Heart Health
Olivia C. Welter, PharmD
In its June 2024 issue, the Journal of the American College of Cardiology published a multi-society guideline for the management of hypertrophic cardiomyopathy (HCM). It builds upon a 2020 guideline, offering clinicians several revisions and new recommendations to consider, including guidance about a new class of medication, genetic factors to take into account for patients, and contraindications for treatment.
Cardiac myosin inhibitors
A new class of medication, cardiac myosin inhibitors, first entered the market in April 2022 when FDA approved mavacamten.
Drugs such as mavacamten work to reduce the interaction between actin and myosin, which in turn, lessens squeezing and minimizes stress on the heart. Although not mentioned by name in the updated guidelines, aficamten is another cardiac myosin inhibitor FDA is investigating. The agency has granted aficamten a breakthrough therapy designation, meaning the development and review of the drug will be expedited.
According to the guideline, cardiac myosin inhibitors are good options for patients who have symptomatic obstructive HCM, but they should only be prescribed to adult patients.
Pharmacologic treatment steps
Pharmacologic treatment for HCM is mainly used for symptomatic relief, as there is a lack of data demonstrating that any medication alters the natural history of the condition. Authors of the new guideline have not revised the recommendations for the first two steps in treating symptomatic obstructive HCM. The first-line therapy is still a nonvasodilating b-blocker titrated to effectiveness or to the maximally tolerated dose. In the guideline, authors said that clinicians should not declare b-blocker failure until physiologic evidence, such as suppressed resting heart rate, demonstrates b-blockade.
In cases where a b-blocker fails and does not relieve symptoms adequately, the next step is for clinicians to move onto a nondihydropyridine calcium channel blocker, such as verapamil or diltiazem.
According to the revised third step of the update, clinicians can consider escalating therapy if symptoms continue and adding a cardiac myosin inhibitor or disopyramide. However, a risk evaluation and mitigation strategy is required for mavacamten use due to a documented decrease in left ventricular ejection fraction (LVEF) to less than 50% in up to 10% of patients. If the prescriber selects disopyramide as a therapy, it should be used in combination with a medication with atrioventricular nodal blocking properties, like a b-blocker, verapamil, or diltiazem, according to the guideline.
Clinicians can consider septal reduction therapy (SRT) instead of mavacamten or disopyramide. SRT is a surgical procedure which should be performed in a comprehensive HCM center.
HCM genetics
HCM is a genetic heart muscle disease that can be passed down from a parent to their child. Because of this, genetic testing is common for patients with HCM and their family members. According to the guideline, 30% to 60% of patients with HCM have a pathogenic cardiac sarcomere genetic variant. For such patients, especially those under 45 years old, authors of the updated guideline suggest that valsartan may be a beneficial agent to use for slowing adverse cardiac remodeling. The clinical trial referenced in the guideline included patients as young as age 8 years, indicating that valsartan can be considered for eligible pediatric patients as well.
Contraindications
The updated guideline includes several new recommendations for contraindications of medications, particularly cardiac myosin inhibitors. If a patient taking a cardiac myosin inhibitor develops persistent systolic dysfunction defined as LVEF less than 50%, then clinicians should discontinue the medication. Clinicians can also reasonably consider discontinuing verapamil, diltiazem, or disopyramide for these patients.
Cardiac myosin inhibitors are contraindicated in patients who are pregnant due to potential teratogenic effects of the medication. However, this recommendation is based on findings from non-human studies.
Guideline experts suggest that clinicians use caution when introducing pharmacologic therapies to patients who are being treated for coexisting conditions, as some medications can cause or worsen their symptoms of obstructive HCM. Positive ionotropic agents, pure vasodilators, and high-dose diuretics are generally contraindicated in patients with obstructive HCM because of the potential for symptomatic issues. ■