Lessons Learned from Preparticipation Cardiovascular Screening in a State Funded Program

Lessons Learned from Preparticipation Cardiovascular Screening in a State Funded Program Ilana Zeltser, MDa,*, Bryan Cannon, MDb,c, Lawrence Silvana, MD, PhDb,d, Arnold Fenrich, MDd, Jayni George, RNa, Jessica Schleifer, MPHe, Michelle Garcia, MHEe, Aliessa Barnes, MDa, Shannon Rivenes, MDb, Hanoch Patt, MDd, George Rodgers, MDe, and William Scott, MDa In 2007, the Texas legislature appropriated money for a pilot study to evaluate cardiovascular screening of student athletes to identify those who might be at risk of sudden death using a questionnaire, physical examination, electrocardiography, and limited echocardiography. We sought to determine (1) the feasibility of a state-wide cardiovascular screening program, (2) the ability to reliably identify at-risk subjects, and (3) problems in implementing screening state wide. The data were analyzed using established pediatric electrocardiographic and echocardiographic criteria. Positive results were confirmed by a blinded reviewer. In 31 venues (2,506 students), the electrocardiographic findings met the criteria for cardiovascular disease in 57 (2.3%), with 33 changes suggestive of hypertrophic cardiomyopathy, 14 with long QT syndrome, 7 with Wolff–Parkinson–White syndrome, and 3 with potential ischemic findings related to a coronary anomaly. Of the 2,051 echocardiograms, 11 had findings concerning for disease (9 with hypertrophic cardiomyopathy and 1 with dilated cardiomyopathy). In patients with electrocardiographic findings consistent with hypertrophic cardiomyopathy, the limited echocardiograms were normal in 24 of 33. Of the 33 who remained at risk of sudden death on the electrocardiogram or echocardiogram, 25 (65.8%) pursued the recommended evaluation, which confirmed long QT syndrome in 4, Wolff–Parkinson–White syndrome in 7, and dilated cardiomyopathy in 1. The interobserver agreement was 100% for electrocardiography and 79% for echocardiography. The questionnaire identified 895 (35% of the total) potentially at-risk students, with disease confirmed in 11 (1.23%). In conclusion, in this large state-funded project, electrocardiographic and echocardiographic screening identified 11 of 2,506 patients potentially at risk of cardiovascular disease. The questionnaire was of limited value and had a large number of false-positive results. Interobserver variation was significant for echocardiography and might create problems with limited echocardiographic screening. Finally, many subjects with abnormal screening results declined a follow-up evaluation. © 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:902–908) Considerable national interest is being focused on developing more effective preparticipation screening programs to identify those student athletes who might be at risk of sudden death (SD). The challenge in developing such a screening process is that one must take into account the extraordinary number of young athletes and the infrequency of SD. The purpose of the present study was to analyze the results of statewide screening of young athletes for undiagnosed causes of SD. The factors analyzed included technical

a University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas, Texas; bBaylor College of Medicine and Texas Children’s Hospital, Houston, Texas; cMayo Clinic, Rochester, Minnesota; d Children’s Cardiology Associates, Austin, Texas; and eChampionship Hearts Foundation, Austin, Texas. Manuscript received April 6, 2012; revised manuscript received and accepted May 1, 2012. This project was funded by RFP number 701-08-027 from the Texas Education Agency (Austin, Texas). Presented at the American Heart Association Scientific Sessions 2010, Chicago, Illinois. *Corresponding author: Tel: (214) 456-6333; fax: (214) 456-6154. E-mail address: [email protected] (I. Zeltser).

0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2012.05.018

and operational limitations in both the performance and the coordination of such a program, appropriate identification of screen-positive subjects, and the ability to perform all aspects of the screening in a timely and cost-effective manner.

