Current experimental and early investigational agents for cardiac fibrosis: where are we at?

ABSTRACT

Introduction

Myocardial fibrosis (MF) is induced by factors activating pro-fibrotic pathways such as acute and prolonged inflammation, myocardial ischemic events, hypertension, aging process, and genetically-linked cardiomyopathies. Dynamics and characteristics of myocardial fibrosis development are very different. The broad range of myocardial fibrosis presentations suggests the presence of multiple potential targets.

Area covered

Heart failure treatment involves medications primarily aimed at counteracting neurohormonal activation. While these drugs have demonstrated efficacy against MF, not all specifically target inflammation or fibrosis progression with some exceptions such as RAAS inhibitors. Consequently, new therapies are being developed to address this issue. This article is aimed to describe anti-fibrotic drugs currently employed in clinical practice and emerging agents that target specific pathways, supported by evidence from both preclinical and clinical studies.

Expert opinion

Despite various preclinical findings suggesting the potential utility of new drugs and molecules for treating cardiac fibrosis in animal models, there is a notable scarcity of clinical trials investigating these effects. However, the pathology of damage and repair in the heart muscle involves a complex network of interconnected inflammatory pathways and various types of immune cells. Our comprehension of the positive and negative roles played by specific immune cells and cytokines is an emerging area of research.

KEYWORDS:

• Myocardial fibrosis (MF)
• anti-fibrotic drugs
• emerging therapies
• pro-fibrotic pathways
• heart failure treatment
• neurohormonal activation
• reverse remodeling

Article highlights

• Fibrosis arises from an excessive deposition of extracellular matrix (ECM) proteins within the tissue cells.

• Traditionally, myocardial fibrosis is categorized as either ‘reparative’ or ‘reactive.’

• These two types of fibrosis patterns can co-develop within a single pathological context.

• Various purely anti-fibrotic strategies have shown promising results in preclinical models of cardiovascular disease.

• There is currently no anti-fibrotic drug that has demonstrated clear efficacy in clinical studies.

• Therapy with in vivo engineered CAR-T cells is a very promising new approach, especially in pathological conditions characterized by intense activation of pro-fibrotic pathways.

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.