COVID-19 Myopericarditis

Quick Takes

  • Myocardial injury in COVID-19 infection is common, although clinical myocarditis is uncommon.
  • Approximately 10% of cases of COVID-19-associated myocarditis have pericardial involvement with pericardial effusion.
  • Current data suggests that the effusate seen in COVID-19 pericardial effusions is sterile, suggesting a secondary inflammatory process, rather than pericardial infection.

Background
The novel coronavirus SARS-CoV-2 was first identified in late 2019 in Wuhan province, China. Infection with SARS-CoV-2 results in the clinical syndrome of COVID-19. The vast majority of infections result in mild febrile coryzal or asymptomatic disease, particularly in young patients without comorbidity. Approximately 1% of cases require hospital admission and of these, up to a quarter will require admission to an intensive care unit for ventilatory support. The overall mortality for patients admitted to hospital is approximately 25%.1

It is now well-established that patients with a greater burden of comorbidities are at higher risk for hospitalization or death from COVID-19. In addition to conditions such as immunosuppression, active cancer, and pre-existing respiratory pathology, cardiovascular comorbidities are also important, particularly diabetes mellitus and hypertension. Published data from our center suggest that 75% of patients admitted to hospital with COVID-19 had one or more comorbidity, the commonest of which included hypertension (51%), diabetes (30%) and pre-existing cardiac disease (ischemic heart disease or heart failure, 22%).1

Myocardial Injury in COVID-19 versus Myocardial Involvement
A significant proportion of patients admitted to hospital with COVID-19 have a raised serum troponin level, and this is associated with an adverse outcome.2 There are a number of potential mechanisms for a raised troponin elevation in this population, however many of these represent indirect effects of COVID-19 on the heart (e.g. RV strain due to lung involvement and/or pulmonary emboli, a type 2 myocardial infarction due to hypoxemia or secondary to a systemic inflammatory response), rather than direct myocardial injury or inflammation causing myocarditis.

We recently described a case of COVID-19 myopericarditis with an associated pericardial effusion and cardiac tamponade.3 The initial diagnosis of COVID-19 myocarditis was made clinically, with evidence of worsening left ventricular (LV) function, in association with a positive RT-PCR for SARS-CoV-2 RNA. Due to hemodynamic embarrassment, an emergency pericardial drain was inserted (in the intensive care unit [ICU] side room). Pericardiocentesis resulted in immediate hemodynamic improvement. Analysis of the pericardial fluid revealed a sterile exudate, which was negative for SARS-Cov-2 RNA. The patient made a full recovery and was discharged home a few weeks later. A subsequent cardiac magnetic resonance imaging (MRI) scan confirmed edema and patchy non-ischemic late enhancement in the LV lateral wall, findings consistent with the diagnosis of acute myocarditis.

In a second case, a patient with previous cardiac surgery to repair congenital heart disease presented with COVID-19. An echocardiogram demonstrated a large pericardial effusion with echocardiographic evidence of tamponade. Serum hsTnT was significantly raised but LV function was preserved on echocardiogram. Due to hypotension unresponsive to intravenous fluid, the patient underwent pericardiocentesis. The drained fluid was negative for SARS-Cov-2 RNA. The patient made a full recovery and was discharged from hospital alive.

A small Italian case series of ten patients referred for cardiac MRI due to a clinical syndrome consistent with myocarditis (chest pain, raised troponin, unobstructed coronary arteries) found that eight out of ten patients had MRI findings consistent with an acute myocarditis.4 Of interest, in these patients, late gadolinium enhancement (LGE) was either absent or only present in minimal amounts, suggesting that the degree of myocardial necrosis is relatively mild, as in our case.

