Post-viral myocarditis is a well-documented cause of sudden cardiac death in athletes.^1,2 Myocarditis is often suspected but rarely confirmed by endomyocardial biopsy (EMB), which has created a need for noninvasive diagnostic criteria to guide recommendations for athletic participation and return to play (RTP) protocols.

Acute myocarditis is diagnosed by the presence of both a clinical syndrome, that includes acute heart failure, angina-type chest pain, or myopericarditis of <3 months duration, and an otherwise unexplained elevation in serum troponin, electrocardiographic features of cardiac ischemia, high-degree AV block or arrhythmias, and/or wall motion abnormalities with or without pericardial effusion on echocardiography or cardiac MRI (CMR).³ The 2018 Lake Louise Criteria expanded the diagnostic role of CMR, noting alterations in tissue signal on T2- or T1-weighted images and presence of late gadolinium enhancement (LGE) could indicate myocarditis in symptomatic individuals.⁴

During the 2019 novel coronavirus (COVID-19) pandemic, data showing myocardial involvement in infected individuals, as well as popular news stories of high-profile athletes being sidelined by presumptive COVID-19-related myocarditis, raised concerns about the safety of allowing athletes to RTP after COVID-19 infection.^5,6 Experts currently recommend a symptom-based return to exercise and imaging for those with moderate to severe symptoms, especially cardiopulmonary symptoms (Figure 1).⁷

Figure 1: RTP Guidelines in COVID-19-Positive Athletes. Courtesy of Gagel AC, Sharma G, Blumenthal RS, Martinez MW. Adapted from Phelan D, Kim JH, Chung EH. A game plan for the resumption of sport and exercise after Coronavirus disease 2019 (COVID-19) infection. JAMA Cardiol 2020;5:1085-86.

CMR in COVID-19 Positive Athletes - The Data Thus Far
Multiple studies of cardiac outcomes in athletes previously infected with SARS-Co-V2 have been conducted since September 2020 (Table 1) and have shown variable prevalence estimates of cardiac involvement ranging from 0-15%. Most studies included a CMR-based screening approach utilizing the Lake Louise Criteria in aiding diagnosis. Two studies noted positive CMR findings by Lake Louise Criteria in asymptomatic athletes with previous negative cardiac testing. A single study revealed a high prevalence of pericardial involvement, which is discordant from findings reported in other studies. Reassuringly, no deaths were attributed to COVID-19-related myocarditis in these studies.

Table 1: Studies in COVID-19-Positive Athletes, Summary of Key Findings. Courtesy of Gagel AC, Sharma G, Blumenthal RS, Martinez MW.

Study	Participants	Athletes	Findings
Rajpal et al.8	26	Collegiate	All had normal TnI level and no ECG or TTE findings; 15% had CMR findings suggestive of myocarditis (T2 signal an LGE); 2 athletes with +CMR were asymptomatic.
Vago et al.9	12	Professional	All had normal TnI levels and no cardiac symptoms; CMR showed no myocardial or pericardial edema or LGE.
Clark et al.10	59	Collegiate	All had normal ECG, TnI, and TTE; 3% met criteria for myocarditis.
Malek et al.11	26	Professional	15% had detectable Tn-I. CMR abnormalities found in 5 (19%) athletes, 4 with isolated myocardial edema and 1 with LGE with pleural and pericardial effusion. CMR did not reveal any case of acute myocarditis.
Starekova et al.12	145	Collegiate	2 (1.4%) had cardiac MRI findings consistent with myocarditis. 81.4% were symptomatic with 4.8% experiencing chest pain.
Brito et al.13	54	Collegiate	1 had elevated Tn-I levels. 46 of 54 underwent CMR. 27 of 46 (56.3%) had abnormal CMR findings. 19 (39.5%) had pericardial late enhancements with associated pericardial effusion. Native T2 findings were normal in all; no specific imaging features of myocardial inflammation identified.
Martinez et al.14	789	Professional	Abnormal screening identified in 30 (3.8%; tn-I, 6 [0.8%]; ECG, 10 [1.3%]; TTE, 20 [2.5%]). 27 had CMR; 5 (0.6%) had imaging evidence of inflammatory heart disease.
Moulson et al.15	3,018	Collegiate	13% had cardiopulmonary symptoms. 21/2999 had abnormal (0.7%), 24/2719 had elevated Tn-I (0.9%), and 24/2556 had abnormal TTE (0.9%). 198 athletes had CMR. 3/198 (1.5%) had definite or probable cardiac involvement.
Hendrickson et al.16	137	Collegiate	Tn-I levels abnormal in 4 (2.9%). There were no ECG or TTE abnormalities; 5 underwent CMR. None had abnormal findings detected by CMR.
Daniels et al.17	1,597	Collegiate	CMR done in all COVID-19-positive athletes regardless of cardiac symptoms or other cardiac testing results, increasing the prevalence of detecting myocarditis to 2.3%.
CMR: Cardiac MRI, TnI: Troponin-I, TTE: Transthoracic Echocardiogram, LGE: Late Gadolinium Enhancement, ECG: Electrocardiogram

