# Hypertrophic Cardiomyopathy and Phenocopies: New Therapies for Old Diseases—Current Evidence and Future Perspectives

## TL;DR

This paper reviews new treatments for hypertrophic cardiomyopathy and related conditions, focusing on recent advances in disease-modifying therapies.

## Contribution

The paper provides an updated overview of current and emerging therapies for HCM and its phenocopies, emphasizing recent clinical developments.

## Key findings

- New therapies like cardiac myosin inhibitors and gene silencers are transforming treatment for HCM and amyloidosis.
- Enzyme replacement and oral chaperone therapies are now available for Anderson–Fabry disease.
- Multi-organ and multimodal diagnostic approaches are crucial for accurate diagnosis and treatment selection.

## Abstract

The hypertrophic cardiomyopathy (HCM) clinical phenotype includes sarcomeric HCM, which is the most common form of inherited cardiomyopathy with a population prevalence of 1:500, and phenocopies such as cardiac amyloidosis and Anderson–Fabry disease, which are considered rare diseases. Identification of cardiac and non-cardiac red flags in the context of multi-organ syndrome, multimodality imaging, including echocardiography, cardiac magnetic resonance, and genetic testing, has a central role in the diagnostic pathway. Identifying the specific disease underlying the hypertrophic phenotype is very important since many disease-modifying therapies are currently available, and phase 3 trials for new treatments have been completed or are ongoing. In particular, many chemotherapy agents (alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting clonal cells) allowing one to treat AL amyloidosis, transthyretin stabilizers (tafamidis and acoramidis), and gene silencers (patisiran and vutrisiran) are available in transthyretin cardiac amyloidosis, and enzyme replacement therapies (agalsidase-alpha, agalsidase-beta, and pegunigalsidase-alpha) or oral chaperone therapy (migalastat) can be used in Anderson–Fabry disease. In addition, the introduction of cardiac myosin inhibitors (mavacamten and aficamten) has deeply modified the treatment of hypertrophic obstructive cardiomyopathy. The aim of this review is to describe the new disease-modifying treatments available in HCM and phenocopies in light of current scientific evidence.