Methods In 2007, the Texas State legislature approved Senate Bill 7, relating to the placement of automated external defibrillators in schools statewide. Section 38.109 of this bill allocated 1 million dollars for the Texas Education Agency to “establish a pilot program under which students are administered cardiovascular screening, including an electrocardiogram and an echocardiogram.” To implement this screening program, a collaborative group of investigators was formed with regional centers in Dallas, Austin, and Houston. The University of Texas Southwestern Medical School and Baylor College of Medicine institutional review boards approved the study. Student athletes from grades 6 to 12 were enrolled from 34 schools in the Dallas area, 27 schools in the Austin area, and 10 schools in the Houston area. The inclusion www.ajconline.org

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Figure 1. Screening process. Determined by the geographic logistics of the event, the students were screening according to 1 of 2 models. UIL ⫽ University Interscholastic League. ECG ⫽ electrocardiogram; HC ⫽ hypertrophic cardiomyopathy; SD ⫽ sudden death. Table 1 Criteria for abnormal screening electrocardiograms (ECGs) requiring additional evaluation Rate ⬍40 or ⬎125 beats/min QRS axis ⬎120° (right-axis deviation) QRS axis ⱕ30° (left-axis deviation) Right atrial enlargement, left atrial enlargement QRS ⬎120 ms (right bundle branch block, left bundle branch block, or interventricular conduction delay) First-degree atrioventricular block ⬎200 ms Second- or third-degree atrioventricular block “Brugada pattern” in lead V1 Wolff–Parkinson–White syndrome

Ventricular premature complexes ⱖ3 per 6-second tracing Ventricular couplets/triplets Any supraventricular tachycardia ST-T wave abnormality in ⱖ2 leads* Abnormal Q wave (⬎0.04 s or ⬎3 mm deep in ⱖ2 leads)

Corrected QT interval ⬎450 ms QS pattern in ⱖ2 precordial leads Modified left ventricular hypertrophy criteria† Poor R wave progression

* ST-T wave abnormality included primarily inverted T waves but also ⬎2-mm ST-segment depression; isolated T-wave inversion in lead aVR or lead V1 was not considered abnormal. † Modified left ventricular hypertrophy criteria included increased precordial voltage (⬎3 mV) plus increased limb lead voltage as determined by the standards of Davignon31 or increased precordial lead voltage (⬎3 mV) accompanied by ST-T–wave abnormalities, prominent Q waves, extreme left-axis deviation (ⱖ30°), or findings of left atrial enlargement. Criteria modified from Corrado et al.2– 4

criteria required all students to (1) participate in either school and/or recreational sport teams, (2) complete the screening questionnaire (in accordance with the 12 currently recommended American College of Cardiology/American Heart Association screening guidelines),1 and (3) provide informed consent and student assent. Those with pre-existing cardiovascular conditions were excluded from the present study.

Students underwent screening according to 1 of 2 models, depending on their location. In both models, students underwent 12-lead electrocardiography (Figure 1). In model 1, all students underwent limited 2-dimensional echocardiography, and then the electrocardiograms (ECGs) and echocardiograms were reviewed off-site. In model 2, the 12-lead ECG was interpreted by an on-site pediatric electrophysiologist. If concern was present for cardiomyopathy, the student underwent a limited echocardiographic study. A screen-positive ECG or echocardiogram specifically referred to the identification of the potential risk of having disease abnormalities that could result in a future life-threatening event, thereby prompting a referral to a pediatric cardiologist for additional evaluation. Previously established screening electrocardiographic criteria (Table 1) were used to identify those at risk of SD.2–7 In this athletic population, an electrocardiographic diagnosis of left ventricular hypertrophy was made using recent modifications described by Corrado et al,3,4 including increased QRS voltage in the precordial leads associated with additional nonvoltage criteria such as left atrial enlargement, left axis deviation, ST-segment and T-wave abnormalities, and pathologic Q waves. The ECGs were visually assessed for the presence of Wolff–Parkinson–White (WPW) pattern. All borderline QT values were measured manually in lead II or V5, and the corrected QT interval was calculated using Bazett’s formula. Athletes with corrected QT values of ⱖ450 ms were referred for a comprehensive assessment. All ECGs were interpreted by board-certified pediatric cardiologists with a specialty in electrophysiology. If an ECG was screen positive (i.e., hypertrophic cardiomyopathy [HC], long QT [LQT] syndrome, WPW), the students were advised not to participate in competitive athletics and to be examined by a pediatric cardiologist. Incidental findings on the ECG were recorded but not considered screen positive. These findings included PACs/ PVCs and incomplete right bundle branch block. The limited screening echocardiogram was a focused 2-dimensional study to assess for the presence of HC using

