Promising therapies for adults with symptomatic obstructive hypertrophic cardiomyopathy: 2023 and beyond

ABSTRACT

Introduction

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart disease with an estimated prevalence in the general population of 0.2% to 0.6%. Clinically, HCM can range from no symptoms to severe symptoms such as heart failure or sudden cardiac death. Currently, the management of HCM involves lifestyle modifications, familial screening, genetic counseling, pharmacotherapy to manage symptoms, sudden cardiac death risk assessment, septal reduction therapy, and heart transplantation for specific patients. Multicenter randomized controlled trials have only recently explored the potential of cardiac myosin inhibitors (CMIs) such as mavacamten as a directed pharmacological approach for managing HCM.

Areas covered

We will assess the existing medical treatments for HCM: beta-blockers, calcium channel blockers, disopyramide, and different CMIs. We will also discuss future HCM pharmacotherapy guidelines and underline this patient population’s unfulfilled needs.

Expert opinion

Mavacamten is the first-in-class CMI approved by the FDA to target HCM pathophysiology specifically. Mavacamten should be incorporated into the standard therapy for oHCM in case of symptom persistence despite using maximally tolerated beta blockers and/or calcium channel blockers. Potential drug-drug interactions should be assessed before initiating this drug. More studies are needed on the use of CMIs in patients with kidney and/or liver failure and pregnant/breastfeeding patients.

KEYWORDS:

• Hypertrophic cardiomyopathy
• pharmacotherapy
• cardiac myosin inhibitor
• medical management
• septal reduction therapy

Article highlights

• Until recently, there was no available targeted medical treatment for HCM, with beta-blockers and calcium channel blockers being the basis of therapy.

• Despite being almost curative for oHCM patients, SRT is not readily available for this patient population due to a lack of experienced HCM centers.

• Mavacamten is the first FDA-approved CMI specifically targeting the pathophysiology of HCM. Across all its clinical trials, it has shown a significant reduction in SRT eligibility compared to placebo.

• Other targeted therapies such as aficamten and gene therapy are still in various development and testing stages.

• Mavacamten should be integrated into the treatment regimen of oHCM patients who have persistent symptoms despite standard medical therapy.

Declaration of interest

M Desai is a consultant with research agreements with Bristol Myers Squibb, Cytokinetics, Tenaya, Viz-AI, and Edgewise.

A Gaballa and S Jadam have received salary support from unrestricted philanthropic gifts from the Haslam family, Ratner family, Stinson family, and Anderson family. No industry support was utilized in the conduct of this study.

The authors have no other 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 apart from those disclosed

Acknowledgments

M Desai acknowledges the Haslam family endowed chair in cardiovascular medicine.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.