Non-COVID-19 cardiovascular pathology from return-to-play screening in college athletes after COVID-19

WHAT IS ALREADY KNOWN ON THIS TOPIC

Preparticipation screening in competitive athletes using history and physical examination and/or ECG is used to identify conditions associated with sudden cardiac arrest or death; however, the utility of transthoracic echocardiogram (TTE) for cardiac screening in athletes remains uncertain.

Return-to-play cardiac screening after SARS-CoV-2 infection in college athletes provides an opportunity to examine incidental non-COVID-19 cardiovascular pathology and to evaluate the incremental value of a screening TTE.

WHAT THIS STUDY ADDS

In the absence of ECG abnormalities, the added value of TTE is limited to pathological aortic root dilatation in approximately 1 in 1000 athletes and minor structural findings in 1 in 160 athletes.

The proportion of incidental and false-positive findings on TTE screening is high, and coronary artery anatomy and ascending aorta size are inconsistently evaluated.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Given the resources needed to perform TTE, and the high proportion of incidental and false-positive findings, the added value of TTE to ECG screening in college athletes is limited.

Future study will benefit from more consistent evaluation of the coronary artery anatomy and ascending aorta dimensions.

Background

Early in the COVID-19 pandemic, concern for cardiac involvement after SARS-CoV-2 infection led to widespread return-to-play cardiac screening in competitive athletes, most commonly using serum troponin, 12-lead ECG and two-dimensional transthoracic echocardiogram (TTE).1 2 This screening was performed in addition to standard preseason preparticipation screening (PPS) using personal/family history and physical examination (H&P), with or without ECG, in an attempt to identify competitive athletes with conditions associated with increased risk of sudden cardiac death (SCD).3–7 While TTE is sometimes employed during PPS to identify structural pathology not detected by H&P and/or ECG, its role as an adjunct to H&P and ECG remains uncertain.8–16

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study was designed to determine the prevalence and clinical outcomes of SARS-CoV-2 cardiac involvement in competitive college athletes.17 18 However, the data obtained through return-to-play cardiac screening after SARS-CoV-2 infection also provide an opportunity to examine the detection of non-COVID-19 cardiovascular pathology and the diagnostic performance of TTE during PPS. The purpose of this study is to characterise non-COVID-19 cardiovascular pathology in college athletes undergoing return-to-play cardiac screening after SARS-CoV-2 infection and to examine the incremental value of TTE when added to ECG during PPS.

Methods

This was a secondary analysis of a nationwide prospective multicentre observational cohort study. College athletes included in this study had undergone return-to-play cardiac screening after a confirmed SARS-CoV-2 infection with both ECG and TTE. Athletes with a known cardiovascular diagnosis and those diagnosed with possible, probable or definite myocarditis and/or pericarditis on cardiac MRI were excluded. Study enrolment procedures and definitions have been previously described.17

Data collection was performed between September 2020 and June 2021. Participating institutions submitted de-identifed data via a standardised data capture tool, which captured demographic information and cardiovascular testing results. Copies of de-identified ECGs and clinical reports of other testing were also requested for each athlete. Each institution maintained a link to patient identifiers which was not provided nor accessible to the study investigators.

Abnormal ECG and/or TTE findings were characterised by severity, as adjudicated by an investigator panel of cardiologists and sports medicine physicians with expertise in sudden cardiac arrest (SCA) or death in athletes: ‘major’—clinically actionable disorders associated with an increased risk of SCA/SCD, or requiring intervention19; ‘minor’—not associated with SCA/SCD but warranting continued surveillance; ‘incidental’—not associated with SCA/SCD and not warranting surveillance or ‘uncertain significance’—abnormal TTE report with subsequent normal follow-up testing, suggesting a false-positive initial interpretation or transient abnormality (figure 1). Standard descriptive statistics were used to describe the study population; continuous variables were summarised via means and SD and categorical variables were described with frequencies and percentages. The prevalence estimates for cardiovascular pathology findings are reported as percentages using the total number of athletes identified with the condition, divided by the study population.

Figure 1Figure 1Figure 1

Classification of echocardiographic findings by severity. SCA/D, sudden cardiac arrest or death; TTE, transthoracic echocardiogram.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

ResultsStudy population

Forty-five participating institutions submitted data regarding 3685 athletes to the ORCCA registry during the study period, including 3004 athletes who had undergone both ECG and TTE screening. One-hundred four athletes (3%) were excluded from this analysis: 30 with pre-existing cardiovascular diagnoses, and 74 with possible, probable or definitive myocardial and/or pericardial SARS-CoV2 involvement (figure 2). Table 1 provides baseline demographic characteristics of the final cohort, comprising 2900 athletes (mean age 20±1, 32% female, 64% white, 27% black). Athletes participated in 26 different sports. The most commonly represented sports were football (n=1010, 34.8%), baseball (n=272, 9.4%) and track and field (n=218, 7.5%).

