New HCM Guidelines Focus on Cardiac Myosin Inhibitors and Exercise

The American Heart Association (AHA) and the American College of Cardiology (ACC), with the support of several other professional societies, have released updated guidelines for the management of patients with hypertrophic cardiomyopathy (HCM).

Combining the latest evidence and emphasizing collaborative decision-making, the document contains updated recommendations on cardiac myosin inhibitors, physical activity, and risk stratification for sudden cardiac death, with a separate section for pediatric patients.

Steve R. Ommen, MD (Mayo Clinic, Rochester, MN), chair of the AHA/ACC writing committee, told TCTMD the update is the first to use a new process in which a complete guideline rewrite is not required and, instead, only sections with new data are revised. What prompted this latest edition was the US Food and Drug Administration’s April 2022 approval of mavacamten (Camzyos; Bristol Myers Squibb) for the treatment of symptomatic obstructive HCM, he said.

“I hope these guidelines refine the place in therapy for cardiac myosin inhibitors as it stands today and encourages patients with hypertrophic cardiomyopathy to lead active healthy lifestyles,” Ommen said.

The guideline, published online Wednesday in both Circulation and the Journal of the American College of Cardiology, was developed in collaboration with and endorsed by the American Medical Society for Sports Medicine, the Heart Rhythm Society, the Pediatric & Congenital Electrophysiology Society, and the Society for Cardiovascular Magnetic Resonance.

Mavacamten Now Included

The document gives a class 1 recommendation for use of cardiac myosin inhibitors in patients with symptomatic obstructive HCM who are not responding to or tolerating first-line therapies.

Ommen said he’s seen mavacamten “used quite a bit” since it was approved but noted that its uptake varies by institution. “In places that don't have surgeons or interventional cardiologists to deliver the invasive therapies,” he said, “they now have an option to offer patients that they can prescribe for them right there in the practice.”

It’s not, however, a good option for all patients, he indicated. “In reality, about a third of patients don't get symptomatic improvement from mavacamten. So it's not like it's totally eliminating the need for those other procedures, and many patients don't want to take a medication lifelong when they can have an option that's a fix for an anatomic problem that might be a one-and-done solution.”

Ommen also pointed out that the risk evaluation and mitigation strategy (REMS) program needed for prescription of mavacamten, which requires frequent echocardiographic assessment, is a turnoff for many. “There's a lot of logistics scheduling for surveillance to make sure that there's no adverse effects from the drug; that decreases some patients’ and some providers’ enthusiasm for using it,” Ommen said, adding that he still expects the updated guidelines to increase its use nationally.

Clarifications on Exercise

Another major addition in the guidelines is an “evolution” in the way physical activity should be approached for HCM patients. Previously, the recommendation was for exercise of only low-to-moderate intensity.

“We now have recognized that it's reasonable for most patients to even perform ‘vigorous’ activity, which is defined by at least an hour of activity beyond the level of 6 METS, which is jogging at a brisk pace, per week,” Ommen explained, noting that this was given a class 2a recommendation. “So it's not like vigorous like big-time athletes. It's vigorous compared to what we hope all people who are trying to improve their health and activity would be doing as part of a healthy lifestyle.”

That said, recommendations for exercise at the competitive athletic level were untouched. “It's still a class 2b because we just feel like the intensity of training, competition environments, etc, haven't been addressed in published literature,” he said, adding that this issue doesn’t regularly come up in clinical practice as much as it does in debates at national meetings. “The important thing is that we can now reliably tell most patients, particularly if they have no symptoms, that you should be getting the same level of exercise everyone else is supposed to.”

Other Additions

Pediatric patients now have a special section in the HCM guidelines as some new risk-prediction tools have emerged in recent years for this population. But this differentiation was also partially logistical, according to Ommen.

“More because of document standards and rubrics, we separated it out from the adults altogether, and we just needed more words to describe the differences,” he explained. “By making the children a separate category in the document, it looks like it's new. It was all there before, other than these new tools and risk markers. So it's now a little bit more stand-alone than it was for adults, which might bring it to more attention to practicing pediatric cardiologists.”

Additionally, Ommen pointed out an important change with a class 1 recommendation for more intensive, extended monitoring for subclinical atrial fibrillation. “There's a risk assessment goal for patients that have higher risk of A-fib,” he said. “Monitoring them with an ambulatory ECG more frequently to make sure that we're not leaving them unprotected for risk of stroke is the goal of that recommendation.”

Perhaps the biggest open question in this field is related to the treatment of symptomatic nonobstructive HCM, Ommen said. “There are a bunch of trials ongoing looking into that, but we don't have data yet to publish in the guideline document.”

Also, he said he’d like to see more research into the mechanisms underlying the effects of cardiac myosin inhibitors. “It remains unknown whether the fact that they target a cellular mechanism unique to hypertrophic cardiomyopathy has any implications long term other than relief of obstruction (ie, other disease-modifying principles of this beyond relief of outflow tract obstruction) or are they just a simple and novel way to achieve relief of outflow tract obstruction.”

Lastly, Ommen said, there remains a need for further refinement of risk-prediction models in HCM. He expects that ongoing clinical trials in these areas will enable another guideline update within the “next few years.”