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Table 2 Criteria for abnormal screening echocardiogram requiring additional evaluation Variable

Left ventricular mass (g) Left ventricular mass/body surface area (g/m2) Ventricular septal thickness (cm) Left ventricular posterior wall thickness (cm)

Women Reference Range

Mildly Abnormal

Moderately Abnormal

67–162 43–95

163–186 96–108

187–210 109–121

0.6–0.9 0.6–0.9

1.0–1.2 1.0–1.2

1.3–1.5 1.3–1.5

Men Severely Abnormal ⱖ211 ⱖ122 ⱖ1.6 ⱖ1.6

Reference Range

Mildly Abnormal

Moderately Abnormal

88–224 49–115

225–258 116–131

259–292 132–148

0.6–1.0 0.6–1.0

1.1–1.3 1.1–1.3

1.4–1.6 1.4–1.6

Severely Abnormal ⱖ293 ⱖ149 ⱖ1.6 ⱖ1.6

Data modified from American Society of Echocardiography Committee recommendations.8

Figure 2. Subject population. (Left) Demographic profile of the students screened. (Right) Various sport disciplines in which students were engaged.

standard criteria recommendations from the American Society of Echocardiography (Table 2).8 Apical and parasternal views were obtained, and the left ventricular (LV) enddiastolic, LV end-systolic, interventricular septal dimension in diastole, LV posterior wall end-diastolic dimension, LV ejection fraction, and LV shortening fraction were measured. Where appropriate, the measurements were adjusted according to the body surface area. Students whose results were screen positive were not given sports clearance and were referred for directed, standard care by a pediatric cardiologist. Students with an incidental, nonlife-threatening abnormality appreciated on the echocardiographic screen, including atrial septal defect, bicuspid aortic valve, and mitral valve prolapse, were not excluded from participation but were directed to follow-up with a pediatric cardiologist. In model 1, all results were communicated, at a later date, verbally and by a letter to the parents. In model 2, the students received a report at the screening venue. Abnormal screen results were also communicated at a later date, both verbally and in writing, to the parents. Three facilities in Dallas, Austin, and Houston performed the initial electrocardiographic and echocardiographic interpretation. Each facility had board-certified pe-

diatric cardiologists with expertise in electrophysiology conduct the electrocardiographic analysis. Pediatric cardiologists with expertise in echocardiography and an Intersocietal Commission for the Accreditation of Echocardiographic Laboratories designation were responsible for the echocardiographic interpretation. To control for interobserver variability, all positive results were sent to 1 of the other 2 facilities for blinded validation. Also, 10% of all normal results were sent to a second facility for blinded validation. In cases in which disease was suspected by the primary facility but considered normal by the review facility, the records were sent in a blinded fashion to an independent institution for interpretation of the results. This was a prospective, nonrandomized, observational study. The demographic data are presented as mean ⫾ SD. With respect to the cost analysis, the expenses reported are related to the screening process only. Results A total of 28 events were present for model 1, averaging 72.2 students/event. On average, the ECGs were interpreted 82.5 days after the screening venue, the echocardiograms

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Figure 3. Follow-up results of screening 12-lead ECG. Of 57 students with abnormalities on screening ECG concerning for SD, 22 pursued recommended follow-up, with disease ultimately diagnosed in 9. DC ⫽ dilated cardiomyopathy; ECG ⫽ electrocardiogram; HC ⫽ hypertrophic cardiomyopathy; LQT ⫽ long QT; WPW ⫽ Wolff Parkinson White syndrome.