Further insights are provided by studies in COVID-19 survivors. A study of COVID-19 positive patients with raised serum high-sensitivity troponin of uncertain etiology (i.e. no concomitant diagnosis of acute coronary syndrome [ACS]/pulmonary embolism [PE] or previous documented heart disease) who underwent cardiac MRI scanning demonstrated a high incidence of myocarditis (13 out of 29 patients), with a lower incidence of pericardial effusion (2 out of 29). Overall, this represents a diagnosis of myocarditis in 1-2% of the total number of RT-PCR positive patients at that center, with pericardial effusion seen in approximately 10% of patients with COVID-19 myocarditis.5 These data are consistent with unpublished data from our center. Furthermore, a German cohort of 100 patients recently recovered from COVID-19 demonstrated that 60% of patients had evidence of myocardial inflammation. Of those, 70% had a detectable troponin T level (hsTnT >3pg/mL) while 5% had a troponin raised above the reference range (>13.9 pg/mL). Additionally, overall 20% had a pericardial effusion >1cm.6

Endomyocardial Biopsy
The gold-standard for diagnosis of myocarditis is through histological examination of myocardium obtain via endomyocardial biopsy (EMB). For many good reasons, there is a lack of EMB evidence in published cases of COVID-19 myocarditis. A diagnosis of myocarditis can be made in the absence of EMB evidence. This generally requires an appropriate clinical syndrome along with evidence of myocardial edema, high T2 signal and non-ischemic late enhancement on cardiac MRI.

There are practical considerations to be taken into account when considering EMB in patients with COVID-19. The patient may be critically ill and therefore too unstable for transfer to the cardiac catheterization laboratory (this was the case with our patient). Moreover, infection control procedures may preclude movement of an infected patient through the hospital. Therefore, not only may EMB be rendered not possible, but emergency procedures such as pericardiocentesis may have to be performed without benefit of fluoroscopy, using only bedside echocardiographic guidance.

Limited numbers of case series report tissue diagnoses of COVID-19 myocarditis, both pre- and post-mortem. Electron microscopy has confirmed presence of viral particles in the myocardium of a critically unwell COVID-19 patient who required ECMO support.7 Furthermore, a case series from Germany reports the detection of SARS-CoV-2 nucleic acid in the myocardium of two patients.8 Of interest, the latter case series labelled their patients as "borderline" myocarditis on the basis of limited myocardial necrosis (the predominant feature was myocardial inflammation).

Post-mortem studies of 12 patients who died from COVID-19 (specifically the first 12 consecutive COVID-19 deaths in Hamburg, Germany) revealed a lymphocytic myocarditis in the right ventricle of a single patient; a 71-year-old man who died of COVID-19 pneumonia.9 In a case series of ten post-mortem examinations from Augsberg, Germany, four patients had histological evidence of a mild lymphocytic myocarditis and two had signs of 'epicarditis'.10

More recently, a further case series from Hamburg reports an analysis of cardiac tissue from 39 consecutive autopsies in elderly COVID-19 patients. SARS-Cov-2 RNA was detected in the myocardium of 24 patients.11 However, although in situ hybridization confirmed interstitial viral presence (and evidence of viral replication in cases of high viral load), there was no evidence of viral presence in cardiomyocytes. Furthermore, there was a lack of massive cell infiltration or evidence of cardiac necrosis, therefore it was concluded that no myocarditis was present.

Pericardial Fluid Analysis of Effusate
Meta-analysis suggests that approximately 5% of patients with COVID-19 who undergo computed tomography (CT) chest for clinical indications have a detectable pericardial effusion.12 Analysis of aspirated pericardial fluid is important in the investigation of any patient with cardiac tamponade. In our center, all of the pericardial fluid samples taken from COVID-19 pericardial effusions were negative for SARS-CoV-2. This is consistent with other isolated case reports,13,14 but at odds with a case report from Lecco, Italy, where the pericardial fluid of one patient with COVID-19 tested positive for SARS-CoV-2 RNA (but only one out of three viral genes, suggesting a low viral load).15 Further case reports did not comment on whether the aspirated sample was infected or sterile16 or stated that testing for SARS-CoV-2 RNA was not possible at their center.17,18

COVID-19 Associated Myopericarditis: Key Lessons
Based on the King's College Hospital (London, UK) experience and the current literature, we believe the following can be stated:

