New Cardiomyopathy Guidelines Endorse Cardiac Myosin Inhibitors, Expanded Role for Exercise

Steve Ommen, MD
Credit: Mayo Clinic

New guideline recommendations from the American College of cardiology and the American Heart Association include major updates for management of hypertrophic cardiomyopathy (HCM), including a more solidified stance on the role of exercise in management of HCM and endorsing cardiac myosin inhibitors for patients with symptomatic obstructive HCM who do not get adequate symptom relief from first-line drug therapy.¹

A collaborative effort across a multitude of major organizations, the guideline was developed in collaboration and endorsed by the ACC, AHA, the American Medical Society for Sports Medicine (AMSSM), the Heart Rhythm Society (HRS), the Pediatric and Congenital Electrophysiology Society (PACES), and the Society for Cardiovascular Magnetic Resonance (SCMR).¹

“These new drugs offer an alternative for patients who have failed first-line therapy and either want to delay or possibly avoid more aggressive options,” said Steve R. Ommen, MD, medical director of the Mayo Hypertrophic Cardiomyopathy Clinic and chair of the guideline writing committee.² “With this guideline, we’re providing clinicians with point-of-care guidance about effectively using this first-in-class, evidence-based treatment option and improving their patients' quality of life.”

Published on May 08, 2024 in the Journal of the American College of Cardiology and Circulation, the 82-page document was composed by Ommen and 23 other members of the guideline writing committee with the intent of encapsulating the wealth of information related to management and pathophysiology related to HCM since the last guideline release in 2020. The press release announcing the publication highlights the importance of collaborative decision-making and new updates surrounding exercise and the use of cardiac myosin inhibitors as key highlights of the document.¹

Citing more than 400 references, the document greets readers with a 1-page synopsis of 5 new and 5 substantially revised recommendations included in the 2024 guideline updates.¹

New recommendations:¹

• Exercise stress testing is recommended to determine functional capacity and to provide prognostic information in pediatric patients with HCM, regardless of symptom status. (Class 1)
• Valsartan may be beneficial to slow adverse cardiac remodeling among patients with Nonobstructive HCM due to a pathogenic or likely pathogenic cardiac sarcomere genetic variant and a mild phenotype. (Class 2B)
• Cardiac myosin inhibitors should be discontinued in patients with HCM who develop persistent systolic dysfunction. (Class 1)
• Universal restriction from vigorous physical activity or competitive sports is not indicated for most patients with HCM. (Class 3: No Benefit)
• Use of mavacamten is contraindicated due to potential teratogenic effects in pregnant women (Class 3: Harm)

Substantially revised recommendations:¹

• Extended ambulatory monitoring is recommended to screen for atrial fibrillation as part of initial evaluation and annual follow-up in with HCM who are deemed to be at high risk for developing atrial fibrillation based on the presence of risk factors or as determined by a validated risk score, and who are eligible for anticoagulation. (Class 1)
• ·Discussion of the estimated 5-year sudden death risk and mortality rates can be useful during the shared decision-making process for ICD placement among patients withHCM with 1 or more major sudden cardiac death risk factors. (Class 2A)
• Adding a myosin inhibitor (adult patients only), or disopyramide (in combination with an atrioventricular nodal blocking agent), or SRT performed at experienced centers, is recommended in patients with obstructive HCM who have persistent symptoms attributable to LVOTO despite beta blockers or nondihydropyridine calcium channel blockers. (Class 1)
• Participation in vigorous recreational activities is reasonable after an annual comprehensive evaluation and shared decision-making with an expert professional who balances potential benefits and risks for patients with HCM (Class 2A)
• participation in competitive sports may be considered after review by an expert provider with experience managing athletes with HCM who conducts an annual comprehensive evaluation and shared decision-making that balances potential benefits and risks. (Class 2B)

At the time of publishing, mavacamten (Camzyos) is the only cardiac myosin inhibitor with FDA approval for use in patients with obstructive HCM. Mavacamten received initial approval from the FDA in April 2022 for improving functional capacity and symptoms in patients with symptomatic obstructive based on data from the EXPLORER-HCM trial.³

In June 2023, a subsequent approval for an updated label would expand the agent’s indication to include data from the VALOR-HCM study in the prescribing information, which will now reflect the effects of the agent on need and eligibility for septal reduction therapy in patients with obstructive HCM. Although mavacamten is the only approved cardiac myosin inhibitor, much of the excitement surrounding the class extends to aficamten—a next generation cardiac myosin inhibitor from Cytokinetics, which has shown promise in its own clinical program, including the phase 3 SEQUOIA-HCM trial.^4,5

“Incorporating the most recent data, this new guideline equips clinicians with the latest recommendations for the treatment of HCM,” Ommen added.¹ “We’re seeing more evidence that patients with HCM can return to their normal daily lives with proper care and management.”

References:

1. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/hrs/paces/SCMR guideline for the management of hypertrophic cardiomyopathy. Journal of the American College of Cardiology. Published online May 8, 2024. doi:10.1016/j.jacc.2024.02.014
2. American Heart Association. "Exercise, new drug class recommended for management of hypertrophic cardiomyopathy." Newsroom. Heart.org, May 08, 2024. Available from: https://newsroom.heart.org/news/exercise-new-drug-class-recommended-for-management-of-hypertrophic-cardiomyopathy. Accessed May 09, 2024.
3. HCPLive. "FDA approves mavacamten for obstructive hypertrophic cardiomyopathy." HCPLive, April 28, 2022. Available from: https://www.hcplive.com/view/fda-approves-mavacamten-for-obstructive-hypertrophic-cardiomyopathy. Accessed May 09, 2024.
4. HCPLive. "FDA approves updated label for mavacamten in obstructive hypertrophic cardiomyopathy." HCPLive, June 15, 2023. Available from: https://www.hcplive.com/view/fda-approves-updated-label-for-mavacamten-in-obstructive-hypertrophic-cardiomyopathy. Accessed May 09, 2024.
5. HCPLive. "Cytokinetics announces positive topline data for aficamten in Sequoia HCM." HCPLive, December 27, 2024. Available from: https://www.hcplive.com/view/cytokinetics-announces-positive-topline-data-for-aficamten-in-sequoia-hcm. Accessed May 09, 2024.