COVID-19 vs. Classical Myocarditis Associated Myocardial Injury Evaluated by Cardiac Magnetic Resonance and Endomyocardial Biopsy

Figure 1. Schematic representation of cardiac magnetic resonance (CMR) protocol workflow used for our study, in keeping with recent SCMR recommendations for evaluation of patients with COVID-19 (18).

Figure 2. Left ventricle (LV, upper row) and right ventricular (RV, lower row) ejection fraction (EF), end diastolic volume (EDV), and myocardial mass in three pathology groups (from left to right: Control, COVID-19, and Myocarditis). There is no difference on average between patients with COVID-10 and Controls. However, there is significant dysfunction and remodeling in some of these patients that overlaps with the myocarditis spectrum. A p < 0.05 was considered statistically significant, and indicated as follows: * < 0.05, ** < 0.01. *** < 0.001.

Figure 3. Parametric Imaging in three pathology groups (from left to right: Control, COVID-19, Myocarditis): (A) T1 native, (B) Extracellular volume (ECV)–for the Control it is represented the mean and SD referenced in literature [Dabir et al., (24)] corresponding to similar manufacturer and magnet field strength, (C) T2. A p < 0.05 was considered statistically significant, and indicated as follows: * < 0.05, ** < 0.01, *** < 0.001.

Figure 4. Lake Louise Criteria (LLC) and Functional Impairment in patients with COVID-19 and patients with Myocarditis. (A) Comparison of the CMR LLC and endomyocardial biopsy (EMB) findings. Three out of 32 (9%) patients with COVID-19 and all 22 (100%) of the patients with myocarditis have positive LLC, (B) from the patients in which endomyocardial biopsy (EMB) was available: none of the patients with COVID-19 and 13 (87%) out of 15 patients with myocarditis with available EMB had histological findings in keeping with this diagnosis, 1 (10%) of the patients with COVID-19, and 2 (13%) of the patients with myocarditis have positive LLC but negative EMC diagnostic criteria. (C) tables with numeric values for CMR LLC (upper rows) and Endomyocardial Biopsy Analyses (lower rows) (D) spidernet representation of myocardial inflammation, injury, pericardial involvement, LV, and RV dysfunctions in all COVID-19 (blue polygons) and all Myocarditis (red polygons) patients, (E) (baseline), (F) (follow-up)–spidernet representations of myocardial inflammation, injury, pericardial involvement, LV, and RV dysfunctions in patients with COVID-19 (blue polygons) and Myocarditis (red polygons) with an…

Figure 5. Exemplary EMB and CMR findings in COVID-19 (left) and Myocarditis (Right). First four rows from top represent respectively: Masson Trichrome, hematoxylin/eosin and immunohistological stainings of CD3+ T cells and CD68+ macrophages. In myocarditis, numerous T cells and macrophages are detected in presence of myocyte necrosis and fibrosis. In contrast, the majority of patients with COVID-19 often show fibrosis but no myocyte necrosis or significant T cell infiltration. However, the number of macrophages is enhanced (x400). Bottom row represents CMR short-axis late gadolinium enhancement (LGE) images: there is evidence of fibrosis in the lateral wall (indicated by the red arrow) in patients with myocarditis (right), while in COVID-19 there are no LGE positive areas in keeping with the absence of active inflammation and fibrosis indicated by the histology.

Figure 6. Comparison between LV and RV function and mass at baseline and follow-up in patients with COVID-19 and Myocarditis. On the left column, patients with COVID-19: (A) LV EF, (C) RV EF, (E) LV Mass, (G) RV Mass, (I) LV EDV, (K) RV EDV, and, on the right column, patients with Myocarditis: (B) LV EF, (D) RV EF, (F) LV Mass, (H) RV Mass, (J) LV EDV, (L) RV EDV. A p < 0.05 was considered statistically significant and indicated as follows: * < 0.05, ** < 0.01, *** < 0.001.

Figure 7. Parametric Imaging at baseline and follow-up in COVID-19 (upper row): (A) T1 native, (B) ECV and Myocarditis (lower row): (C) T2, (D) T1 native, (E) ECV, (F) T2. A p < 0.05 was considered statistically significant, and indicated as follows: * < 0.05, ** < 0.01, *** < 0.001.

Figure 8. Representative baseline and follow-up CMR images of two patients with COVID-19 (COVID-19 patient 1 with a WHO-score: mild and COVID-19 patient 2 with a WHO-score: severe and a patient with Myocarditis. Rows (from top to bottom): SSFP-cine images, T1 native maps, T2 maps, Extracellular volume maps, late gadolinium enhancement images. While in the first patient with COVID-19 (first and second columns from the left), T1 native (from 1,250 to 1,238ms), and T2 (from 60 to 50 ms) signals improved at follow-up in the second patient with COVID-19 (third and fourth columns) T1 native signal improved (from 1,306 to 1,187 ms) while T2 (from 50 to 61ms) and ECV (from 22 to 26%) worsened. In the patient with myocarditis (fifth and sixth columns) there is at follow-up a marked improvement in all the parameters.