Update on the management of HCM

Dr Carolyn Ho, Medical Director at the Cardiovascular Genetics Centre at Brigham and Women’s Hospital, Boston, US,  provided updates to the Irish Cardiac Society Annual Scientific Meeting on the management of heart muscle disease hypertrophic cardiomyopathy (HCM).

Dr Ho began her talk by outlining how mechanistic insights had changed practice and how “getting good data has driven updates to our management guidelines and the future direction we want to go in this field”.

She said HCM is clinically diagnosed as having unexplained left ventricular hypertrophy (LVH) and outlined how the natural history of HCM has been extremely variable, which has been “both fascinating and challenging” for study.

The prevalence of HCM in the adult population is approximately one in 500, Dr Ho added.

“But we know in HCM that LVH is not always unexplained or rather oftentimes can be explained by underlying genetic changes. So genetic testing is required in about 30 per cent of all-comers with a clinical diagnosis of HCM,” she said.

“Variants and sarcomere genes are most definitively and frequently associated with HCM.”

In recent times, much has been learned about the underlying mechanics and mechanisms of HCM and the development of new and effective therapies have reignited the field, she said.

“The leading theory about HCM pathophysiology is that the myosin is super activated, so that there are too many myosin heads interacting at any given point with actin filaments,” Dr Ho stated.

Clinical trials of cardiac myosin inhibitors (CMIs) have been highly successful for obstructive HCM and are transforming the management of symptomatic, obstructive HCM, Dr Ho stated.

She quoted a number of trials involving CMIs, including EXPLORER-HCM (mavacamten), VALOR-HCM (mavacamten), and SEQUOIA-HCM (aficamten), which demonstrated improved cardiac function.

“They [CMIs] provide robust evidence from randomised control trials [RCTs] to guide management and this is the first time we’ve had RCT evidence to guide our management of HCM. They’ve been successful in improving feel and function.”

She pointed out that drugs in this class were approved by the Food and Drug Administration in the US in 2022 and the European Medicines Agency in 2023.

The findings have been highlighted in the European Society of Cardiology management guidelines update of HCM in 2023.

Mavacamten has yet to be approved for reimbursement in Ireland by the National Centre for Pharmacoeconomics and is not widely available here, however. 

The recent MAPLE-HCM trial was another landmark moment in the treatment of HCM, Dr Ho noted. The trial concluded that aficamten monotherapy was superior to metoprolol monotherapy for HCM.

Dr Ho said the trial “led us to challenge the status quo and question how good traditional first-line therapies really are in treating obstructive HCM”.

“Beta-blockers may not provide meaningful benefit in obstructive HCM… and may not be as well tolerated as believed.

“Evidence is now available to consider using cardiac myosin inhibitors as first-line therapy.”

Moving to the treatment of non-obstructive HCM (nHCM), Dr Ho said the future of CMIs was “more complex and heterogeneous”, based on data available from trials to date.

Exercise for patients with HCM and recommendations in this area have changed in recent years, Dr Ho told the meeting.

In 2024, US guidelines were updated to state that “universal restriction from vigorous physical activity or competitive sports is not indicated”. Dr Ho also highlighted developments in targeting early stage HCM and gene therapy.