared to demonstrate limited reliability and validity [1]. Furthermore, the medical system cannot prevent SCD in everyone who is correctly identified.
The Math The SCD range for MN high school athletes is between 2 and 7 per million athlete-years across 1–3 decades. Assume that this range is missing half of the cardiac arrests, the SCD events that are successfully resuscitated, and the SCA rate is about 17 per million athlete-years or about 1 in 60,000 athlete-years. How does the math work for screening a low incidence problem like sudden cardiac arrest with an ECG that has a 5% false positive rate? Table 2 outlines the positive predictive value (PPV) and the False Positives/True Positives (FP/TP), which is the number of subjects who require further screening for every athlete with SCD, utilizing a very low false-positive rate (FPR) of 5% and assuming no false-negative tests. Even at a prevalence of 1 SCD per 100 athlete years, approximately five of every six athletes with positive testing would still be “normal” and at no risk. As one can see, even in the theoretical scenario of perfect sensitivity and nearly perfect specificity, the incidence of SCD must be very high to avoid subjecting numerous individuals to unnecessary additional screening. Adding a mandatory ECG to our currently US screening process would occasionally save a life, but at the same time would give false reassurance to others who will still have undetected problems and cause harm to the many more with false positive results for this low prevalence condition. False positive tests may lead to financial strain on families and the medical system, iatrogenic harm, unnecessary and extended restriction from activity, psychological distress, and the diversion of resources from other public health related activities. A good screening test should influence a disease or health outcome that has a significant impact on public health, and an asymptomatic period where detection is possible with
Table 2 The influence of SCD incidence on number needed to screen (NNS) and positive predictive value (PPV) calculations assuming a 0% false negative test rate and a 5% false positive test rate where the false positive/true positive calculation equals the number of subjects who require further screening for every athlete with SCD. SCD per 105 AY
SCD per 106 AY
1 SCD per n AY
NNS
PPV
FP/TP
0.1 1.0 1.7 2.5 10.0 100.0 1000.0
1 10 17 25 100 1000 10,000
1,000,000 100,000 58,823 40,000 10,000 1000 100
1,000,000 100,000 58,823 40,000 10,000 1000 100
0.00002 0.0002 0.0003 0.0005 0.0020 0.0200 0.1680
49,999.95 4999.95 2941.13 1999.95 499.95 49.95 4.95
Abbreviations: SCD = Sudden Cardiac Deaths, AY = Athlete Years, n = Number, NNS = Number Needed to Screen to detect one SCD, PPV = Positive Predictive Value, FP/TP = False Positives/True Positive (i.e. number of subjects who require further screening for every SCD).
demonstrated long term outcomes improved by treatment in the asymptomatic period. The tool should be sufficiently sensitive, sufficiently specific, and acceptable to patients. And finally, the population screened must have a high prevalence of the disease to justify screening, the relevant medical care must be readily accessible and affordable, and patients must be willing to comply with the additional evaluation and treatment to modify the outcome of the underlying problem. Death from any cause is tragic and the nature of SCD in a young athlete is equally so. Where “screening” stops and where “diagnosis” starts can be ambiguous. A “diagnostic test” is done when someone has a symptom or sign, whereas a “screening test” is done in individuals with no symptoms or signs. Therefore, we would use the ECG as a diagnostic test for case finding in athletes who demonstrate something on history (e.g. family history of sudden cardiac death or personal history of syncope) or exam (e.g. worrisome murmur) as an initial step in evaluation. It could be argued that while publicly spectacular, the prevalence of SCD in athletes is very low, and medical care (cardiology follow-up) is not readily accessible for many. Other than disqualification from sports, there may not be a reasonable treatment (ie outcomes may not be improved), and patients may not be willing to comply with the disqualification from sports. However, it is crucial to remember that even the best efforts to train physicians will not greatly affect the very low predictive value for a positive test if the test is applied in low-risk populations (see Table 2). Therefore the addition of a mandatory ECG screening test to the current US PPE may not be helpful to the general or the athlete population, and indeed may cause unintended harms.
Conclusion Exertional sudden cardiac death is a tragic event that impacts not only the affected individual, but families, team members, coaches, medical providers, and communities. All efforts to mitigate these events including the implementation of early access to AEDs, emergency action plans, cardiopulmonary resuscitation certification training, improvements in preparticipation examination screening, and the appropriate utilization of technologies, including ECG, when indicated for those at risk for sudden death should be pursued. As sports medicine physicians committed to "do no harm", however, we question the implementation of technologies where the low prevalence of disease, the lack of reliability and the risk of false positives, create real challenges when assessing the benefit versus risk ratio. While ECG screening appears to have made an impact on SCD in Italian athletes, the strategy has made no difference on SCD rate in Israeli athletes, and at this point, the overall impact of ECG screening on American athletes is unclear, but would unnecessarily sideline many athletes. The addition of ECG screening in the US is not logical or practical at this time, considering the low prevalence of SCD, as the potential to do harm outweighs the benefits with respect to reductions in SCD. Until outcomes studies show both substantial
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benefit and improved reliability, the routine use of ECG screening for SCD reduction in young athletes should not be instituted. Acknowledgements This work was not supported by any grants. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Uniformed Services University, the US Army Medical Department or the Department of Defense. References [1] Magee C, Kazman J, Haigney M, Oriscello R, DeZee KJ, Deuster P, et al. Reliability and validity of clinician ECG interpretation for athletes. Ann Noninvasive Electrocardiol 2014;19(4):319–29. [2] Bernhardt DT, Roberts WO, editors. Preparticipation physical evaluation. 4th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2010. [3] Maron BJ, Friedman RA, Kligfield P, Levine BD, Viskin S, Chaitman BR, et al. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12–25 years of age): a scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 2014;64:1479–514. [4] Maron BJ, Thompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update. Circulation 2007;115:1643–55. [5] Roberts WO, Löllgen H, Matheson GO, et al. Advancing the preparticipation physical evaluation (PPE): an ACSM and FIMS joint consensus statement. Curr Sports Med Rep 2014;13(6):395–401. [6] Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006;291:1593–601. [7] Steinvil A, Chundadze T, Zeltser D, Rogowski O, Halkin A, Galily Y, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death: proven fact or wishful thinking? J Am Coll Cardiol 2011;57:1291–6. [8] Pelliccia A, Maron BJ, Culasso F, Di Paolo FM, Spataro A, Biffi A, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000;102:278–84.
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