Challenges in Differentiating the Athlete's Heart from Possible COVID-19 Cardiac Injury
"Abnormal" findings concerning for myocarditis can be normal variants in athletes, and several clinical challenges may arise in differentiating normal exercise-induced cardiac changes from pathologic insults as a consequence of COVID-19 infection. In healthy individuals, exercise can lead to transient elevations in troponin and short-term myocardial inflammation and tissue edema by CMR. Echocardiographic studies in endurance athletes have shown left ventricle (LV) dilation, reduced left ventricular ejection fraction (LVEF), and right ventricular remodeling, and several studies have suggested increased prevalence of fibrosis in endurance athletes above 30 years of age (with no increased association of arrhythmia).^18-24 Furthermore, in a CMR study from Clark et al., when COVID-19-positive athletes were compared to retrospective controls, focal LGE at the right ventricle insertion was present in 22% of study subjects compared to an identical LGE pattern in 24% of athletic controls.¹⁰ Thus, with current data, it remains difficult to determine if abnormal diagnostic, echocardiographic, and CMR findings in COVID-19 positive athletes are truly abnormal and concerning versus normal variants of the athletic heart.

Appropriate Screening in COVID-19-Positive Athletes
Potential cardiac injury in COVID-19 patients is concerning and warrants diagnostic investigation. Symptomatic individuals diagnosed with myocarditis of any etiology have higher rates of all-cause mortality independent of clinical symptoms, though it is unclear whether these rates extend to athletes with asymptomatic or mildly symptomatic disease.²⁵

Daniels et al. reported CMR in all athletes testing positive for COVID-19 by polymerase chain reaction, regardless of symptoms, yielded a 7.4-fold increase in diagnosing myocarditis compared to a symptom-driven strategy and a 2.8-fold increase compared to standard triad testing (ECG, echocardiogram, troponin).¹⁷ However, Moulson et al. noted the diagnostic yield of CMR was 4.2 times higher for a clinically indicated CMR versus a screening CMR.¹⁵ Of note, the Lake Louise Criteria were developed for patients with a clinical presentation consistent with myocarditis, not asymptomatic individuals. The specificity of current CMR myocarditis criteria in an asymptomatic and otherwise healthy population is unknown and cannot be confidently applied to athletes with low clinical test probability for myocarditis.²⁶

Studies to date support current recommendations that asymptomatic or mildly symptomatic athletes fully recovered from SARS-CoV-2 infection without cardio-pulmonary symptoms may return to sport without cardiac testing. Cardiac evaluation including ECG, troponin, and transthoracic echocardiography (TTE) should be considered in athletes with moderate-to-severe and/or cardiopulmonary symptoms during initial illness or upon return to exercise.⁷ CMR is most useful in athletes with high pretest probability for SARS-CoV-2 cardiac involvement based on the presence of cardiopulmonary symptoms and/or abnormalities on cardiac testing. Despite the use of CMR for the diagnosis of myocarditis, current RTP guidelines do not advocate using CMR when making RTP decisions (see Figure 1).⁷ Moreover, it is unresolved whether resolution of myocarditis related LGE should be required to permit return to competitive sports.⁴

Conclusion
As use of CMR increases in the evaluation of athletes convalesced from COVID-19, caution is required when determining the screening utility of CMR in the absence of diagnostic specificity. It also remains unclear whether isolated cardiac abnormalities detected by CMR harbor a risk like clinically diagnosed myocarditis.

CMR is an expensive resource requiring a level of expertise for interpretation not widely available. Incorporating a universal CMR screening approach in COVID-19-positive athletes would place stress on healthcare resources with likely little clinical benefit. Lessons learned from the introduction of ECG screening for athletes show that, in the absence of standardized measurements and normative data, use of CMR may result in inordinate false-positive rates, leading to unnecessary downstream testing and unwarranted medical disqualifications.²⁷ Future recommendations are expected to provide improved guidance regarding whom to evaluate with cardiac testing and how to best utilize CMR to confirm cardiac injury in those COVID-19-positive athletes.

Unfortunately, screening can lead to both false-positive and false-negative findings, and there are challenges with the interpretation of biomarkers, ECGs, and imaging tests in athletes in whom exercise-induced cardiac remodeling can be misinterpreted as pathology. As per the American Society of Echocardiography, optimal use of multimodality imaging in athletes requires both an understanding of expected physiologic changes in athletic hearts and the strengths and weaknesses of available imaging techniques to integrate and interpret multimodality diagnostic imaging.²⁰ With uncertainties present, management decisions regarding RTP and risk-acceptance should be made in conjunction with athletes using a patient-centered approach.

References

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Clinical Topics: Arrhythmias and Clinical EP, COVID-19 Hub, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pericardial Disease, Sports and Exercise Cardiology, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Sports and Exercise and Imaging

Keywords: COVID-19, SARS-CoV-2, Stroke Volume, Gadolinium, Heart Ventricles, Ventricular Remodeling, Contrast Media, Return to Sport, Myocarditis, Troponin, Retrospective Studies, Pericardial Effusion, Atrioventricular Block, Coronavirus, Dilatation, Ventricular Function, Left, Magnetic Resonance Imaging, Electrocardiography, Echocardiography, Death, Sudden, Cardiac, Death, Sudden, Cardiac, Athletes, Sports, Fibrosis, Heart Failure, Biopsy, Edema, Biomarkers, Reference Standards, Polymerase Chain Reaction, Patient-Centered Care, Inflammation, Probability, Chest Pain, Delivery of Health Care, Ischemia

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