Figure 4. Follow-up results of screening 2-dimensional echocardiogram. Of 14 screening echocardiograms concerning for potential SD, 8 subjects pursued recommended the follow-up, with disease ultimately diagnosed in 4. Subjects denoted with an asterisk have been treated by their primary cardiologist with concern for disease; however none of these 3 were considered by 2 blinded reviewers in our study to have met the echocardiographic criteria for disease diagnosis on either the screening or the more comprehensive follow-up echocardiographic study. DC ⫽ dilated cardiomyopathy; HC ⫽ hypertrophic cardiomyopathy; LVH ⫽ left ventricular hypertrophy; LVNC ⫽ left ventricular non-compaction cardiomyopathy; SD ⫽ sudden death.

were read 28.6 days after the venue, and the study results were mailed to the participants 89.5 days after the venue. In model 2, 3 events occurred, averaging 161.3 students/venue. In this latter model, the screening results were provided immediately to the participant. A total of 2,506 students were enrolled, with 2,022 screened according to model 1 and 484 according to model 2 (Figure 2). The average age was 14.5 ⫾ 1.77 years, 1,300 subjects were boys (52%), and the mean body surface area was 1.73 m2.

Most students were white (65.6%), followed by Hispanics and blacks. A total of 550 subjects (21.9%) reported ⱖ1 cardiovascular symptom with exercise, with 178 (32.4%) of 550 reporting ⬎1 symptom. Most (78%) reported no concerning cardiovascular family history. Approximately 14% reported a family history of either an “abnormal heart rhythm” or an “enlarged/thickened heart.” Of note, 33 students specifically mentioned a potentially hereditable familial condition: HC

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in 15, Marfan syndrome in 9, LQT syndrome in 3, ventricular fibrillation in 3, and SD in 4. Of the 2,506 ECGs performed, 57 (2.3%) were screen positive: 33 showed LV hypertrophy, 14 a prolonged QT interval, 7 WPW pattern, and 3 abnormal Q waves and repolarization abnormalities, concerning for potential CA abnormalities (Figure 3). There was 100% agreement for electrocardiographic interpretation among the screening and reviewing electrophysiologists regarding the identification of a screen-positive ECG using the predetermined, written electrocardiographic criteria. Of those students with concern for HC from the screening ECG, 24 of 33 had normal screening echocardiograms. Of those remaining, 9 continued to have concern after the screening echocardiogram and were referred for additional follow-up. However, only 3 pursed the recommendation and were ultimately found to have a no definitive evidence of HC. Of those with a prolonged QT interval, 13 of 14 pursued additional follow-up and 4 were subsequently diagnosed by cardiologists not involved with the present study with LQT syndrome and a ␤-blocker medication was initiated. No genetic testing has been performed to confirm the diagnosis. Of the 7 subjects with WPW, 4 pursued follow-up and eventually underwent an ablation procedure, and 2 were lost to follow-up. The remaining patient with WPW was subsequently diagnosed with dilated cardiomyopathy as well and is currently in the care of a pediatric cardiologist. Finally, of the 3 students with electrocardiographic findings suspicious for having a CA abnormality, only 1 chose to pursue follow-up and was found to have normal coronary artery anatomy. Thus, from the ECG screen alone, 11 of 57 subjects (0.4% of the total population screened) were ultimately diagnosed with concern for disease after a comprehensive evaluation by a pediatric cardiologist. A total of 2,051 screening echocardiograms were performed (Figure 4), of which 14 (0.7% of the population screened) were initially considered screen positive. Of these, 10 had concern for HC, 2 for LV noncompaction (LVNC), 1 for dilated cardiomyopathy, and 1 for subaortic stenosis. Of these, 8 subjects (57%) pursued follow-up and the following pathologic entity was diagnosed: dilated cardiomyopathy in 1, LVNC in 1, and early HC in 2, both of whom are being followed up conservatively and have been restricted from athletics by the primary cardiologist. On blinded review for validation purposes, neither the 1 case of LVNC nor the 2 cases of early HC met the criteria for disease diagnosis by either the review facility or the outside independent institution and, therefore, were not considered true screen-positive studies. Of the 33 screen-positive subjects based on their ECG and/or echocardiogram, 25 (66.7%) pursued the recommended follow-up evaluation. The research team made multiple attempts (range 4 to 9 attempts/student) to ensure follow-up for the remaining 8 students with abnormal screening studies, by telephone and certified mail. Barriers to follow-up included (1) an inability to reach the family, (2) parental denial of the recommendations, and (3) a lack of medical insurance. A retrospective analysis was performed to determine the incremental benefit of each stage of the screening process in ultimately identifying those at potential risk of SD. If the preparticipation questionnaire was used as the only form of screening, 895 students (35.7%) would have been referred

