https://orcid.org/0000-0003-3388-2508
Abstract
Cardiac manifest of COVID-19 infection was widely reported. The pathophysiology is thought the combination of direct damage caused by viruses and myocardial inflammation caused by immune responses. We tracked the inflammatory process of fulminant myocarditis associated with COVID-19 infection using multi-modality imaging.
A 49-year-old male with COVID-19 went into cardiac arrest from severe left ventricular dysfunction and cardiac tamponade. He was treated with steroids, remdesivir, and tocilizumab but failed to maintain circulation. He recovered with pericardiocentesis and veno-arterial extracorporeal membrane oxygenation in addition to the immune suppression treatment. In this case, a series of chest computed tomography (CT) was performed on Days 4, 7, and 18 and cardiac magnetic resonance (MR) on Days 21, 53, and 145.
Analysis of the inflammatory findings on CT in this case showed that intense inflammation around the pericardial space was observed at an early stage of the disease. Although inflammatory findings in the pericardial space and chemical markers had improved according to non-magnetic resonance imaging (MRI) tests, the MRI revealed a notable long inflammatory period more than 50 days.
Severe inflammation round the pericardium existed before appearance of pericardial fluid.
In COVID-19–associated fulminant myocarditis, recovery from myocardial damage on MRI took 145 days.
Introduction
Myocarditis has been reported to occur in severe cases of COVID-19 infection. However, there have been few reports of fulminant myocarditis, and even less is known about its clinical course. We report on a case of fulminant myocarditis and its clinical course including the inflammatory process as assessed by magnetic resonance imaging (MRI) and computed tomography (CT).
Timeline
| Symptoms | Imaging | Imaging findings | Treatment | ||
|---|---|---|---|---|---|
| Day 1 | Fever | ||||
| Day 4 | Continue fever | COVID-19 diagnosed by PCR¶ | CT† | Small amount of pericardial effusion and severe pericardial inflammation | |
| Day 7 | Worsening dyspnoea | Hospitalization | CT | Moderate amount of pericardial effusion, improved pericardial inflammation, and pneumonia | Steroid, remdesivir, and tocilizumab |
| Day 8 | Haemodynamic deterioration and subsequent cardiac arrest with pulseless electrical activity | Transfer to our hospital | V-A ECMO**, pericardiocentesis, mechanical Ventilation, CHDF*, and casirivimab/imdevimab | ||
| Day 11 | V-A ECMO discontinued | ||||
| Day 15 | Extubation | ||||
| Day 16 | CHDF discontinued | ||||
| Day 18 | CT | Small amount of pericardial effusion, improved pericardial inflammation, and resolution of pneumonia | |||
| Day 19 | MRI‖ (cine MRI and T2-WI STIR BB#) | Myocardial oedema | |||
| Day 40 | Haemodialysis discontinued | ||||
| Day 46 | Discharge | ||||
| Day 53 | MRI (cine MRI, T2-WI STIR BB, and native T1) | Improved myocardial oedema, and abnormal native T1 value | |||
| Day 145 | MRI (cine MRI, T2-WI STIR BB, native T1, LGE§, and ECV‡) | Normal native T1 value and residual LGE |
| Symptoms | Imaging | Imaging findings | Treatment | ||
|---|---|---|---|---|---|
| Day 1 | Fever | ||||
| Day 4 | Continue fever | COVID-19 diagnosed by PCR¶ | CT† | Small amount of pericardial effusion and severe pericardial inflammation | |
| Day 7 | Worsening dyspnoea | Hospitalization | CT | Moderate amount of pericardial effusion, improved pericardial inflammation, and pneumonia | Steroid, remdesivir, and tocilizumab |
| Day 8 | Haemodynamic deterioration and subsequent cardiac arrest with pulseless electrical activity | Transfer to our hospital | V-A ECMO**, pericardiocentesis, mechanical Ventilation, CHDF*, and casirivimab/imdevimab | ||
| Day 11 | V-A ECMO discontinued | ||||
| Day 15 | Extubation | ||||
| Day 16 | CHDF discontinued | ||||
| Day 18 | CT | Small amount of pericardial effusion, improved pericardial inflammation, and resolution of pneumonia | |||
| Day 19 | MRI‖ (cine MRI and T2-WI STIR BB#) | Myocardial oedema | |||
| Day 40 | Haemodialysis discontinued | ||||
| Day 46 | Discharge | ||||
| Day 53 | MRI (cine MRI, T2-WI STIR BB, and native T1) | Improved myocardial oedema, and abnormal native T1 value | |||
| Day 145 | MRI (cine MRI, T2-WI STIR BB, native T1, LGE§, and ECV‡) | Normal native T1 value and residual LGE |
*CHDF, continuous haemodiafiltration; †CT, computed tomography; ‡ECV, extracellular volume; §LGE, late gadolinium enhancement; ‖MRI, magnetic resonance imaging; ¶ PCR, polymerase chain reaction; #T2-WI STIR BB, T2-weighted image short-tau inversion recovery black blood; **V-A ECMO, veno-arterial extracorporeal membrane oxygenation.
