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      Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection : Results From the Big Ten COVID-19 Cardiac Registry

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      , MD 1 , , , MBBS, MD 1 , , , MS 2 , , MD 3 , , MD 4 , , MD 3 , , MD 3 , , DO 5 , , MD 6 , , MD 7 , , MD 8 , , DO 9 , , MD 4 , , PhD 3 , , PhD 2 , , MD 10 , , MD 11 , , MD 12 , , MD 13 , , MD 14 , , MD 15 , , MD 13 , , MD 16 , , PhD 4 , , DO 1 , , DO 17 , , MD 18 , , PhD 19 , , MD 20 , , MD 5
      JAMA Cardiology
      American Medical Association

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          Abstract

          This cohort study assesses the prevalence of myocarditis in athletes with COVID-19 and compares screening strategies for safe return to play.

          Key Points

          Question

          What is the prevalence of myocarditis in competitive athletes after COVID-19 infection, and how would different approaches to screening affect detection?

          Findings

          In this cohort study of 1597 US competitive collegiate athletes undergoing comprehensive cardiovascular testing, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%. Screening with cardiovascular magnetic resonance imaging increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4 to 2.3%.

          Meaning

          These cardiac magnetic resonance imaging findings provide important data on the prevalence of clinical and subclinical myocarditis in college athletes recovering from symptomatic and asymptomatic COVID-19 infections.

          Abstract

          Importance

          Myocarditis is a leading cause of sudden death in competitive athletes. Myocardial inflammation is known to occur with SARS-CoV-2. Different screening approaches for detection of myocarditis have been reported. The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches.

          Objective

          To determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play.

          Design, Setting, and Participants

          Big Ten COVID-19 Cardiac Registry principal investigators were surveyed for aggregate observational data from March 1, 2020, through December 15, 2020, on athletes with COVID-19. For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded. Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings. Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities. Myocarditis prevalence across universities was determined. The utility of different screening strategies was evaluated.

          Exposures

          SARS-CoV-2 by polymerase chain reaction testing.

          Main Outcome and Measure

          Myocarditis via cardiovascular diagnostic testing.

          Results

          Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [60.4%]). Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 2.3%; range per program, 0%-7.6%); 9 had clinical myocarditis and 28 had subclinical myocarditis. If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 0.31%). Cardiac magnetic resonance imaging for all athletes yielded a 7.4-fold increase in detection of myocarditis (clinical and subclinical). Follow-up CMR imaging performed in 27 (73.0%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (40.7%).

          Conclusions and Relevance

          In this cohort study of 1597 US competitive athletes with CMR screening after COVID-19 infection, 37 athletes (2.3%) were diagnosed with clinical and subclinical myocarditis. Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis. Variable ascertainment and unknown implications of CMR findings underscore the need for standardized timing and interpretation of cardiac testing. These unique CMR imaging data provide a more complete understanding of the prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection. The role of CMR in routine screening for athletes safe return to play should be explored further.

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          Most cited references40

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          Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

          Question What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)? Findings In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis. Meaning These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19). Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract. Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57). Results Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P  = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P  = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r  = 0.07; P  = .47; native T2: r  = 0.14; P  = .15; hsTnT: r  = −0.07; P  = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping ( r  = 0.33; P  < .001) and native T2 mapping ( r  = 0.18; P  = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology. Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
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            Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation

            This JACC Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation (Lake Louise Criteria) that include options to use parametric mapping techniques. While each parameter may indicate myocardial inflammation, the authors propose that CMR provides strong evidence for myocardial inflammation, with increasing specificity, if the CMR scan demonstrates the combination of myocardial edema with other CMR markers of inflammatory myocardial injury. This is based on at least one T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted CMR images), with at least one T1-based criterion (increased myocardial T1, extracellular volume, or late gadolinium enhancement). While having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one (i.e., T2-based OR T1-based) marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, albeit with less specificity. The update is expected to improve the diagnostic accuracy of CMR further in detecting myocardial inflammation.
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              Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.

              Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria").
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                Author and article information