Table 3 Budget for screening pilot study Variable

Cost

Infrastructure Office space Administrative staff Medical equipment Office equipment/ supplies Subtotal Professional services Data storage/ transfer Enhanced electronic medical record for echocardiograms with servers Research costs Database development Data analysis Study coordinator Subtotal Report development Total operational costs

$22,255.00 $192,571.00 $170,709.00 $45,059.00 $430,594.00 $95,932.00 $48,219.00 $88,000.00

$50,000.00 $13,400.00 $94,500.00 $157,900.00 46,123.00 $866,768.00

Model 1

Screening Event Costs

Model 2

$3,704.16 $160.71 $234.00 $139.08 $186.72 — $4,424.67 72 $61.45

Staffing Supplies Registration forms Echocardiography/electrocardiography machines Travel and other miscellaneous Venue rental Total event costs Average number of participants Screening cost/participant

$5,264.58 $177.86 $528.00 $148.16 $385.67 $243.00 $6,747.27 162 $41.65

for a more comprehensive evaluation for sports clearance by a cardiologist, although ultimately disease was found in 11 (1.23%). Of the 550 subjects who reported cardiovascular symptoms with exercise, 5 (0.9%) were identified in the present study with screen-positive results: 3 with WPW, 1 with LQT, and 1 with dilated cardiomyopathy. Of the 345 subjects who reported concern for a potential family history of a life-threatening disease, 2 additional students (0.6%) were ultimately diagnosed with LQT syndrome. With the addition of the screening ECG and the questionnaire, 4 additional subjects were identified: 3 with WPW and 1 with LQT. Finally, the addition of the screening echocardiogram to the process further identified 3 subjects with concern for cardiomyopathy (2 with early HC and 1 with LVNC). Of note, although the 3 subjects with myopathy have been treated and followed up by their primary cardiologists, these subjects were determined not to meet the criteria for diagnosis, on either the screening echocardiogram or the more comprehensive echocardiogram, by both the reviewing facility and the independent review institution. An itemized summary of project costs is listed in Table 3. On a global scale, the State of Texas spent $1 million dollars to screen 2,506 students. If one were to simply include the actual cost to perform a screening venue, excluding infrastructure/equipment, nonmedical professional services, and research-related costs, the cost for model 1 screening was $61.45/student and was $41.65/student for model 2. This cost analysis did not address the substantial additional cost per student referred for a more comprehensive evaluation.

