Autoimmunity in Acute Myocarditis: How Immunopathogenesis Steers New Directions for Diagnosis and Treatment

Abstract

Purpose of Review Over the last decade, myocarditis has been increasingly recognized as common cause of sudden cardiac death in young adults and heart failure overall. The purpose of this review is to discuss hypothesis of development of non-infectious myocarditis, to provide a description of the immunopathogenesis and the most common mechanisms of autoimmunity in myocarditis, and to provide an update on therapeutic options. Recent Findings A new entity of myocarditis is immune checkpoint inhibitor (ICI) induced myocarditis. ICIs are used in advanced cancer to "disinhibit" the immune system and make it more aggressive in fighting cancer. This novel drug class has doubled life expectancy in metastatic melanoma and significantly increased progression free survival in advanced non-small-cell lung cancer, but comes with a risk of autoimmune diseases such as myocarditis resulting from an overly aggressive immune system. Summary Myocarditis is an inflammatory disease of the heart with major public health impact. Thorough understanding of its immunopathogenesis is crucial for accurate diagnosis and effective treatment.

Emerging role of interleukin‐13 in cardiovascular diseases: A ray of hope

“…Myocarditis refers to as localized or diffuse inflammatory lesions of the myocardium, initiated by infectious factors, most commonly, viruses and non‐infectious factors, such as systemic autoimmune disease, medications and cardiotoxins 40 . It is believed that IL‐13 consecutively contributes to regulating recruitment and differentiation of immune cells, chemokines secretion and fibrosis during the progression of myocarditis 40‐42 .…”

“…Myocarditis refers to as localized or diffuse inflammatory lesions of the myocardium, initiated by infectious factors, most commonly, viruses and non‐infectious factors, such as systemic autoimmune disease, medications and cardiotoxins 40 . It is believed that IL‐13 consecutively contributes to regulating recruitment and differentiation of immune cells, chemokines secretion and fibrosis during the progression of myocarditis 40‐42 . IL‐13 deficiency mice develop into severe myocarditis in both coxsackievirus B3 (CVB3)‐induced model and experimental autoimmune myocarditis (EAM) model, manifested in decreased systolic and diastolic left ventricular functions and decreased survival 41 .…”

“…Instead, administration with IL‐13 could significantly ameliorate the heart inflammation and cardiac injury caused by CVB3 induced myocarditis 43 . The majority of immune cells in response to myocarditis are macrophages 40 and IL‐13 targets on enhancing M2 macrophage polarization to protect the heart against myocarditis 41,43,44 . IL‐13 could decrease both T lymphocyte infiltration of the heart and activation of T lymphocytes in the spleen and influence the production of interferon (IFN)‐γ and IL‐17, which mediate the differentiation of macrophages or directly prevent from myocarditis 41,43 .…”

The Spectrum of ACS: Towards a More Personalized Approach

“…Fulminant myocarditis is defined as a myocarditis that leads within four weeks or less of symptom onset to severe heart failure, requiring medical and/or mechanical cardiovascular support. The most common etiology is viral or autoimmune in nature and, less commonly, hypersensitivity and toxic reactions to drugs [41], as well as giant cell myocarditis (a rare but very aggressive form of myocarditis often associated with autoimmune diseases).…”

Focus on Autoimmune Myocarditis in Graves' Disease: A Case-Based Review

“…Although GD is a common autoimmune thyrotoxicosis and well-known to be related to chronic heart failure (especially dilated cardiomyopathy), hyperthyroidism-associated acute myocarditis is rarely reported. However, retrospective studies reported that 9–16% of unexplained non-ischemic dilated cardiomyopathy cases have a histological evidence of myocarditis ( 9 ). Thus, there may exist huge omissions about hyperthyroidism-related myocarditis in GD patients.…”