Figure 2Figure 2Figure 2

Study design and selection of athlete cohort. ORCCA, Outcomes Registry for Cardiac Conditions in Athletes; TTE, transthoracic echocardiogram.

Structural and non-structural cardiovascular findings

Structural and non-structural findings are summarised in figure 3. Thirty-five (1.2%) athletes had an abnormal ECG. Three athletes had major findings: paroxysmal atrial fibrillation requiring cardioversion (n=1); apical-variant hypertrophic cardiomyopathy (n=1) and suspected cardiomyopathy characterised by left ventricular dilation and non-compaction (n=1). The remaining 32 athletes with an abnormal ECG had no structural or functional findings on TTE, thus representing a false-positive ECG result (1.1%).

Figure 3Figure 3Figure 3

Summary of structural and non-structural findings in patients undergoing ECG and TTE screening. ASA, atrial septal aneurysm; ASD, atrial septal defect; BAV, bicuspid aortic valve; DCM, dilated cardiomyopathy; GLS, global longitudinal strain; HCM, hypertrophic cardiomyopathy; LV, left ventricle; LVH, left ventricular hypertrophy; LVNC, left ventricular non-compaction; MV, mitral valve; MVP, mitral valve prolapse; PFO, patent foramen ovale; RV, right ventricle; TTE, transthoracic echocardiogram; WMA, wall motion abnormalities. *Some athletes had more than one minor or incidental finding.

Among athletes with a normal ECG, major/clinically actionable findings were confined to three individuals with aortic root dilatation ≥40 mm (table 2). Fifteen (0.5%) athletes exhibited minor cardiovascular findings, most commonly bicuspid aortic valve without haemodynamically significant regurgitation or stenosis and borderline aortic enlargement <40 mm (table 3). Twenty-five (0.8%) athletes had incidental findings including patent foramen ovale (PFO), PFO versus atrial septal defect (ASD) and reduced global longitudinal strain (table 4). Eleven (0.4%) athletes had findings of uncertain significance, with abnormal initial findings on TTE and normal follow-up testing suggesting an initial false-positive finding or the presence of transient abnormalities (table 5).

Table 2

Clinical characteristics for athletes with major cardiovascular diagnoses

Table 3

Clinical characteristics for athletes with minor cardiovascular diagnoses

Table 4

Clinical characteristics for athletes with incidental cardiovascular diagnoses

Table 5

Clinical characteristics for athletes with findings of uncertain significance

Additional cardiovascular testing and follow-up

Twenty-four athletes received additional cardiovascular testing following screening ECG and TTE, including 23 with abnormal TTE findings (online supplemental table S1). Cardiovascular magnetic resonance (CMR) was performed in 21 athletes, and stress testing (including cardiopulmonary exercise testing and stress echocardiography) and outpatient cardiac event monitoring were conducted in three athletes each. In nine athletes, follow-up testing confirmed TTE findings. CT angiography found one new incidental diagnosis of a bovine aortic arch. The remainder of follow-up testing did not reveal any significant structural or electrical pathology.

Two athletes were restricted from competition. One athlete with dilated cardiomyopathy and suspected left ventricular non-compaction was restricted with results of genetic testing for cardiomyopathy pending at time of data acquisition. Another athlete with mild left ventricular dilation and an ejection fraction of 47% was restricted, with CMR results interpreted as non-ischaemic cardiomyopathy versus normal physiological adaptation; these findings were subsequently classified as being of uncertain significance.

Among other athletes diagnosed with major cardiovascular diagnoses, the athlete with HCM returned to play and one athlete underwent cardioversion for paroxysmal atrial fibrillation. No restrictions were placed on athletes with aortic root dilatation and no other cardiovascular interventions were conducted during the study period.

Discussion

In a cohort of 2900 college athletes without known cardiovascular pathology who underwent ECG and TTE screening for return to play, 57 (2.0%) had electrocardiographic or echocardiographic abnormalities, including 5 (0.2%) with major structural abnormalities associated with an elevated risk of SCA/SCD and 15 (0.5%) with conditions warranting further surveillance. Of 54 athletes with normal ECG, the added value of TTE was limited to the identification of presumably pathological but mild aortic root dilatation in three (0.1%) athletes.

The low prevalence of structural pathology in this cohort is consistent with prior studies using preparticipation echocardiography at American universities. Screening TTE in 964 athletes at the University of Kansas found only 8 (0.8%) with major structural abnormalities11; a pilot study of a limited ‘5 min’ TTE at the University of Wisconsin noted minor abnormalities in 5 of 395 (1.3%) athletes screened,16 and a later retrospective study there reported 49 of 2898 (1.7%) athletes undergoing TTE had findings requiring follow-up and 3 (0.1%) had major findings meriting exclusion from competition.13 Similar echocardiographic findings are also present in large cohorts of preadolescent and adolescent soccer players in the USA and Europe (1.8%–4.5% minor findings, 0.1%–0.3% major findings),8 9 12 15 as well as professional athletes in Spain and Italy (0.4%–5.7% minor findings, 0.2–0.3% major findings).10 14

