Pericarditis is defined as the inflammation of the pericardial layers of the heart and is the most common manifestation of pericardial disease.¹ Inflammation of the pericardium and pericardial sac may be associated with pericardial effusion that can result in reduced cardiac filling. Although idiopathic cause is common, viruses are the most common prevalent etiologic agent in developed countries. Acute pericarditis is responsible for about 5% of the emergency room admission for chest pain in North America.²

Recently, the pandemic caused by the novel SARS-CoV-2 virus has notably affected the cardiovascular system. Viral entry to the cardiomyocyte via the angiotensin-converting enzyme 2 (ACE2) protein found cell membranes raised hypothesis about a direct cell damage. Original studies reported presence of myocarditis in up to 17% of hospitalized patients and up to 31% of those admitted to the intensive care unit.^3-5 However, recent pathologic studies found presence of the virus in the interstitial cells and macrophages, and not in cardiomyocytes,⁶ rising doubts about a direct-only viral cell damage causing myocarditis but rather a generalized organ dysfunction caused by a systemic response to the virus infection. Studies have found changes to right and left ventricular structure and function, persisting from acute stage to months following recovery.⁷

The mechanism of injury causing myocardial disease are diverse and the exact mechanism causing pericardial inflammation warrant further investigation. It remains unclear whether the pericardial disease is primarily viral or secondary to a multisystemic inflammatory syndrome.⁸

Recent studies have described angiogenesis as a cause of endothelial injury associated with intracellular SARS-CoV-2, a mechanism called intussusceptive angiogenesis.⁹ Moreover, susceptibility of mesothelial cells to COVID-19 virus may increase angiotensin-converting enzyme receptor activity in their membrane, potentially explaining the prevalence of pericardial disease.¹⁰ Although, hypothesis generating, further work is needed to better elucidate the aforementioned pathologic mechanism.

Cardiac involvement beyond the acute phase of the disease is currently under investigation. Many patients report persistence of cardiopulmonary symptoms up to 50 days after initial diagnosis.¹¹ The importance of detecting early cardiac changes is imperative in the younger population, especially young athletes who may be at risk for sports- and exercise-related arrhythmias and cardiovascular dysfunction. Even asymptomatic to mildly symptomatic patients have shown to have significant cardiac involvement associated with myocarditis.¹²

In a recent study performed by Brito et al., COVID-19 related cardiac involvement was evaluated using a multimodality approach with echocardiography, using global longitudinal strain (GLS), and cardiac magnetic resonance imaging (CMR) in a young cohort of college student athletes.¹³ The overall prevalence of cardiac findings using both modalities was 56.3%, with pericardial involvement being the most common abnormality with a prevalence of 39%, followed by myocardial involvement in 29% of cases. Interestingly, 22% of subjects with pericardial enhancement also had myocardial involvement. Specific CMR signs of myocardial inflammation (evaluated with T1 and T2 mapping sequences) were not seen in any patient. While the prevalence of cardiac manifestations in COVID-19 has varied in different studies, with some studies showing high prevalence of myocarditis or pericarditis,^7,13 others have not shown similar prevalence in convalescing patients.¹² The exact reason for this variance remains unknown and could be related to varying host and viral factors that impact disease transmission and pathogenicity.

The relationship of abnormalities seen in both imaging modalities was assessed using an unsupervised hierarchical clustering analysis. The resulting heat map was able to isolate those subjects with significant abnormalities from the rest of the group, suggesting that strain echocardiography can easily detect changes in the contractile machinery of the myocardium, a process described in subjects affected by SARS-CoV-2 virus infection.^14,15 These findings correlate strongly with those seen on CMR. Despite the significant evidence of cardiac implications seen using multimodality imaging, the exact clinical implication is yet to be evaluated with additional studies needed for comparisons among young athletes.