| Symptoms | Imaging | Imaging findings | Treatment | ||
|---|---|---|---|---|---|
| Day 1 | Fever | ||||
| Day 4 | Continue fever | COVID-19 diagnosed by PCR¶ | CT† | Small amount of pericardial effusion and severe pericardial inflammation | |
| Day 7 | Worsening dyspnoea | Hospitalization | CT | Moderate amount of pericardial effusion, improved pericardial inflammation, and pneumonia | Steroid, remdesivir, and tocilizumab |
| Day 8 | Haemodynamic deterioration and subsequent cardiac arrest with pulseless electrical activity | Transfer to our hospital | V-A ECMO**, pericardiocentesis, mechanical Ventilation, CHDF*, and casirivimab/imdevimab | ||
| Day 11 | V-A ECMO discontinued | ||||
| Day 15 | Extubation | ||||
| Day 16 | CHDF discontinued | ||||
| Day 18 | CT | Small amount of pericardial effusion, improved pericardial inflammation, and resolution of pneumonia | |||
| Day 19 | MRI‖ (cine MRI and T2-WI STIR BB#) | Myocardial oedema | |||
| Day 40 | Haemodialysis discontinued | ||||
| Day 46 | Discharge | ||||
| Day 53 | MRI (cine MRI, T2-WI STIR BB, and native T1) | Improved myocardial oedema, and abnormal native T1 value | |||
| Day 145 | MRI (cine MRI, T2-WI STIR BB, native T1, LGE§, and ECV‡) | Normal native T1 value and residual LGE |
| Symptoms | Imaging | Imaging findings | Treatment | ||
|---|---|---|---|---|---|
| Day 1 | Fever | ||||
| Day 4 | Continue fever | COVID-19 diagnosed by PCR¶ | CT† | Small amount of pericardial effusion and severe pericardial inflammation | |
| Day 7 | Worsening dyspnoea | Hospitalization | CT | Moderate amount of pericardial effusion, improved pericardial inflammation, and pneumonia | Steroid, remdesivir, and tocilizumab |
| Day 8 | Haemodynamic deterioration and subsequent cardiac arrest with pulseless electrical activity | Transfer to our hospital | V-A ECMO**, pericardiocentesis, mechanical Ventilation, CHDF*, and casirivimab/imdevimab | ||
| Day 11 | V-A ECMO discontinued | ||||
| Day 15 | Extubation | ||||
| Day 16 | CHDF discontinued | ||||
| Day 18 | CT | Small amount of pericardial effusion, improved pericardial inflammation, and resolution of pneumonia | |||
| Day 19 | MRI‖ (cine MRI and T2-WI STIR BB#) | Myocardial oedema | |||
| Day 40 | Haemodialysis discontinued | ||||
| Day 46 | Discharge | ||||
| Day 53 | MRI (cine MRI, T2-WI STIR BB, and native T1) | Improved myocardial oedema, and abnormal native T1 value | |||
| Day 145 | MRI (cine MRI, T2-WI STIR BB, native T1, LGE§, and ECV‡) | Normal native T1 value and residual LGE |
*CHDF, continuous haemodiafiltration; †CT, computed tomography; ‡ECV, extracellular volume; §LGE, late gadolinium enhancement; ‖MRI, magnetic resonance imaging; ¶ PCR, polymerase chain reaction; #T2-WI STIR BB, T2-weighted image short-tau inversion recovery black blood; **V-A ECMO, veno-arterial extracorporeal membrane oxygenation.
