Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes

Figures

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  Fig. 1. Different pathological phenotype of FM. a–c representative HE staining of EMB samples of FM patients showed lymphocyte FM (a), eosinophilic FM (b), and giant cell FM (c). d–f IHC staining showed massive T lymphocyte (CD45RO) infiltrated into myocardium (d). Macrophage (CD68) can also be observed (e). Few B lymphocyte (CD20) can be seen in EMB samples (b). Figure 1d–f is from ref. 130 with the permission of Circulation Journal; Fig. 1b is from ref. 153 with the permission of ESC Heart Failure; Fig. 1c is from ref. 49 with the permission of BMJ Case Report

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  Fig. 2. Cytokine storm of FM patients. Changed cytokines and their cellular origination. After scanning for changed cytokines, their immune cellular origin was searched using the Human Protein Atlas database (http://www.proteinatlas.org). Neutrophils and monocytes accounted for the majority of elevated cytokines and the majority of known immune cells participated in the dysregulation of cytokine profile

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  Fig. 3. Illustration of signaling transduction in the development of a cytokine storm in FM and potential cardiac effects. Various etiologies trigger inflammatory signaling that result in transcription and translation of pro-inflammatory cytokines. Secreted cytokines activate numerous pathways via specific receptors leading to different cellular responses. Pathogens (e.g., viruses) can directly target cells resulting in marked damage worsening the prognosis of FM patients

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  Fig. 4. Representative echocardiography and CMR assessment images of clinical FM patients. a regional strain distribution of FM patients on the day of admission, the fifth day and tenth day of hospitalization. Note the regional strain distribution improved following appropriate treatment under the guidance of life support-based comprehensive treatment regimen. b Representative CMR image of FM patients. T2WI showed left ventricular hypertrophy and massive left ventricular wall edema (red arrow) in a 37-year-old FM female patient. The middle section of apex and left ventricular wall showed late gadolinium enhancement (LGE) signal (white arrow), which indicates massive myocardial injuries. c, d Representative CMR image of a FM patient (c) and a non-fulminant myocarditis patient (d). Note the increased diffuse LGE pattern of FM compared to non-FM patient. Longer native T1 and T2 and higher extracellular volume fraction (ECV) were observed in FM patients. Figures 4c and d is from ref. 104 with the permission of the Journal of Magnetic Resonance Imaging

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  Fig. 5. The prognosis of FM patients. a The 60-day follow-up and b long-term (7 years) follow-up of FM patients in the work of Ammirati.45 These two figures are of the permission of the Journal of the American College of Cardiology. c The cumulative non-heart failure rate curve of 105 patients who were treated at Tongji hospital between January 2015 and August 2019. These patients were diagnosed as acute myocarditis (n = 54) or fulminant myocarditis (n = 51). The primary endpoint was cardiac death or heart transplantation, and the secondary endpoint was left ventricular dysfunction evidenced by ejection fraction <55% during study follow-up. The Kaplan–Meier method was used to operate the survival curve. The heart failure rate of FM patients was significantly different from that of patients with acute myocarditis (Log rank = 0.009)

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  Fig. 6. Illustration of different regimens to FM. The age of drug therapy (a), the age of MCS therapy (b), and the age of comprehensive therapy (c) carry out different interference methods. The red line represents cytokine level while the red dot line represents possible cytokine level. The blue line represents heart function, and the blue dot line represents possible future heart function manifestations. Note that heart function may deteriorate and lead to death (purple dot line)

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  Fig. 7. Illustration of the relationship of cytokine storm and immunomodulation. The cytokine storm does not necessarily equal to the elevation of absolute quantification of certain cytokine, but is more likely to be the disturbance of immunohomeostasis. The effect of immunomodulation is to restore immunohomeostasis and calm down overreacted immune response

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  Fig. 8. Flow chart of treating FM under the guidance of “life support-based comprehensive treatment regimen”