Successful heart transplantation for COVID-19-associated post-infectious fulminant myocarditis

Abstract

Various clinical presentations of the 2019 coronavirus disease (COVID-19) have been described, including post-infectious acute and fulminant myocarditis. Here, we describe the case of a young patient admitted for COVID-19-associated post-infectious fulminant myocarditis. Despite optimal pharmacologic management, haemodynamic status worsened requiring support by veno-arterial extracorporeal membrane oxygenation. Emergent heart transplantation was required at Day 11 given the absence of cardiac function improvement. The diagnosis of post-infectious COVID-19-associated myocarditis was made from both pathologic examination of the explanted heart and positive SARS-CoV-2 serology.

Keywords: COVID-19; Cardiogenic shock; Extracorporeal membrane oxygenation; Fulminant myocarditis; Heart transplantation.

Figure 1

Computed tomography (CT) pulmonary angiography. (A, B) Axial CT images (lung window: W 1600/L–500 HU) show peripheral ground‐glass opacities (white arrows) suggestive of COVID‐19 pneumonia as well as right pleural effusion (black arrow) and septal lines (white arrowheads) related to a left ventricular dysfunction. (C) CT pulmonary angiogram in the coronal plane shows no pulmonary embolism. (D) Axial post‐contrast CT image shows thickening and heterogeneous enhancement of left ventricular myocardium (black arrowheads). Note pleural and pericardial effusion.

Figure 2

Cardiac magnetic resonance imaging. (A, B) Four‐chamber steady‐state free precession cine images at end‐diastole (A) and end‐systole (B) demonstrate a left ventricular dysfunction (ejection fraction: 25%) with myocardial wall thickening (17 mm), as well as bilateral pleural effusion (white arrowheads). (C, D) Four‐chamber (C) and two‐chamber (D) late gadolinium enhancement images show massive and heterogeneous enhancement of the left ventricular myocardium (white arrows). Note image artefacts related to patient's tachycardia and inability to hold the breath during cardiac magnetic resonance examination.

Figure 3

Pathological analysis of the explanted heart. Explanted heart was first fixed in 4% formalin solution for macroscopic examination. Multiple samples were then realized (on each ventricle, apex, septum, and coronary vessels), embedded in six paraffin blocks and stained with haematoxylin–eosin–saffron before microscopic examination. Special stained were used on the more representative samples (PAS, GRAM, Grocott, Ziehl), and immunohistochemistry was also performed on 4‐μm‐thick tissue sections cut and mounted on glass slides. The preparations were dried for 1 h at 58°C and overnight at 37°C. Then the tissue sections were deparaffinized with xylene, rehydrated with ethanol, and finally pretreated and immunostained using Ventana Benchmark XT® (Ventana Roche, Switzerland). Macroscopic examination showed focal fibrinous deposits on pericardium, no valvular or coronary abnormality after dissection, but haemorrhagic suffusions in the subendocardial area. Microscopic examination demonstrated a polymorphic inflammatory infiltrate, mostly in myocardium areas but focally extended to endocardium and pericardium. Lymphocytes were predominant. Infiltrate also contained plasmocytes, neutrophils, eosinophils, and histiocytic and giant cells. Clusters of neutrophils with leucocytoclasia suggested suppurated lesions. Myocardial cells were suffering with clarified cytoplasm, sometimes fibrillary or eosinophil, and with enlarged dystrophic nucleus. Large areas of necrosis and haemorrhage were seen among these inflammatory areas. Adjacent myocardium showed interstitial oedema and focally recent interstitial fibrosis. Ziehl, Grocott, Gram, and EBER ISH stains were negative. Most of lymphocytes were T phenotype CD5⁺, with only a few associated B lymphocytes CD20⁺. Numerous histiocytic cells were revealed by CD163 immunostaining. Cytomegalovirus immunostaining was negative as well as Epstein–Barr virus in situ hybridization. A (×2) and B (×20): necrosis and polymorph inflammatory infiltrate with haematic suffusion in endocardium and myocardium. C (×10) and D (×20): pericardial inflammatory reaction.

Figure 4

SARS‐CoV‐2 antibodies (Ab) evolution over time. Horizontal axis shows the dates of serum samples. Left vertical axis stands for anti‐SARS‐CoV‐2‐specific immunoglobulin M (IgM), represented with black squares. Right vertical axis stands for total anti‐SARS‐CoV‐2 antibodies, represented with white circles. The vertical dashed line represents the day of heart transplantation. Serological assays following the heart transplantation should be interpreted cautiously.