Myocarditis - Professor Richard Kirk 2023

Virtually any infective, autoimmune, drug or toxin has been implicated in the pathogenesis of myocarditis. Common viral causes and their mechanism of action are detailed in Table 1. In brief myocyte damage may be caused directly (cardiotropic and vasculotropic viruses) or indirectly (lymphotropic viruses) by infiltration of the heart. Some viruses do not infect cardiac cells but cause cardiac injury by triggering a cytokine storm or invoking an adverse cellular response. Recently Parvovirus B19, HHV6 and Coxackie B (especially in young children) are the commonest viruses.

The initial damage caused by viruses may be direct effect on the myocyte or endothelium. Following infection the virus may be cleared, persist leading to chronic or recurrent myocarditis or lie dormant without causing disease. However much of myocardial inflammation is driven by the immune response to the initial insult. Immune cells are first recruited to the myocardium during the early acute phase of infection with the innate system triggered first with neutrophils, natural killer (NK) cells, and macrophages followed later by cells of the adaptive system including T & B cells. In most patients this leads to resolution of myocarditis and clinical recovery but in some, the immune reaction is excessive or persistent, mediated by pro-inflammatory cytokines, compounding the initial damage and leading to myocardial fibrosis and end stage cardiac failure indistinguishable from idiopathic DCM.

Both cMRI and immunohistochemical pathology do however provide the best means of identifying the viral insult, the phase of myocarditis and directing management.

Specific antiviral therapy, when the features of myocarditis and replicating virus is present in the biopsy should be given. However standard qPCR for the viral genome may be positive, even of the virus is latent and, so when available, further testing for replication should be carried out utilizing technology e.g. RNAscope® able to detect single molecules necessary for viral replication. Table 1 outlines the specific antiviral treatments including Interferon dose and increasingly specific treatments are available for SARS-CoV-2. Consideration should also be given to removal of cytokines and other pro-inflammatory molecules with immunoadsorption. The anti-viral actions of interferon include direct killing, activation of antigen presenting dendritic cells, clonal  expansion of virus-specific T cells and antibody producing B cells. IVIG has several anti-viral actions including preventing cell penetration, and activating the innate immune system cells and the complement pathways and is known to have significant activities against CMV, VZV, HSV, EBV, Parvovirus B19.