Prevention of sudden death in adolescent athletes: Incremental diagnostic value and cost-effectiveness of diagnostic tests

Abstract

Introduction

Pre-participation screening in athletes attempts to reduce the incidence of sudden death during sports by identifying susceptible individuals. The objective of this study was to evaluate the diagnostic capacity of the different pre-participation screening points in adolescent athletes and the cost effectiveness of the programme.

Methods

Athletes were studied between 12–18 years old. Pre-participation screening included the American Heart Association questionnaire, electrocardiogram, echocardiogram, and stress test. The cost of test was established by the Catalan public health system.

Results

Of 1650 athletes included, 57% were men and mean age was 15.09 ± 1.82 years. Positive findings were identified as follows: in American Heart Association questionnaire 5.09% of subjects, in electrocardiogram 3.78%, in echocardiogram 4.96%, and in exercise test 1.75%. Six athletes (0.36%) were disqualified from participation and 10 (0.60%) were referred for interventional treatment. Diagnostic capacity was assessed by the area under the curve for detection of diseases that motivated disqualification for sport practice (American Heart Association questionnaire, 0.55; electrocardiogram, 0.72; echocardiogram, 0.88; stress test, 0.57). The cost for each athlete disqualified from the sport for a disease causing sudden death was €45,578.

Conclusion

The electrocardiogram and echocardiogram were the most useful studies to detect athletes susceptible to sudden death, and the stress test best diagnosed arrhythmias with specific treatment. In our country, pre-participatory screening was cost effective to detect athletes who might experience sudden death in sports.

Introduction

The incidence of sudden cardiac death (SCD) among young athletes is estimated at two per 100,000 athletes per year;¹ however, its impact has devastating consequences for the athlete’s family and society. A single cohort study has shown that pre-participation screening (PPS) to identify individuals susceptible to sudden death during sports is a useful prevention strategy.²

The inclusion of the electrocardiogram (ECG) in the PPS is currently a controversial issue; while the European Society of Cardiology suggests incorporation,^3,4 the American Heart Association considers personal and family history, and physical examination as the only PPS evidence needed.⁵ In turn, although the addition of echocardiography was suggested 20 years ago⁶ and has proven its usefulness,^7–10 cost has limited its routine implementation.¹¹ Scientific evidence also suggests that the addition of stress test could be useful in those older than 30 years.¹² Although several studies have assessed the cost effectiveness of adding the ECG to PPS;^13–19 a decision-model analysis¹¹ and a recent meta-analysis²⁰ have not provided conclusive information.

In this context, the aim of our study was to evaluate the different elements of PPS in a cohort of adolescent competitive athletes, following the Consensus of Catalonia recommendations²¹ and analyse the cost effectiveness of each of the four items used in the PPS in our population.

Methods

Design

Athletes between 12–18 years old participating in various sports were enrolled consecutively from January 2012–December 2015. All of them were part of a highly competitive sports programme of the Consell Català de l'Esport or the Futbol Club Barcelona.

The study follows the guidelines for reporting observational studies in accordance with standards established by the Declaration of Helsinki and received the approval of our centre’s Ethics Committee for Clinical Research. Written consent was obtained from individuals older than 16 years of age and from a parent for younger athletes.

Examination protocol

In all athletes, cardiovascular evaluation consists of four points: (a) family-personal history and physical examination was interrogated using the American Heart Association (AHA) 12-point questionnaire²² which was given to each subject to be filled in and then reviewed together with the patient by the attending cardiologist; (b) ECG analysed according to the Seattle criteria;²³ (c) Doppler echocardiography screening protocol in athletes,⁹ not interpreting slight mitral and tricuspid insufficiencies as pathological if valves are structurally normal;¹⁰ and (d) maximal stress test, a treadmill protocol was used, starting at 6 km/h with progressive speed increases of 1 km/h every minute and a fixed slope of 1% until maximum effort was reached.²⁴

The 12-lead ECG was performed in the supine position at a speed of 25 mm/s and with amplitude of 10 mV. Doppler echocardiography was done with standard equipment (Vingmed Vivid-7, General Electric Vingmed, Milwaukee, Wisconsin, USA, or Aplio 400, Toshiba Medical Systems Corporation, Otawara, Japan). The stress test was performed on a treadmill with digital equipment that allowed off-line analysis of ECG tracing (CASE Exercise Testing System, GE Medical Systems, Milwaukee, Wisconsin, USA; or Medisoft, Sorinnes, Belgium). All studies were conducted by sports physicians and cardiologists, recorded in digital form for further analysis and reviewed by the whole team if there was any controversy.