A recent expert consensus statement was published to guide the evaluation of cardiovascular involvement in athletes who have been infected by COVID-19.¹⁶ Routine testing is not recommended for asymptomatic individuals, unless there is evidence of abnormal electrocardiogram, elevated cardiac biomarkers (high sensitive troponin) or other clinical concerns. Transthoracic echocardiogram is the best initial imaging modality. Abnormalities within the right ventricle, left ventricle or evidence of pericardial disease may warrant further investigation with CMR. Parametric mapping and extracellular volume evaluation is recommended in the assessment of these patients. Restriction of sports-related activities should follow the current recommendation for management of patients affected with COVID-19.¹⁷

Given the rapid spread of the virus, cardiac evaluation is necessary to achieve early detection of changes suggesting cardiac involvement. Despite unclear clinical implication of cardiac findings on multimodality, early multimodality cardiac imaging to characterize the degree and type of cardiac involvement will be important potentially for risk stratification for individual patients and also widening available data to study at a population level. In addition, an understanding of genetic and non-genetic factors is important since clinical variations in the expression of SARS-CoV-2-related genes has been linked to host factors, environmental exposures, and host variations.¹⁸

We hope that in near future managing practices and long-term consequences will be assessed adequately with careful and rigorous evaluation of data acquired with the goal of aiming adequate management and improving prognosis.

References

1. Adler Y, Charron P, Imazio M, et al. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: the Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). Eur Heart J 2015;36:2921-64.
2. Chiabrando JG, Bonaventura A, Vecchie A, et al. Management of acute and recurrent pericarditis: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;75:76-92.
3. Huang L, Zhao P, Tang D, et al. Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging. JACC Cardiovasc Imaging 2020;13:2330-39.
4. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020;92:568-76.
5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62.
6. Lindner D, Fitzek A, Bräuninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol 2020;5:1281-85.
7. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19) JAMA Cardiol 2020;5:1265-73.
8. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020;383;334-46.
9. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120-28.
10. de Sousa IRF, Pereira ICC, de Morais LJ, Teodoro LGVL, Rodrigues MLP, Gomes RA. Pericardial parietal mesothelial cells: source of the angiotensin-converting-enzyme of the bovine pericardial fluid. Arq Bras Cardiol 2017;109:425-31.
11. Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603-05.
12. Rajpal S, Tong MS, Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol 2021;6:116-18.
13. Brito D, Meester S, Yanamala N, et al. High prevalence of pericardial involvement in college student-athletes recovering from COVID-19. JACC Cardiovasc Imaging 2021;14:541-55.
14. Goerlich E, Gilotra NA, Minhas AS, Bavaro N, Hays AG, Cingolani OH. Prominent longitudinal strain reduction of basal left ventricular segments in patients with COVID-19. J Card Fail  2021;27:100-04.
15. Lairez O, Blanchard V, Houard V, et al. Cardiac imaging phenotype in patients with coronavirus disease 2019 (COVID-19): results of the cocarde study. Int J Cardiovasc Imaging 2020;Sep 9:[Epub ahead of print].
16. Phelan D, Kim J, Elliott M, et al. Screening potential cardiac involvement in young athletes recovering from COVID-19: an international expert consensus statement. JACC Cardiovasc Imaging 2020;13:2635-52.
17. Wilson MG, Hull JH, Rogers J, et al. Cardiorespiratory considerations for return to play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians. Br J Sports Med 2020;54:1157-61.
18. Kasela S, Ortega VE, Martorella M, et al. Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium. Genome Med 2021;13: 66.

Clinical Topics: Arrhythmias and Clinical EP, COVID-19 Hub, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pericardial Disease, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Magnetic Resonance Imaging

Keywords: SARS-CoV-2, COVID-19, Heart Ventricles, Myocytes, Cardiac, Peptidyl-Dipeptidase A, Myocarditis, Pericardial Effusion, Troponin, Pandemics, Virus Internalization, Multiple Organ Failure, Pericarditis, Echocardiography, Magnetic Resonance Imaging, Pericardium, Arrhythmias, Cardiac, Chest Pain, Students, Inflammation, Cell Membrane, Biomarkers, Macrophages, Intensive Care Units, Cluster Analysis, Electrocardiography, Environmental Exposure, Risk Assessment, Emergency Service, Hospital

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