Myocarditis: causes, mechanisms, and evolving therapies

ABSTRACT

Introduction

Myocarditis is a severe lymphocyte-mediated inflammatory disorder of the heart, mostly caused by viruses and immune checkpoint inhibitors (ICIs). Recently, myocarditis as a rare adverse event of mRNA vaccines for SARS-CoV-2 has caused global attention. The clinical consequences of myocarditis can be very severe, but specific treatment options are lacking or not yet clinically proven.

Areas covered

This paper offers a brief overview of the biology of viruses that frequently cause myocarditis, focusing on mechanisms important for viral entry and replication following host infection. Current and new potential therapeutic targets/strategies especially for viral myocarditis are reviewed systematically. In particular, the immune system in myocarditis is dissected with respect to infective viral and non-infective, ICI-induced myocarditis.

Expert opinion

Vaccination is an excellent emerging preventative strategy for viral myocarditis, but most vaccines still require further development. Anti-viral treatments that inhibit viral replication need to be considered following viral infection in host myocardium, as lower viral load reduces inflammation severity. Understanding how the immune system continues to damage the heart even after viral clearance will define novel therapeutic targets/strategies. We propose that viral myocarditis can be best treated using a combination of antiviral agents and immunotherapies that control cytotoxic T cell activity.

KEYWORDS:

• Myocarditis
• virus
• vaccine
• immune checkpoint inhibitors
• mRNA vaccines
• immunotherapy

Article highlights

• Myocarditis is a serious inflammatory disease of the heart affecting all age groups and can present as acute, fulminant, subacute, and chronic forms.

• According to immune cell infiltrates, myocarditis is classified as lymphocytic myocarditis, eosinophilic myocarditis, giant cell myocarditis, and granulomatous myocarditis.

• Viruses are most common etiological agents in myocarditis, and they promote cardiac damage directly and/or indirectly via inflammatory responses.

• Vaccines are the most effective way to avoid viral myocarditis.

• Anti-viral and/or immunomodulatory therapies are considered to be effective in reducing viral load and myocardial inflammation.

• Novel preventive and interventional therapeutic strategies to minimize viral infections and myocardial inflammation will effectively prevent further damage to the heart and will preserve left ventricular function.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.