An evaluation of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy in adults

ABSTRACT

Introduction

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder leading to hypertrophy of the left ventricle excluding other etiologies. Patients can experience exertional chest pain, dyspnea, syncope or even sudden cardiac death (SCD). Traditional medical management consists of beta blockers (BB), nondihydropyridine calcium channel blockers and disopyramide. Mavacamten, a novel cardiac myosin inhibitor, has recently been shown to improve both quantitative and qualitative measures of obstructive HCM allowing some patients to defer septal reduction therapy.

Areas covered

This review delves into the pharmacotherapy of mavacamten, the evidence behind this first-in-class drug for HCM, guidance for clinical usage, and possible future uses for cardiac myosin inhibitors.

Expert opinion

Mavacamten should be incorporated into the standard armamentarium of medications used to treat obstructive HCM. PIONEER-HCM, EXPLORER-HCM and VALOR-HCM demonstrated improvements in peak LVOT gradient both at rest and post-exercise, cardiac biomarkers, New York Heart Association (NYHA) functional class and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Unlike other medications utilized for treatment, mavacamten can delay or even obviate the need for septal reduction therapy.

KEYWORDS:

• Mavacamten
• hypertrophic cardiomyopathy
• septal reduction therapy
• EXPLORER HCM
• VALOR HCM

Article highlights

• Hypertrophic cardiomyopathy is characterized by hypercontractility in the setting of increased left ventricular hypertrophy due to abnormalities in cardiac sarcomeres.

• Mavacamten is a first-in-class cardiac myosin inhibitor that decreases actin-myosin bridge formation and leads to decreased left ventricular outflow obstruction in obstructive hypertrophic cardiomyopathy.

• Mavacamten should be part of the standard treatment therapy for obstructive hypertrophic cardiomyopathy after initial uptitration of beta blockade and/or calcium channel blockade to maximally tolerated dosages.

• As evidenced by the VALOR HCM trial, mavacamten can be utilized in patients who are candidates for septal reduction therapies. In obstructive hypertrophic cardiomyopathy patients, mavacamten was shown to decrease the eligibility for invasive management.

• In substudy of VALOR HCM, mavacamten was also shown to improve diastology in both the treatment group compared to the placebo group.

• Currently, aficamten, another cardiac myosin inhibitor, is being investigated with promising phase 2 trial results for obstructive hypertrophic cardiomyopathy patients.

Acknowledgments

Dr Desai acknowledges the Haslam Family endowed chair in CV medicine.

Declaration of interests

M Desai is a consultant for BMS, Medtronic and cytokinetics. SE Nissen and N Desai receive research support from BMS. 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.