                Journal
                JAMA Cardiol
                JAMA Cardiol
                JAMA Cardiol
                JAMA Cardiology
                American Medical Association
                2380-6583
                2380-6591
                27 May 2021
                September 2021
                27 May 2021
                : 6
                : 9
                : 1078-1087
                Affiliations
                [1 ]Division of Cardiology, Department of Internal Medicine, Ohio State University, Columbus
                [2 ]School of Public Health, Indiana University, Bloomington
                [3 ]University of Maryland School of Medicine, Baltimore
                [4 ]University of Michigan, Ann Arbor
                [5 ]Indiana University School of Medicine, Bloomington
                [6 ]University of Iowa Stead Family Children’s Hospital, Iowa City
                [7 ]Ohio State University, Columbus
                [8 ]Indiana University School of Medicine, Indianapolis
                [9 ]Michigan State University, East Lansing
                [10 ]University of Nebraska, Lincoln
                [11 ]University of Wisconsin School of Medicine, Madison
                [12 ]Purdue University, West Lafayette, Indiana
                [13 ]University of Minnesota, Minneapolis
                [14 ]Indiana University, Bloomington
                [15 ]Feinberg School of Medicine, Northwestern University, Chicago, Illinois
                [16 ]University of Maryland at College Park, College Park
                [17 ]Penn State Health Sports Medicine, State College, Pennsylvania
                [18 ]Robert Wood Johnson Medical School, Rutgers University, Newark, New Jersey
                [19 ]Rutgers Biomedical and Health Sciences, Newark, New Jersey
                [20 ]University of Nebraska Medical Center, Omaha
                Author notes
                Article Information
                Group Information: Nonauthor contributors to the Big Ten COVID-19 Cardiac Registry appear at the end of this article.
                Corresponding Author: Curt J. Daniels, MD, Division of Cardiovascular Medicine and Pediatric Cardiology, Department of Internal Medicine and Pediatrics ( curt.daniels@ 123456osumc.edu ), and Saurabh Rajpal, MBBS, MD, Division of Cardiology, Department of Internal Medicine ( saurabh.rajpal@ 123456osumc.edu ), Ohio State University, 473 W 12th Ave, Columbus, OH 43210.
                Accepted for Publication: April 21, 2021.
                Published Online: May 27, 2021. doi:10.1001/jamacardio.2021.2065
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Daniels CJ et al. JAMA Cardiology.
                Author Contributions: Dr Daniels had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Daniels, Rajpal, Rosenthal, Terrin, Jeudy, Law, Borchers, Kovacs, Kovan, Rifat, Bento, Day, Olson, Rooks, Somers, Tong, Wisinski, Womack, Kratochvil, Rink.
                Acquisition, analysis, or interpretation of data: Daniels, Rajpal, Greenshields, Rosenthal, Chung, Terrin, Jeudy, Mattson, Law, Kovacs, Rifat, Albrecht, Bento, Albers, Bernhardt, Hecht, Hipskind, Mjaanes, Olson, Rooks, Somers, Tong, Wisinski, Womack, Esopenko, Kratochvil, Rink.
                Drafting of the manuscript: Daniels, Rajpal, Greenshields, Jeudy, Kovacs, Rifat, Bento, Hecht, Mjaanes, Wisinski, Kratochvil, Rink.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Daniels, Greenshields, Rosenthal, Terrin, Albrecht, Bento, Somers.
                Obtained funding: Rajpal.
                Administrative, technical, or material support: Daniels, Rajpal, Rosenthal, Jeudy, Borchers, Kovacs, Kovan, Rifat, Hecht, Hipskind, Mjaanes, Olson, Rooks, Tong, Womack, Esopenko, Kratochvil.
                Supervision: Daniels, Rajpal, Chung, Terrin, Kovacs, Rifat, Bento, Olson, Tong, Rink.
                Conflict of Interest Disclosures: Dr Daniels reported a donation from a family fund to support the research team and regulatory work at Ohio State University. Dr Rajpal reported grants from the Jay and Jeanie Schottenstein Foundation during the conduct of the study. Dr Albers reported that their institution, the University of Nebraska, applied for $5000 from the Big Ten Conference Cardiac Registry to cover expenses incurred in the collection and submission of data; if received by the University of Nebraska, Dr Albers will not receive any of these funds. Dr Day reported support for regulatory costs from Indiana University to their institution. Dr Somers reported grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.
                Funding/Support: The Jay and Jeanie Schottenstein Family Foundation provided funding to support the collection and management and analysis of data for the Big Ten COVID-19 Cardiac Registry and the Ohio State University. The Rink Family Foundation provided funding to support the collection and management and analysis of data for the Big Ten COVID-19 Cardiac Registry. The PJ Schafer Cardiovascular Research Fund provided funding to support the collection and management and analysis of data at the University of Maryland.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Group Information: Nonauthor contributors to the Big Ten COVID-19 Cardiac Registry are listed in Supplement 3.
                Article
                hoi210042
                10.1001/jamacardio.2021.2065
                8160916
                34042947
                507e7bbc-c67f-4578-80dd-0fa4672d1662
                Copyright 2021 Daniels CJ et al. JAMA Cardiology.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 17 March 2021
                : 21 April 2021
                Funding
                Funded by: Jay and Jeanie Schottenstein Family Foundation
                Funded by: Rink Family Foundation
                Funded by: PJ Schafer Cardiovascular Research Fund
                Categories
                Research
                Research
                Original Investigation
                Online First
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