Case presentation
A 49-year-old male was transferred to our hospital for treatment of COVID-19 infection. The patient had been diagnosed with COVID-19 by PCR test (Roche Cobas 6800 SARS-CoV-2 test, Roche Molecular Systems, Branchburg, NJ) for a fever that persisted for 4 days and then was hospitalized for new-onset dyspnoea, and the finding of pneumonia by chest X-ray and pericardial and pleural effusions by CT. He needed oxygen administration by nasal cannula. A blood test revealed an elevated CPR of 7.51 mg/dL [reference range (RR): <0.14 mg/dL]. He was treated with dexamethasone 6.6 mg, remdesivir 200 mg, tocilizumab 640 mg, and heparin 1 day before being transferred to our hospital. However, the day after transfer, the patient complained of orthopnoea and needed use of a reservoir mask to maintain oxygen saturation. A chest X-ray revealed congestion of the lungs and the C-reactive protein (CRP) worsened to 10.5 mg/dL. His systolic blood pressure eventually dropped below 100 mmHg, and norepinephrine was required to maintain the blood pressure (Timeline).
Shortly after arrival at our emergency department, the patient went into circulatory collapse and subsequent cardiac arrest with pulseless electrical activity. Point-of-care echocardiography showed cardiac tamponade with a moderate amount (1.5–2.0 cm) of pericardial effusion (Figure 1A). Cardiopulmonary resuscitation failed to achieve return of spontaneous circulation (ROSC), but pericardiocentesis did (Figure 1B). Serosanguinous fluid of 350 mL was drained by pericardiocentesis. However, because his haemodynamic and respiratory status remained severely unstable, he was put on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and mechanical ventilation.
Echocardiogram, and pericardial fluid. (A) Echocardiogram in subcostal view shows a moderate amount of pericardial effusion around the ventricle (arrows) at the time of admission. (B) Pericardial fluid. Serosanguinous fluid of 350 mL was drained. (C) Twelve-lead electrocardiogram demonstrated ST elevation and low voltage in the majority of leads. (D and E) Echocardiogram in systole and diastole, respectively, after veno-arterial extracorporeal membrane oxygenation was started. Increased myocardial thickness in all segments, reduced ejection fraction, and continuing pericardial effusion are observed. (F and G) Echocardiogram in systole and diastole, respectively, on the 11th day after admission. Myocardial thickness in all segments, ejection fraction, and pericardial effusion are improved. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
Physical examination demonstrated bilateral coarse crackles, no heart murmur, and no leg oedema.
Electrocardiogram revealed sinus tachycardia, low voltage in limb leads, and ST elevation in all leads except aVR (Figure 1C). Blood tests showed elevated high-sensitivity cardiac troponin I (3132 ng/L; RR: <70 ng/L) and N-terminal brain natriuretic peptide (16 860 pg/mL; RR: <125 pg/mL). Blood and pericardial effusion test results are shown in Table 1.
Laboratory findings of blood and pericardial effusate on Day 8
| Value | Reference range | ||
|---|---|---|---|
| Blood | hs-TropI | 3132 | <70 ng/L |
| CK | 1803 | <248 U/L | |
| CK-MB | 79 | <12 U/L | |
| NT-pro BNP | 16 860 | <125 p/mL | |
| Creatinine | 3.7 | <1.0 mg/dL | |
| LDH | 4985 | <222 IU/L | |
| CRP | 8.85 | <0.14 mg/dL | |
| Ferritin | 71 120 | <465 ng/mL | |
| IL-6 | 75 | <7.0 pg/dL | |
| Pericardial effusate | LDH | 302 | |
| IL-6 | 7120 |
| Value | Reference range | ||
|---|---|---|---|
| Blood | hs-TropI | 3132 | <70 ng/L |
| CK | 1803 | <248 U/L | |
| CK-MB | 79 | <12 U/L | |
| NT-pro BNP | 16 860 | <125 p/mL | |
| Creatinine | 3.7 | <1.0 mg/dL | |
| LDH | 4985 | <222 IU/L | |
| CRP | 8.85 | <0.14 mg/dL | |
| Ferritin | 71 120 | <465 ng/mL | |
| IL-6 | 75 | <7.0 pg/dL | |
| Pericardial effusate | LDH | 302 | |
| IL-6 | 7120 |
CK, creatinine kinase; CK-MB, creatinine kinase MB isoenzyme; CRP, C-reactive protein; hs-TropI, high-sensitivity troponin I; IL-6, interleukin 6; LDH, lactate dehydrogenase; NT-proBNP, N-terminal pro-brain natriuretic peptide.