  • Myocardial inflammation is common in COVID-19, based on troponin and cardiac MRI findings. However, this appears to be generally mild and the long-term implications of any MRI abnormalities in patients recovered from COVID-19 are yet to be determined. Life-threatening myopericarditis can occur but is rare.
  • The degree of cardiac involvement is not necessarily related to the severity respiratory involvement, i.e. a patient can be extremely unwell with COVID-19 associated myopericarditis, yet have relatively little lung involvement, as was the case with the first case at our institution.3
  • Pericardial fluid is typically exudative and free of virus, therefore likely representing an inflammatory, rather than infectious process. Furthermore, the degree of pericardial inflammatory response (and therefore size/volume of effusion) does not necessarily correlate with the degree of myocardial involvement, i.e. a large pericardial effusion with tamponade can be seen in the absence of severe/fulminant myocarditis.
  • Patients with previous cardiac disease and/or a structurally abnormal heart may be at increased risk of developing COVID-19 myopericarditis and cardiac tamponade.

 

References

  1. Bean DM, Kraljevic Z, Searle T, et al. ACE-inhibitors and angiotensin-2 receptor blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust. Eur J Heart Fail 2020;Jun 2:[Epub ahead of print].
  2. Santoso A, Pranata R, Wibowo A, Al-Farabi MJ, Huang I, Antariksa B. Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: a meta-analysis. Am J Emerg Med 2020;Apr 19:[Epub ahead of print].
  3. Hua A, O'Gallagher K, Sado DByrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J 2020;41:2130.
  4. Esposito A, Palmisano A, Natale L, et al. Cardiac magnetic resonance characterization of myocarditis-like acute cardiac syndrome in COVID-19. JACC Cardiovasc Imaging 2020;Jun 23:[Epub ahead of print].
  5. Knight DS, Kotecha T, Razvi Y, et al. COVID-19: myocardial injury in survivors. Circulation 2020;142:1120-2.
  6. 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;Jul 27:[Epub ahead of print].
  7. Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020;22:911-5.
  8. Wenzel P, Kopp S, Gobel S, et al. Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab. Cardiovasc Res 2020;Jun 20:[Epub ahead of print].
  9. Wichmann D, Sperhake JP, Lutgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19. Ann Intern Med 2020;May 6:[Epub ahead of print].
  10. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA 2020;Jun 23:[Epub ahead of print].
  11. Lindner D, Fitzek A, Brauninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol 2020;Jul 27:[Epub ahead of print].
  12. Bao C, Liu X, Zhang H, Li Y, Liu J. Coronavirus disease 2019 (COVID-19) CT findings: a systematic review and meta-analysis. J Am Coll Radiol 2020;17:701-9.
  13. Derveni V, Kaniaris E, Toumpanakis D, et al. Acute life-threatening cardiac tamponade in a mechanically ventilated patient with COVID-19 pneumonia. IDCases 2020;21:e00898.
  14. Fox K, Prokup JA, Butson K, Jordan K. Acute effusive pericarditis: a late complication of COVID-19. Cureus 2020;12:e9074.
  15. Farina A, Uccello G, Spreafico M, Bassanelli G, Savonitto S. SARS-CoV-2 detection in the pericardial fluid of a patient with cardiac tamponade. Eur J Intern Med 2020;76:100-1.
  16. Allam HH, Kinsara AJ, Tuaima T, Alfakih S. Pericardial fluid in a COVID-19 patient: is it exudate or transudate? Eur J Case Rep Intern Med 2020;7:001703.
  17. Asif T, Kassab K, Iskander F, Alyousef T. Acute pericarditis and cardiac tamponade in a patient with COVID-19: a therapeutic challenge. Eur J Case Rep Intern Med 2020;7:001701.
  18. Dabbagh MF, Aurora L, D'Souza P, et al. Cardiac tamponade secondary to COVID-19. JACC Case Rep 2020;2:1326-30.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Pericardial Disease, Cardiac Surgery and Heart Failure, Interventions and ACS

Keywords: Pericardial Effusion, Myocarditis, COVID-19, Coronavirus, Coronavirus Infections, severe acute respiratory syndrome coronavirus 2, Cardiac Tamponade, Troponin T, Pericardiocentesis, Contrast Media, Gadolinium, Patient Discharge, Acute Coronary Syndrome, Myocytes, Cardiac


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