CHAPTER 63: MYOCARDITIS

INTRODUCTION

The term myocarditis describes the presence of inflammatory cells in the myocardium and implies that the presenting clinical phenotype is attributable to myocardial inflammation. Therefore, myocarditis is diagnosed when myocardial inflammation is proven and there are clinical manifestations that can be causally linked to the inflammatory substrate. The descriptive diagnosis of myocarditis encompasses a wide spectrum of etiologically different diseases that share, as unique criterion, the presence of myocardial inflammation.

In the 1980s, the World Health Organization and the International Society and Federation of Cardiology defined myocarditis as an inflammatory disease of the myocardium wherein the diagnosis is established by histologic, immunologic, and immunohistochemical criteria. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized.² Whereas the Dallas criteria¹ insisted on the demonstration of mononuclear cellular infiltration accompanying a demonstrable and ongoing myocyte damage, the definition of myocarditis recently updated by the European Society of Cardiology (ESC) working group on myocardial and pericardial diseases requires the presence of ≥ 14 lymphocytes/mm² including CD3-positive T lymphocytes ≥ 7 cells/mm² but no more than 4 monocytes/mm².³ These descriptive definitions did not include etiologic basis of myocardial involvement and clinical information.

Myocarditis can be infectious or noninfectious in origin, and the latter includes autoimmune/immune-mediated, hypersensitivity, or toxic causes. Infective myocarditis is induced by myocardiotrophic viruses such as Coxsackie B virus or endotheliotropic parvovirus B19 followed by interstitial inflammatory cell infiltration and myocardial tissue damage manifesting clinically with symptoms, circulating biomarker abnormalities, and imaging-verified myocardial alterations. The clinical presentation is “fulminant,” acute or chronic illness.³ The diagnosis is either pathologically proven or considered suspect; only pathology-based evidence is accepted as a definitive diagnosis of myocarditis,⁴ and surrogate terms such as clinically suspected myocarditis cannot be equated with the diagnostic certainty of histologically verified disease. Development of molecular imaging strategies targeting the presence of myocardial inflammation is not beyond the realm of possibility.⁵

At present, endomyocardial biopsy (EMB) remains the unique tool for the diagnosis in vivo; surgical samples can be equally informative, such as the left ventricular (LV) apex resected during ventricular assist device implantation. Reasons for not performing EMB are numerous. EMB is an invasive procedure and is associated with not negligible complications, such as ventricular wall perforation, pericardial effusion, and tamponade. Although this reason is repeatedly cited as the major limitation, EMBs are routinely and frequently performed to monitor allogeneic reaction and opportunistic infections in transplanted patients and have been reported safe both in adults⁴ and children.⁶ The major reasons why clinical utilization of EMB is discouraged include (1) the lack of evidence-based effective treatment for myocarditis; (2) the nonuniform and non–universally agreed upon diagnostic criteria; and (3) the interobserver variability among pathologists interpreting the same biopsy samples. The reports of limitations of Dallas criteria– based interpretation⁷ and the results of the National Institutes of Health Myocarditis Trial⁸ have effectively changed ...