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Discussion Although nationwide acknowledgment and agreement exists among experts regarding the importance of preventing SD in youths and adolescents, consensus is lacking regarding the methods to achieve this goal. A significant impediment is inadequate data regarding the feasibility and efficacy of a large-scale screening process. The present study is the first large, prospective and fully state-funded screening initiative to identifying the potential causes of young athlete SD. Others have reported single-institutional success in screening student athletes using a standard, uniform screening protocol.2,9 –12 In contrast, our study population encompassed the ethnic and geographic diversity reflective of the State of Texas. In addition, the pilot funds were awarded to a collaborative group of investigators. We were able to provide the operational infrastructure and technical expertise to reliably perform mass screening of student athletes. Our study was intentionally not powered to address the efficacy of this screening process, nor was it designed to compare the models of screening. We did confirm the observations of others regarding the limited value of a preparticipation questionnaire and physical examination as the sole elements of this screening process.10,13–15 Using the questionnaire alone, 36% of the students would have been referred to seek a comprehensive evaluation by a cardiologist before sports participation clearance, when disease was only diagnosed in 7 of these subjects. There has been an appeal to incorporate echocardiograms and ECGs into routine screening of young athletes. Several studies have reported that abnormal findings are frequently found on the ECG in patients with asymptomatic, but potential lethal, cardiovascular disease, including HC, ARVC, and primary electrical disease.16 –21 In our study, 2.3% of students had electrocardiographic findings concerning for underlying cardiovascular conditions that could predispose to SD. On more comprehensive evaluation, only 11 were found to have true, potential life-threatening disease, translating to a specificity of 98% and a false-positive rate of 2%. Although these rates paralleled the findings of others,9,22 debate continues regarding whether the ECG is effective in actually reducing the overall rates of SD in the United States, in which the incidence of SD is already very low.14,23 The inclusion of the ECG in the athletic screening process was credited with a nearly 90% reduction in the prevalence of SD in young athletes in Italy3,4,24; however, the reduction resulted in a prevalence similar to that already present in the United States. Supporting this notion, a recent study by Steinvil et al25 found that mandatory electrocardiographic screening did not have any apparent effect on reducing the overall incidence of SD in Israeli athletes. The limitations in each of these studies precluded a definitive conclusion regarding the utility of the ECG as an effective screening method for SD in this young population. Although the reported incidence of HC in the general adult population is 1:500, in our study, of the 33 ECGs that were interpreted as “concern for HC,” no student was subsequently found to have HC on the more comprehensive evaluation. Other studies have shown a similarly low rate of an echocardiographic diagnosis of HC.9,11,26 Perhaps this can be attributed to disease that has not yet been phenotypically expressed

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in this young cohort, compared to that of the adult, further re-enforcing the need to re-evaluate this patient population repeatedly during adolescence. This could have implications for the appropriate age of screening to potentially detect HC. An important consideration for any screening program is the ability to reliably identify disease. A significant limitation is the interobserver variability in diagnosing disease. In our study, the agreement among investigators was 100% with respect to electrocardiographic interpretation in the identification of screen-positive/negative electrocardiographic studies. With respect to the echocardiogram, the agreement was 79% among investigators regarding screen-positive/negative studies. Specifically, 3 students were identified by both screening and follow-up comprehensive, echocardiographic studies as having cardiomyopathy: 2 with concerns for early HC and 1 with LVNC. All 3 subjects had their echocardiograms blindly reviewed retrospectively by an echocardiography specialist at 2 independent facilities, neither of whom concurred with the initial diagnosis of cardiomyopathy in any one of these 3 students. Others have likewise reported the lack of consensus on disease diagnosis, even among experts.22,27–30 This finding highlights the need for a prospective, national study to better define the diagnostic standards to clarify the true prevalence of the disease. Another significant issue we identified was that of ensuring follow-up evaluations. In our study, a dedicated research nurse and/or study coordinator attempted to contact families both verbally and by certified mail. Despite these aggressive attempts to contact students with abnormal screening results, a significant percentage (33.3%) did not pursue the recommended follow-up evaluation. The identified obstacles included an inability to reach/contact the students using the demographic information provided, denial by the family that an issue needed to be addressed, and a lack of health insurance and access to medical care. The screening of large populations of students can potentially be very costly, especially considering the low prevalence of disease in this young population. Lacking knowledge of the disease prevalence and screening program efficacy, the costeffective analysis has a high degree of uncertainty. Acknowledging this limitation, on an operational level, our study demonstrated that screening was feasible using a combination of history/physical questionnaires, electrocardiography and limited 2-dimensional echocardiography at reasonable cost. The infrastructure expenses, cost of the follow-up evaluation for false-positive results, and the necessity to perform serial screening evaluations in this population must ultimately be included in any meaningful cost-analysis. The purpose of the present study was to determine the technical feasibility, and, as such, we did not power the study to address the issue of efficacy of the screening process in identifying disease. The present study was a nonrandomized, observational study and was not designed to compare the 2 models of screening. We also recognize that the cost-analysis presented was limited to a technical, operational analysis and could not address the cost-effectiveness of screening in terms of the potential lives saved. Finally, and noteworthy, is that CA anomalies were not screened for adequately within the confines of a limited 2-dimensional screening echocardiographic study, such as was adopted in the present study. Given that CA abnormalities are the second-leading cause of SD in young