A key consideration to using TTE in during PPS among competitive athletes is its incremental value above the standard of H&P and/or ECG, which are relatively inexpensive and readily available compared with echocardiography.20 21 In prior studies employing a preparticipation TTE, 15 of the 38 (39.5%) athletes excluded from competition had antecedent H&P or ECG findings.8–16 Additionally, a prospective study of young competitive athletes with SCA/SCD by Peterson et al reported that 71% of aetiologies were potentially detectable on ECG, whereas approximately 20% (coronary artery anomalies, aortopathies, valvular disorders and congenital heart defects) would likely show TTE abnormalities in the setting of a normal ECG.22

Our findings suggest the added value of TTE to preparticipation ECG is low, particularly for the detection of cardiomyopathies. Both athletes in this cohort diagnosed with cardiomyopathies had an abnormal ECG. In athletes with a normal ECG, the added value of TTE was limited to pathological aortic root dilatation in 0.1% and minor structural abnormalities in 0.5% of athletes. While aortic dilatation has been associated with an elevated risk of SCD via aortic rupture or dissection,12 20 21 23 outcomes data among athletes with aortic dilatation in the absence of an underlying genetic or hereditary aortopathy are limited. One small longitudinal study of athletes with isolated aortic dilatation suggests that clinically significant complications may be rare.24–26 Indeed, aortic rupture and dissection represent only a small proportion (3%–5%) of SCD cases in US athletes.19 22 Notably, all athletes with an enlarged aorta in our cohort continued sports participation after testing.

Importantly, the rate of incidental TTE findings and findings of uncertain significance in this cohort was high: 36 of 54 (67%) athletes with an abnormal TTE but normal ECG had clinically insignificant findings or normal follow-up testing, yielding a positive predictive value of only 35.7% for structural findings warranting surveillance. Additional testing prompted by TTE findings was also of limited diagnostic benefit: only 1 of 23 athletes who underwent follow-up testing had findings not already suggested by TTE.

Study limitations

A key limitation of this study was the inconsistent evaluation of coronary artery anatomy and ascending aorta size. As previously reported, only 10 of 56 (18%) echocardiography laboratories used by the 45 institutions providing data to the ORCCA study regularly commented on coronary anatomy,27 and although aortic root size was commonly reported, only 15 of 45 institutions consistently measured ascending aorta size. As a result, it is possible that structural abnormalities in this cohort were missed and the incremental value of a screening TTE is actually higher than reported in this cohort. Anomalous origin of a coronary artery is among the top three reported causes of SCD in athletes, comprising up to 17% of cases, and is the most common cause of SCD/SCA not typically detectable on ECG.21 28 29 Large cohorts have demonstrated that coronary artery origins are detectable in 96%–99% of cases using TTE,13–16 and American College of Cardiology/American Heart Association guidelines state that any echocardiographic evaluation of athletes should attempt to characterise coronary anatomy.30 Thus, inconsistent coronary evaluation represents a notable limitation in this study and gap in current TTE interpretation protocols.

Other limitations in this study include the reliance on imaging reports, rather than investigator review and adjudication of original images, for interpretation of TTE and CMR results. As such, inter-reader reliability of echocardiographic interpretation could not be performed. Similarly, all screening and diagnostic testing was performed and interpreted by the institutions submitting data to the ORCCA study, and the lack of a standardised interpretation and reporting protocol across all institutions could have impacted results. Additionally, the proportion of athletes in our cohort who had previously undergone PPS, and the results of that screening, were unknown. This may have impacted pathological findings in our athlete cohort, similar to Italian studies that found lower rates of echocardiographic findings in athletes who had previously undergone PPS.14 15 Likewise, the population of athletes who participated in this registry, although large, may not be fully representative of a non-selected population of athletes. Finally, all diagnostic testing performed in this cohort occurred during return-to-play screening after SARS-CoV-2 infection, and therefore may not represent standard PPS protocols or timing.

Conclusions

Return-to-play cardiac screening after SARS-CoV-2 infection revealed major non-COVID-19 cardiac pathology in approximately 1 in 500 athletes. In the absence of ECG changes, however, the added value of TTE was limited to pathological aortic root dilatation in approximately 1 in 1000 athletes and minor structural findings warranting surveillance in 1 in 160 athletes. Two-thirds of TTE abnormalities had no clinical significance. Given the resources needed to perform TTE, and the high proportion of incidental and false-positive findings in this cohort, the incremental value of TTE as currently practised remains small. Further study, including standardised aorta and coronary artery evaluation, is necessary to better inform the potential role of screening TTE.

Data availability statement

Data are available on reasonable request. ORCCA data are available on reasonable request.

Ethics statementsPatient consent for publicationEthics approval

This study was approved by Massachusetts General Brigham Institutional Review Board (protocol #2020P002667). Participating institutions provided de-identified data to the ORCCA study, and each institution maintained their own link to patient identifiers which was not provided nor accessible to the study investigators. Individual consent was not required nor provided consistent with our approved Human Subjects protocol.

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