Cardio-Immunology of Myocarditis: Focus on Immune Mechanisms and Treatment Options

Abstract

Myocarditis and inflammatory cardiomyopathy are syndromes, not aetiological disease entities. From animal models of cardiac inflammation we have detailed insight of the strain specific immune reactions based on the genetic background of the animal and the infectiosity of the virus. Innate and adaptive immunity also react in man. An aetiological diagnosis of a viral vs. a non-viral cause is possible by endomyocardial biopsy with histology, immunohistology and PCR for microbial agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy on the basis of the genetic background and the predisposition for inflammation. It analyses the epidemiologic shift in cardiotropic viral agents in the last 30 years. Based on the understanding of the interaction between infection and the players of the innate and adaptive immune system it summarizes pathogenetic phases and clinical faces of myocarditis. It gives an up-to-date information on specific treatment options beyond symptomatic heart failure and antiarrhythmic therapy. Although inflammation can resolve spontaneously, specific treatment directed to the causative etiology is often required. For fulminant, acute, and chronic autoreactive myocarditis without viral persistence immunosuppressive treatment can be life-saving, for viral inflammatory cardiomyopathy ivIg treatment can resolve inflammation and often eradicate the virus.

Keywords: PCR of cardiotropic viruses; endomyocardial biopsy; immunohistology; immunopathogenesis; immunosuppressive therapy; ivIg; myocarditis.

Figure 1

Immune system and cytokine pattern in various susceptical and resistant mouse myocarditis models [Balbc, A/J mice, after CVB3 infection with a consecutive autoimmune reaction to cardiac myosi (25)].

Figure 2

Sequence of events in myocardial inflammation.

Figure 3

A selection of circulating anticardiac antibodies [from Maisch and Pankuweit (9) with permission from Springer-Nature].

Figure 4

Viral infection, antigen presentation, response by the adaptive immune system [inserted images from Maisch and Pankuweit (9) with permission from Springer-Nature]. AMLA, antimyolemmal antibodies(ab); ASA, antisarcolemmal ab; AFA, antifibrillary ab; AIDA, antiintercalated disk ab(fig.); BAR, betarecepator ab; ANA, antinuclear ab.

Figure 5

Histological phenotypes and components of myocarditis and inflammatory cardiomyopathy can correlate with clinical manifestations (faces).

Figure 6

(A) Epidemiological shift in the Myocarditis Registry from entero-(green line) and adenoviruses (brown line) to Parvovirus B 19 (dark blue line) in the late 1980-ties. The number of patients with nonviral myocarditis (light blue line) varied from 50 to 80% in the same time span. (B) PCR-based etiology of viral and autoreactive myocarditis and dilated cardiomyopathy without inflammation (4th column) [modified from Pankuweit et al. (60)]. PCR-Based etiology of myocarditis and dilated cardiomyopathy. Investigation of endomyocardial biopsies from 3345 patients (1997–2003).

Figure 7

Antininflammatory action of different modes of therapy in perimyocarditis [modified from Maisch (69) with permission from Springer-Nature].

Figure 8

Etiology driven treatment in myocarditis and inflammatory cardiomyopathy [modified from Maisch (69) with permission from Springer-Nature].