Am J Ther. 2026 Oct 15. doi: 10.1097/MJT.0000000000002245. Online ahead of print.
ABSTRACT
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disorder associated with morbidity. Rapid advances in therapeutics-particularly the emergence of cardiac myosin inhibitors (CMIs)-suggest that current management guidelines are lagging best practices.
AREAS OF UNCERTAINTY: Cardiac myosin inhibitors have revolutionized the management of patients with obstructive HCM. Patients with nonobstructive HCM have had limited therapeutic options historically; however, the recently published ACACIA-HCM trial demonstrated significant benefit in these patients and may represent a new treatment option in these patients, although more long-term data and research are needed in this population.
DATA SOURCES: A literature review was performed using PubMed/MEDLINE, Google Scholar, society guidelines, and recently published clinical trials evaluating HCM, cardiac myosin inhibitors, beta blockers, calcium channel blockers, septal reduction therapy, and emerging therapies for obstructive and nonobstructive HCM.
THERAPEUTIC ADVANCES: Historically, HCM management has centered on negative inotropic/chronotropic agents to alleviate left ventricular outflow tract obstruction by decreasing the force of contraction and increasing diastolic filling time. The introduction of CMIs represents a paradigm shift by directly targeting the underlying hypercontractility, representing the first therapy specifically designed to treat obstructive HCM, obviating the need for earlier agents, which had limited data and at best modest therapeutic benefit. There may finally be an available treatment for diastolic heart failure in patients with nonobstructive HCM with myosin inhibition, as results from a recent trial ACACIA-HCM were favorable. Furthermore, ongoing investigations are exploring novel approaches such as metabolic modulators.
CONCLUSIONS: The management of HCM is undergoing substantial transformation, yet guideline recommendations continue to prioritize beta blockers as first-line therapy despite mounting evidence supporting CMIs. Although treatment strategies for obstructive HCM have evolved significantly, optimal approaches for nonobstructive disease remain unclear. Addressing this gap represents a critical priority for future research.
PMID:42875832 | DOI:10.1097/MJT.0000000000002245