European recommendations were followed for the treatment of pathologies identified and the disqualification of athletes from participation in the case of cardiomyopathies and valvular disease,²⁵ arrhythmias and channelopathies,^26,27 and congenital heart disease.²⁸ Following these recommendations, four groups were established: (a) athletes with normal tests; (b) athletes with indications for annual monitoring; (c) athletes to be subjected to specific treatment before continuing competitive sport training; and (d) athletes disqualified from competitive sport.²⁹

Cost

The cost calculation of each item in the protocol was based on Health Institute of Catalonia data published in the Diari Oficial de la Generalitat de Catalunya,³⁰ as follows: medical visit AHA questionnaire (family-personal history and physical examination), €40; ECG, €18; Doppler echocardiography, €56; stress test, €31. The total cost of the PPS was €145 per athlete. The total cost for second-line studies was €3454; electrophysiology, €2800; cardiac magnetic resonance, €276; coronary tomography, €197; and 24-hour Holter ECG, €36. Cost-effectiveness was calculated by determining the cost for each athlete disqualified from sports participation, as a strategy for prevention of sudden death in athletes. The official exchange rate used was €1.00 = US$1.10.

Statistical analysis

In the descriptive analysis, quantitative variables were expressed as mean ± standard deviation. Discrete variables are presented as number of cases and percentages. Sensitivity and specificity were calculated using standard procedures. Diagnostic capacity was assessed by positive (sensitivity/1-specificity) and negative (1-sensitivity/specificity) likelihood ratios, and pathologies that required treatment or disqualification of sport were determined by the area under the curve. All data were analysed using the SPSS statistical package (version 19, SPSS Inc., Chicago, New York, USA).

Results

A total of 1650 athletes were evaluated, with a mean age of 15.09 ± 1.82 years (59.8% men). All athletes were Caucasian, with a weekly average of 13.42 ± 4.07 training hours in different sports disciplines and at different levels of competition (Table 1).

Table 2 details each of the diagnostic points of the PPS. Positive findings were found for the 12-point AHA questionnaire in 84 (5.09%) athletes, ECG in 65 (3.93%), Doppler echocardiography in 79 (4.78%) and stress test in 29 (1.75%).

The population was divided into four groups after the PPS: (a) normal studies, n = 1462 (88.60%); (b) minor alterations that require annual monitoring (10.48%); (c) athletes requiring a specific treatment in order to continue competing in sports, n = 10 (0.60%); and (d) athletes disqualified from participation in sports, n = 6 (0.36%) for the following diseases: hypertrophic cardiomyopathy (three), anomalous origin of coronary artery (one), pectus excavatum (one), and compression of the right ventricle (one) (Figure 1). The treatments required to continue competing included two closures of inter-atrial communications and eight radiofrequency ablations, for supra-ventricular paroxysmal tachycardia, frequent premature ventricular complex (PVC), atrial fibrillation, and the remaining five for ventricular pre-excitation.

Table 3 shows the capacity of each of the screening tools to detect a need for a specific treatment or disqualification from sport participation. The ECG and echocardiogram had the better diagnostic capacity to detect athletes who should be disqualified, while ECG, Doppler echocardiography and stress testing were most useful for identifying those requiring specific treatment. The AHA questionnaire lacked adequate diagnostic capability due to the low sensitivity values and a positive and negative likelihood ratio near one.²⁰ The cumulative diagnostic yield of the tests used in the PPS was analysed in Figure 2.

Table 4 shows the total cost of the PPS and the frequency with which an additional study or specific treatment was indicated, with the cost of each shown in euros. The program cost divided by each of the six disqualified athletes was €45,578 (US$50,135).

Discussion

This study analysed PPS in competitive adolescent athletes included in a high-performance sports programme, showing that the ECG is a useful cardiological assessment. The addition of Doppler echocardiography was useful for detecting diseases that require disqualification from competitive sport, and the stress test was useful for pathologies that require specific treatment. The program for prevention of sudden death in sport (ECG, Doppler echocardiography and stress test) was cost-effective in our environment by identifying diseases that can cause sudden death in athletes or their immediate families.

AHA questionnaire

The 12-point AHA questionnaire²² has been accepted for international use, and since 2014 has added two points compared to the previous disqualification and heart disease genetic basis relatives.³¹ In our study, positive identification by the AHA questionnaire had limited usefulness.²⁰ However, given its low cost and that it is the gateway to the PPS, the AHA questionnaire can be considered essential in the screening program, but should not be used in isolation. One limitation we have observed in our experience but not found previously discussed elsewhere is the lack of rigour with which these questionnaires can be completed by athletes, to the extent of omitting some or all data in reporting.

ECG

Surprisingly, there is still controversy about the usefulness of ECG in the USA⁵ due to its cost-effectiveness³¹ and the percentage of false positives under European Society of Cardiology criteria,³² which exceeded 10%.³³ In 2013, the Seattle criteria²³ were published, which decreased the percentage of false positives to less than 5%.^33,34 Therefore, we used the Seattle criteria and retrospectively reanalysed the ECGs performed prior to that publication. We did not apply the redefined criteria,³⁵ because, although they have been shown to improve diagnostic specificity in black subjects, no additional diagnostic value has been demonstrated in Caucasian individuals. The alterations that motivated the taking of behaviour in athletes were three: (a) presence of negative T waves, (b) pre-excitation, and (c) PVCs. In our study, a positive ECG increased the probability of identifying diseases requiring specific treatment, as well as disqualifying young people from sports, so we consider the ECG indispensable in a PPS.

