# Inflammasomes as Potential Therapeutic Targets to Prevent Chronic Active Viral Myocarditis—Translating Basic Science into Clinical Practice

## TL;DR

This paper explores how inflammasomes, which are part of the immune system, can both protect against and worsen viral myocarditis, suggesting new therapies to prevent chronic heart damage.

## Contribution

The paper highlights inflammasomes as potential therapeutic targets and reviews emerging strategies to balance immune response and prevent chronic myocarditis.

## Key findings

- Inflammasomes are crucial for fighting viral infections but can cause chronic heart damage if overactivated.
- Therapies targeting inflammasome pathways, like IL-1 receptor blockers and NLRP3 inhibitors, may prevent progression to chronic myocarditis.
- Early identification of at-risk patients could improve outcomes by balancing immune response and limiting cardiac injury.

## Abstract

Despite substantial progress in medical care, acute myocarditis remains a life-threatening disorder with a sudden onset, often unexpectedly complicating a simple and common upper respiratory tract infection. In most cases, myocarditis is triggered by viral infections (over 80%), with an estimated incidence of 10–106 per 100,000 annually. The clinical course may worsen in cases of mixed etiology, where a primary viral infection is complicated by secondary bacterial pathogens, leading to prolonged inflammation and an increased risk of progression to chronic active myocarditis or dilated cardiomyopathy. We present a case report illustrating the clinical problem of acute myocarditis progression into a chronic active form. A central element of host defense is the inflammasome—an intracellular complex that activates pyroptosis and cytokine release (IL-1β, IL-18). While these processes help combat pathogens, their persistent activation may sustain inflammation and trigger heart failure and cardiac fibrosis, eventually leading to dilated cardiomyopathy. In this review, we summarize the current understanding of inflammasome pathways and their dual clinical role in myocarditis: they are essential for controlling acute infection but may become harmful when overactivated, contributing to chronic myocardial injury. Additionally, we discuss both novel and established therapeutic strategies targeting inflammatory and anti-fibrotic mechanisms, including IL-1 receptor blockers (anakinra, canakinumab), NOD-like receptor protein 3 (NLRP3) inhibitors (colchicine, MCC950, dapansutrile, INF200), NF-κB inhibitors, and angiotensin receptor-neprilysin inhibitors (ARNI), as well as microRNAs. Our aim is to emphasize the clinical importance of early identification of patients at risk of transitioning from acute to chronic inflammation, elucidate the role of inflammasomes, and present emerging therapies that may improve outcomes by balancing effective pathogen clearance with limitation of chronic cardiac damage.