Republished: pathogenesis and diagnosis of myocarditis

Abstract

Acute myocarditis is an inflammatory disease of the heart muscle that may progress to dilated cardiomyopathy and chronic heart failure. A number of factors including the sex hormone testosterone, components of innate immunity, and profibrotic cytokines have been identified in animal models as important pathogenic mechanisms that increase inflammation and susceptibility to chronic dilated cardiomyopathy. The clinical presentation of acute myocarditis is non-specific and mimics more common causes of heart failure and arrhythmias. Suspected myocarditis is currently confirmed using advanced non-invasive imaging and histopathologic examination of heart tissue. However, the diverse presentations of myocarditis and the lack of widely available, safe, and accurate non-invasive diagnostic tests remain major obstacles to early diagnosis and population based research. Recent advances in the understanding of disease pathogenesis described in this review should lead to more accurate diagnostic algorithms and non-invasive tests.

Figure 1

Pathogenic mechanisms in myocarditis and dilated cardiomyopathy (DCM). The incidence and severity of myocarditis and DCM is greater in men than women (and male and female mice). Studies in animal models of myocarditis show that testosterone drives the inflammation and remodelling that allows progression to DCM. Infection is a major source of cardiac injury that activates innate immune mechanisms like Toll-like receptor (TLR) 2 and TLR4 on mast cells and macrophages. Innate immunity is a dominant feature during acute myocarditis, where TLR2 and TLR4 levels remain elevated in the heart and induce proinflammatory cytokines like tumour necrosis factor (TNF) and interleukin 1β (IL1β). TNF and IL1β directly alter cardiac function and promote extracellular matrix remodelling, resulting in fibrosis and cardiac dilation. Cytokines and immune cells associated with an adaptive T helper (Th)2 type immune response, such as IL4 and alternatively activated macrophages (M2), appear to be necessary in animal models for the progression from myocarditis to DCM.