Laboratory findings of blood and pericardial effusate on Day 8
| Value | Reference range | ||
|---|---|---|---|
| Blood | hs-TropI | 3132 | <70 ng/L |
| CK | 1803 | <248 U/L | |
| CK-MB | 79 | <12 U/L | |
| NT-pro BNP | 16 860 | <125 p/mL | |
| Creatinine | 3.7 | <1.0 mg/dL | |
| LDH | 4985 | <222 IU/L | |
| CRP | 8.85 | <0.14 mg/dL | |
| Ferritin | 71 120 | <465 ng/mL | |
| IL-6 | 75 | <7.0 pg/dL | |
| Pericardial effusate | LDH | 302 | |
| IL-6 | 7120 |
| Value | Reference range | ||
|---|---|---|---|
| Blood | hs-TropI | 3132 | <70 ng/L |
| CK | 1803 | <248 U/L | |
| CK-MB | 79 | <12 U/L | |
| NT-pro BNP | 16 860 | <125 p/mL | |
| Creatinine | 3.7 | <1.0 mg/dL | |
| LDH | 4985 | <222 IU/L | |
| CRP | 8.85 | <0.14 mg/dL | |
| Ferritin | 71 120 | <465 ng/mL | |
| IL-6 | 75 | <7.0 pg/dL | |
| Pericardial effusate | LDH | 302 | |
| IL-6 | 7120 |
CK, creatinine kinase; CK-MB, creatinine kinase MB isoenzyme; CRP, C-reactive protein; hs-TropI, high-sensitivity troponin I; IL-6, interleukin 6; LDH, lactate dehydrogenase; NT-proBNP, N-terminal pro-brain natriuretic peptide.
Echocardiography revealed an increased left ventricle (LV) wall thickness (21 mm) in all segments, diffused hypokinetic LV wall motion [left ventricular ejection fraction (LVEF) = 32% by modified Simpson method] and decreased right ventricle (RV) function [fractional area change (FAC) = 11%] (Figure 1D and 1E, and see Supplementary material online, Video S1).
For drug therapy, a steroid pulse of 500 mg of methylprednisolone was used on the day of admission to our hospital. Starting the next day, the patient received treatment with intravenous prednisolone of 80 mg/day for 7 days and then at 40 mg/day for 7 days. After these 15 days of intravenous administration, prednisolone was switched to oral form, initial dose 40 mg/day, and decreased by 5 mg/day, every 2 weeks for a total of 16 weeks. In addition to the steroid pulse, heparin was continued until Day 16, and a single dose of casirivimab/imdevimab was given on Day 8. Persistent anuria after admission necessitated renal replacement therapy (RRT) with continuous haemodiafiltration.
Serial transthoracic echocardiography demonstrated gradual improvement of LV systolic function (LVEF = 45%), LV wall thickness, RV function (FAC = 26%), and reduction of pericardial fluid (Figure 1F and 1G, and see Supplementary material online, Video S2). After 3 days, V-A ECMO was discontinued, and the patient was extubated 4 days later. Serum CRP was near normal on Day 18 (0.31 mg/dL). Exacerbation of pneumonia was not observed after admission. Renal replacement therapy was switched to haemodialysis on Day 16 and discontinued on Day 40. The patient was discharged on Day 46 of onset of symptoms with normal LVEF according to echocardiographic assessment. One year after hospital discharge, no cardiovascular events have been observed.
Cardiac magnetic resonance was performed on Day 19 [cine MRI and T2-WI short-tau inversion recovery black blood (T2-WI STIR BB)], Day 53 (cine MRI, T2-WI STIR, and native T1 mapping), and Day 145 [cine MRI, T2-WI STIR, native T1 mapping, late gadolinium enhancement (LGE), and extracellular volume (ECV)] to evaluate the myocardium. Contrast agent MRI was not used for the first two MRI because of renal impairment. T2-WI SITR BB image demonstrated myocardial oedema on Day 19 and improvement after 34 days. Native T1 value was still high on Day 53 but recovered to normal range on Day 145. Subepicardial LGE was observed inferoseptally in the LV (Figure 2). The ECV mapping displayed mildly raised values but was difficult to interpret in isolation. According to the cine MRI, LVEF was 60% on Day 145. These findings met the Lake Louise Criteria on MRI1 for diagnosis of myocarditis.
