# Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives

## TL;DR

This review discusses the molecular causes of arrhythmogenic cardiomyopathy and explores new therapies that could modify the disease.

## Contribution

The paper provides a comprehensive summary of molecular pathways and emerging targeted therapies for ACM.

## Key findings

- ACM is linked to genetic mutations causing structural and electrical heart anomalies.
- Animal models and stem cells are advancing understanding of ACM's molecular pathogenesis.
- Current treatments are palliative, but new therapies aim to modify the disease itself.

## Abstract

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac disease characterized by a progressive loss of cardiomyocytes associated with fibrofatty myocardial replacement, resulting in a heightened risk of ventricular arrhythmias and sudden cardiac death. ACM is a common cause of sudden death in young individuals, and exercise has been proven to be a factor in disease progression. Current therapeutic strategies, including lifestyle modification, antiarrhythmic pharmacological therapy, catheter ablation, and the placement of implantable cardioverter-defibrillators, remain primarily palliative options rather than addressing the underlying molecular substrate. The pathogenesis of ACM includes complex molecular and cellular mechanisms, linking genetic mutations to structural and electrical anomalies of the ventricle. The lack of targeted therapies contributes to a challenging approach to the disease. It highlights the need for a better understanding of the mechanisms that lead to myocardial remodeling and arrhythmic predisposition. With the help of animal models (especially murine) and induced pluripotent stem cells, there have been advances in understanding the molecular pathogenesis of ACM. In this review, we summarized some of the pathogenic molecular pathways involved in the development of ACM and emerging therapies targeted towards disease modification, not just prevention.