The clinicopathologic features of fulminant myocarditis

Fulminant myocarditis (FM) is the most severe form of myocarditis, characterized by rapid clinical progression and circulatory instability. However, its pathological features and their relationship to clinical presentation are not well understood.

This study aims to provide an overview of the clinicopathologic features of FM.

A total of 80 patients with FM were enrolled between January 2021 and September 2022 in Wuhan, China. Endomyocardial biopsies and subsequent histochemical staining were performed on all patients who were followed up for 3 months. The pathological features of the myocardium were described. The relationship between myocardial inflammatory cell infiltration and clinical presentation was analyzed.

According to hematoxylin and eosin staining, 76 out of 80 patients with FM were diagnosed with lymphocytic myocarditis, while 4 were diagnosed with eosinophilic myocarditis. Microscopically, various forms of cell degeneration were observed, especially myocardial edema and cardiomyocyte necrosis. Histochemical analysis indicated that innate immune cells (primarily macrophages and neutrophils) predominated in the acute stage of FM. Proper treatment with immunomodulatory agents, such as glucocorticoids and immunoglobulin, promoted macrophage polarization into the M2 subtype. A high density of total inflammatory cell infiltration was associated with elevated levels of inflammatory biomarkers (hs-CRP and ESR) and more severe circulatory deterioration, which necessitated more frequent use of IABP, ECMO, and pacemakers.

To date, this largest cohort of histochemical analyses of FM, based on endomyocardial biopsy samples, has revealed dominant infiltration of innate immune cells in the early stage, followed by lymphocytes. This finding suggests that the activation of innate immunity is the initial mechanism triggering the cytokine storm in FM. The results also support the beneficial effects of immunomodulatory therapy using glucocorticoids and immunoglobulins rather than immunosuppression by promoting M2 macrophage polarization. This study was registered at https://clinicaltrials.gov/study/NCT03268642.