Magnetic resonance imaging findings. T2-weighted image short-tau inversion recovery black blood demonstrated myocardial oedema improvement over the 145-day course. Native T1 value was slightly elevated on Day 53 and improved to normal range in 145 days. A small amount of late gadolinium enhancement and increased extracellular volume area were observed in the left ventricle inferoseptally (red arrowhead). The range of normal native T1 values of the magnetic resonance imaging scanner was 1237.8 ± 62.2. LGE, late gadolinium enhancement; T2-WI STIR BB, T2-weighted short-tau inversion recovery black blood.
Chest CT was performed on Days 4, 7, and 18. Amount of pericardial inflammatory adipose tissue was highest, and its CT value was lowest 4 days before admission to our hospital (Figure 3).
Computed tomography findings. Pericardial inflammatory adipose tissue on Days 4(A), 7(B), and 18(C). Inflammatory adipose tissue is highlighted in green (computed tomography value −180 to −40 HU) in the images. Volume and mean computed tomography value are given in the table.
Discussion
Various types of myocardial injury associated with COVID-19 have been reported. Magnetic resonance imaging findings suggestive of myocarditis have been reported in 27% of COVID-19 patients with troponin elevation. Pericardial effusion has also been observed in 5% of COVID-19 patients.2 Myocardial damage from COVID-19 infection including pericardial effusion and myocarditis has been attributed to both inflammatory reaction to the virus and damage caused by the virus itself.3
Complications of fatal pericarditis and pericardial effusion resulting in cardiac tamponade have also been reported.4–6 Reports of MRI findings in fulminant myocarditis associated with COVID-19 including cases confirmed by endomyocardial biopsy7 or diagnosed by Lake Louis Criteria based on MRI findings,8 requiring mechanical circulation support, have been few.
The time from the onset of symptoms to accumulation of pericardial fluid was a week in our case but has been as long as a month according to reports.4 Analysis of the inflammatory findings on CT in this case showed that inflammation around the pericardial space had existed as early as 4 days after the onset of symptoms. This suggested that the inflammatory process had started in the very early stage of the disease and was more intense the day before admission to our hospital than after, when pericardial effusion appeared. Interleukin 6 was elevated in the pericardial fluid as well as in the blood at the time of admission, confirming the inflammatory findings around the pericardium seen on CT.9 There was no re-accumulation of pericardial fluid, and there was a decreased amount of pericardial inflammatory adipose tissue on CT, likely due to immunosuppression therapy begun after admission to suppress inflammation.
Once the patient recovered from the critical phase and MRI could be obtained, we were able to evaluate myocardial status.
Although inflammatory findings in the pericardial space and chemical markers had improved according to non-MRI tests, the MRI revealed a notable long inflammatory period as shown in Figure 1. In particular, it was not until after 3 months that the native T1 value recovered to within the institutional standard range, at which point a small amount of LGE accumulation was observed. Repeat MRI has been recommended to be performed at least 4 weeks after initial evaluation to determine recovery from COVID-19 cardiomyopathy,10 but in our case, myocardial oedema was still present at 4 weeks. We believe myocardial damage likely persists for much longer than 4 weeks after recovery from COVID-19, especially for severe myocarditis such as in the present case.
Computed tomography imaging led to discovery of unexpected pronounced inflammation in the pericardial space in the early stage of the patient’s infection. This led to earlier than usual adoption of immunosuppressive therapy, which was likely beneficial for this patient. MRI, in contrast, cannot guide therapy in the acute phase of severe COVID-19 infections, because of its impracticality in critical care scenarios. However, we were able to confirm, through the use of MRI, how well application of therapy developed for COVID-19 pneumonia including immunosuppressive therapy worked for the patient’s fulminant myocarditis. This is an important finding because there is currently no established therapeutic protocol for the treatment of fulminant myocarditis owing to its rarity. Although it is only one instance, our case supports the application of immunosuppressive therapy to future fulminant myocarditis cases.
Conclusion
We report a case of severe COVID-19 infection that displayed pericardial effusion and fulminant myocarditis whose course of inflammatory process we were able to track with extensive and frequent multimodal imaging.
Lead author biography
Satoshi Hara obtained his medical degree in 2012. He is currently working as a EP fellow at the Tsuchiura Kyodo Hospital.
Supplementary material
Supplementary material is available at European Heart Journal – Case Reports.
Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.
Consent: The patient has given written informed consent for publication in accordance with COPE guideline.
Funding: None declared.
References
Author notes
Conflict of interest: None declared.
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