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athletes in the United States,15 this represents a significant limitation of the screening process. Acknowledgment: We appreciate Janet Smith, BA, and Ellen Suen, MS, for their assistance with the database development and organization, and Joan Reisch, PhD, MS, for her assistance with the biostatistical analysis and database development. We also thank Ben Eidem, MD (Mayo Clinic, Rochester), for his willingness to independently review the study echocardiograms. 1. Maron BJ, Thompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, Dimeff R, Douglas PS, Glover DW, Hutter AM, Krauss MD, Maron MS, Mitten MJ, Roberts WO, Puffer JC; American Heart Association Council on Nutrition, Physical Activity, and Metabolism, Roberts WO, Puffer JC. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643–1655. 2. Marek J, Bufalino V, Davis J, Marek K, Gami A, Stephan W, Zimmerman F. Feasibility and findings of large-scale electrocardiographic screening in young adults: data from 32,561 subjects. Heart Rhythm 2011;8:1555–1559. 3. Corrado D, Biffi A, Basso C, Pelliccia A, Thiene G. 12-Lead ECG in the athlete: physiological versus pathological abnormalities. Br J Sports Med 2009;43:669 – 676. 4. Corrado D, Pelliccia A, Heidbuchel H, Sharma S, Link M, Basso C, Biffi A, Buja G, Delise P, Gussac I, Anastasakis A, Borjesson M, Bjørnstad HH, Carrè F, Deligiannis A, Dugmore D, Fagard R, Hoogsteen J, Mellwig KP, Panhuyzen-Goedkoop NP, Solberg E, Vanhees L, Drezner J, Estes NA, Iliceto S, Maron BJ, Peidro R, Schwartz PJ, Stein R, Thiene G, Zeppilli P, McKenna WJ; Section of Sports Cardiology, European Association of Cardiovascular Prevention and Rehabilitation. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243–259. 5. Corrado D, Pelliccia A, Bjørnstad HH, Vanhees L, Biffi A, Borjesson M, Panhuyzen-Goedkoop NP, Deligiannis A, Solberg E, Dugmore D, Mellwig KP, Assanelli D, Delise P, van-Burren F, Anastasakis A, Heidbuchel H, Hoffmann E, Fagard R, Priori SG, Basso C, Arbustini E, Blomstrom-Lundqvist C, McKenna WJ, Theine G; Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Eur Heart J 2005;26:516 –524. 6. Maron BJ, Mitchell JH. 26th Bethesda Conference: Recommendations for detecting eligibility for competition in athletes with cardiovascular abnormalities. J Am Coll Cardiol 1994;24:845– 899. 7. Pellicia A, Zipes DP, Maron BJ. Bethesda Conference #36 and the European Society of Cardiology consensus recommendations revisited. J Am Coll Cardiol 2008;52:1990 –1996. 8. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group, American Society of Echocardiography’s Guidelines and Standards Committee, European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440 –1463. 9. Fuller CM, McNultry CM, Spring DA, Arger KM, Bruce SS, Chryssos BE, Drummer EM, Kelley FP, Newmark MJ, Whipple GH. Prospective screening of 5,615 high school athletes for risk of sudden cardiac death. Med Sci Sports Exerc 1997;29:1131–1138.

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