Hypertrophic cardiomyopathy: investigational drugs inhibiting myosin and upcoming agents

ABSTRACT

Introduction

Hypertrophic cardiomyopathy (HCM), a phenotypically variable disorder with a genetic basis, was first described in the late 1800s. Since the discovery of the disease, various medical and surgical treatments have been proposed with surgical treatments proving to be of more benefit than medical in patients with severe symptoms. Although beta blockers, calcium channel blockers, and disopyramide have been used for their negative inotropic effect, the data behind utilization of these medications is weak at best.

Areas covered

Herein, we describe a first-in-man class of medications called cardiac myosin inhibitors (CMI), which have been recently approved by the Food and Drug Administration (FDA) for the treatment of symptomatic patients with obstructive HCM. PubMed was the primary database searched.

Expert opinion

Whether these medications will stand the test of time remains to be seen. They do appear to provide significant benefit and disease modification in early randomized trials with the drawback of decreasing contractility and ejection fraction. In our opinion, this new class of medications is an option for patients with NYHA class II-III symptoms from obstructive HCM who have EF ≥ 55%.

KEYWORDS:

• Hypertrophic obstructive cardiomyopathy
• mavacamten
• cardiac myosin inhibitors
• CMI
• hypertrophic cardiomyopathy

Article highlights

• Hypertrophic cardiomyopathy is a genetically mediated disease that leads to dynamic LVOT obstruction and significant symptoms in approximately 1 in 200 people.

• Typical medical treatments in the past have included beta blockers, calcium channel blockers, and disopyramide.

• In medicine refractory disease, septal reduction therapy, whether by alcohol septal ablation or myectomy, has been utilized for symptomatic management.

• However, surgical management should only be performed at experienced centers given the complexity of the surgery.

• Cardiac myosin inhibitors are first in class medicines that target the pathophysiology of HCM by preventing myosin-actin crossbridges from forming and thus decreasing contractility.

• Although, this class of medications certainly needs further study, it could be a paradigm shift in medical treatment of obstructive HCM.

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 received an honorarium from Expert Review of Proteomics for their review work but have no other relevant financial relationships to disclose.

Additional information

Funding

This paper was not funded.