Therapeutic Targets for Myocardial Fibrosis: A Comprehensive Review of Current and Emerging Approaches

INTRODUCTION: Cardiovascular disorders (CVDs) remain the leading cause of global mortality, surpassing other chronic illnesses. An alarming rise in CVD-related deaths, particularly among younger populations, has intensified research efforts to better understand the disease and its complications. Among these, myocardial fibrosis plays a central role in the development of cardiac dysfunction and heart failure. Given its multifactorial nature, diverse therapeutic strategies are required to manage its progression effectively. METHODS: A comprehensive literature review was conducted using databases such as PubMed, Scopus, Elsevier, and ClinicalTrials.gov. Only peer-reviewed, English-language studies focusing on molecular mechanisms and therapeutic strategies for myocardial fibrosis were included. Irrelevant, non-English, and non-peer-reviewed sources were excluded. Data from selected preclinical and clinical investigations were qualitatively synthesized. RESULTS: Myocardial fibrosis arises from various pathological conditions, including ischemia, hyperlipidemia, and genetic disorders, which promote maladaptive cardiac remodeling. Although traditional treatments such as RAAS inhibitors and β-blockers offer symptomatic relief, they do not halt disease progression. Recent evidence suggests that multiple molecular pathways are involved in the development of fibrosis, opening opportunities to explore alternative therapeutic targets. DISCUSSION: Due to its complex pathophysiology, myocardial fibrosis cannot be addressed by monotherapy alone. Anti-TGF-β agents have emerged as promising candidates, alongside newer therapies like SGLT2 inhibitors and MMP inhibitors. Additionally, regenerative approaches, such as stem cell and gene therapy, offer future avenues, though technical and safety challenges accompany them. CONCLUSION: Myocardial fibrosis remains a critical contributor to heart failure, and current treatments are insufficient to reverse its course. A multifaceted therapeutic approach targeting different molecular mechanisms holds the key to improved clinical outcomes. Continued translational research is crucial for advancing emerging therapies from bench to bedside.