Doppler echocardiography

Since 1995, echocardiography has been increasingly incorporated into PPS⁶ because it provides added diagnostic value to physical examination and ECG in three main pathologies:¹⁰ (a) hypertrophic cardiomyopathy with normal ECG, (b) anomalous origin of coronary arteries, and (c) diseases of the aorta. Some groups have suggested using a five-minute directed ECG;⁷ in our case, we carried out a full protocol to assess the size and function of the heart chambers, valves and aorta as well as the origin of the coronary arteries.⁹ In our environment, it is also recommended that all high-performance athletes undergo a Doppler echocardiogram and a stress test during PPS.²¹

The incidence of abnormalities detected by echocardiography was less than 5%; this is consistent with the literature^8–10,36 and generated eight (0.04%) cardiac resonance tests to complete the diagnosis at a reasonable additional expense within the total cost of the PPS.

Stress test

The scientific evidence on the usefulness of the stress test in PPS is scarce, and is based on a study of a large cohort¹² that showed detection of ventricular arrhythmia to be a marker for heart disease that led to behavioural changes in athletes. Another recent study shows that the presence of more than 10 diagnoses of premature ventricular complex during the test would be significantly related to the presence of pathology.³⁷ The stress test in our study showed a good diagnostic ability to detect pathologies that require specific treatment, especially possible arrhythmias to treat with radiofrequency ablation. We believe there are three situations in which adding a stress test to PPS is beneficial in this age group: (a) ventricular arrhythmia occurs when maximum effort is sustained during exercise, (b) supra-ventricular arrhythmia occurs during exercise, and (c) ST segment depression occurs in athletes.

Cost-effectiveness

According to the data from our study and in the literature, an analysis of 100,000 PPS will disqualify about 300 athletes;^19,38–40 however, the annual incidence of sudden death in sports is two in 100,000 athletes.¹ We acknowledge the limited value of our cost-effectiveness study in the sense that the correct calculation for cost effectiveness should be that including the prevention of sudden cardiac death in the athletes and their families throughout their lives. Further long term follow-up registries might be of help in the future.

The scientific evidence regarding the use of PPS to reduce sudden death events in athletes is both complex and scarce. Results from a single cohort with follow-up have been published in relation to this topic.² Therefore, we consider it appropriate to include the deaths of athletes at rest, athletes revived by cardiopulmonary resuscitation, and the potential for prevention in first degree relatives (Figure 2) in the analysis.

In our environment, the PPS cost for each athlete was estimated at €145 (US$159.50); adding the total cost of the 2nd line of studies, the cost for each disqualified athlete was €45,578 (US$50,135). The classical measure of efficiency has drawn the line at US$50,000 per year of life gained;^11,41 however, the World Health Organisation suggests that interventions that fall between up to three times the gross domestic product per capita should be considered cost-effective.⁴⁴ Bearing in mind that the gross domestic product per capita in Catalonia in 2015 was €28,997,⁴⁵ in our country the PPS is a cost-effective measure to reduce the incidence of sudden death.

In summary, the European Society of Cardiology suggests PPS consisting of family and personal history and ECG;³ in competitive athletes, Doppler echocardiography can be added, as suggested in our country’s guidelines.²¹ This PPS intervention was cost effective.

Limitations

The study had three main limitations: (a) all athletes were competitive and were included in a programme of high performance training, which could generate a potential selection bias; therefore, translation of the current results to recreational athletes must be taken with caution; (b) In rare diseases such as long QT, arrhythmogenic cardiomyopathy or some other congenital syndromes, the expected costs could have been even higher due to the use of genetic testing. However, these are on the one hand infrequent cases, and on the other, genetic testing is becoming more and more available and less expensive due to the use of multiple diagnosis kits and advanced molecular biology techniques; (c) considering that the athletes usually start their competitive training program at age 12 years; we can consider that the studied population had an average of three years of training; this time may be too short to induce significant cardiac remodelling or even pathological abnormalities that could be detected in the pre-participation screening tests evaluated in the study; and (d) the cost of diagnostic studies in our country is lower than that reported in other countries.^11,18,41 The latter is a key point for cost-effectiveness, and in turn limits extrapolation of these data to other countries.

Conclusion

The ECG and echocardiogram were the most useful screening tools for detecting athletes susceptible to sudden cardiac death. The stress test was most useful for diagnosing arrhythmias requiring specific treatment. The 12-point AHA questionnaire had weak diagnostic utility. In our setting, the PPS was cost-effective to detect athletes susceptible to sudden death in sport.

Author contribution

All authors have contributed to the conception and design of the work. All authors contributed to the acquisition; GG, MSG, BV, GSB, JB and MS contributed to the analysis; GG and MS contributed to the interpretation of data for the work. GG, MSG and MS drafted the manuscript. All authors critically revised the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was partly funded by an unconditional grant from the Memora Group and by the National R & D Plan of Spain’s Ministry of Science and Innovation 2011-2013 (DEP 2010-20565) and Ministry of Economy and Competitiveness 2013 (DEP2013-44923-P), and the Generalitat de Catalunya (FI-AGAUR 2014-2017, RH 040 991).

References