More oxygen available means the heart is working better
For generations, a thickening of the heart muscle has stolen ordinary life from the young and the otherwise healthy — leaving them breathless at the mailbox, at risk of sudden death on the playing field. Now, a new investigational drug called aficamten has demonstrated in a large international trial that it can meaningfully restore the body's capacity to use oxygen during exertion, offering patients with obstructive hypertrophic cardiomyopathy a path back toward the unremarkable rhythms of daily existence. The finding, published in the New England Journal of Medicine and presented in Lisbon in May 2024, suggests medicine may be entering a new chapter in its long struggle with one of the most quietly devastating inherited conditions of the heart.
- Hypertrophic cardiomyopathy affects one in 500 people and remains a leading cause of sudden cardiac death in young athletes — a disease that strikes without warning and offers no cure.
- For decades, patients faced a stark choice between invasive surgery and, more recently, a first-generation drug burdened by serious side effects and demanding monitoring requirements.
- In a Phase 3 trial of 282 adults, aficamten improved peak oxygen uptake by 1.7 ml/kg/min over placebo — a modest number that translates directly into climbing stairs, doing housework, and living without constant breathlessness.
- Higher peak oxygen use is not merely a comfort metric; it correlates with lower rates of heart failure, reduced need for transplant, and improved survival overall.
- OHSU, which enrolled more patients in this trial than any other center, is already running four additional aficamten studies across different HCM populations, including children, signaling strong institutional confidence in the drug's trajectory toward FDA approval.
A drug called aficamten has shown it can meaningfully improve oxygen use during exercise in patients with obstructive hypertrophic cardiomyopathy — a finding that may reshape how medicine approaches one of the most common inherited heart conditions, and one of the quietest killers of young people.
The results come from an international trial of 282 adults, published in the New England Journal of Medicine and presented at the European Society of Cardiology's Heart Failure conference in Lisbon in May 2024. Oregon Health & Science University enrolled more participants than any other center. Patients taking aficamten — developed by Cytokinetics — used 1.7 milliliters of oxygen per kilogram of body weight per minute more than those on placebo. For people who struggle to walk to the mailbox or climb a flight of stairs without becoming breathless, that difference is felt in daily life.
HCM thickens the heart muscle and obstructs blood flow. It affects roughly one in 500 people, is usually inherited, and has no cure — only management. It is also a leading cause of sudden cardiac death in otherwise healthy young athletes. For years, surgery to remove excess heart muscle was the primary option. In 2022, the FDA approved mavacamten, the first drug targeting the condition's root cause, but it carries risks of heart failure, interacts with many common medications, and demands intensive monitoring.
Aficamten appears to offer a cleaner path. Dr. Ahmad Masri of OHSU's Knight Cardiovascular Institute, one of the paper's authors, notes that improved oxygen uptake directly correlates with survival — lower risk of heart failure, less need for transplant, reduced mortality. OHSU is already conducting four additional aficamten trials across different HCM forms and patient populations, including children, reflecting confidence that the drug will reach approval and expand what treatment can look like for the half-million Americans living with this condition.
A drug called aficamten has shown it can meaningfully improve how much oxygen patients can use during exercise—a finding that could reshape how doctors treat a common inherited heart condition that kills otherwise healthy young people without warning.
The discovery comes from a large international trial involving 282 adults with obstructive hypertrophic cardiomyopathy, or HCM, a disease that thickens the heart muscle and makes it harder for blood to flow out of the organ. Oregon Health & Science University enrolled 19 of those patients, more than any other trial center. The results, published in the New England Journal of Medicine and presented at the European Society of Cardiology's Heart Failure conference in Lisbon in May 2024, show that patients who took aficamten—developed by the company Cytokinetics—were able to use 1.7 milliliters of oxygen per kilogram of body weight per minute more than those who received a placebo.
That number might sound abstract until you consider what it means in practice. People with HCM struggle with everyday life. Walking to the mailbox, climbing stairs, doing housework—these ordinary tasks leave them breathless and exhausted. The disease affects roughly one in 500 people and is one of the leading causes of sudden cardiac death in young athletes and otherwise healthy youth. It's usually inherited, passed down through families as a genetic mutation. There is no cure, only management.
For decades, the only real option was surgery: removing excess heart muscle to restore blood flow. In 2022, the FDA approved a drug called mavacamten, the first medication designed to address the root cause of obstructive HCM. But mavacamten comes with complications. It can increase the risk of heart failure, it interferes with many common medications, and patients taking it require intensive monitoring. Aficamten appears to offer a different path.
Dr. Ahmad Masri, a cardiologist at OHSU's Knight Cardiovascular Institute and one of the paper's authors, frames the significance plainly: when patients have more oxygen available during physical activity, they can do the things most of us take for granted without thinking. "Our latest clinical trial results suggest aficamten is a promising treatment for HCM," he said. The improvement in oxygen uptake matters because it directly correlates with survival. Higher peak oxygen use means lower risk of heart failure, lower need for transplants, and lower mortality overall.
OHSU is not waiting to see what happens next. The institution is already running four additional aficamten trials, testing the drug in different forms of HCM and in different patient populations, including children. This suggests confidence that the drug will eventually reach FDA approval and become available beyond the research setting. For a disease that has limited patients to surgery or a problematic medication for so long, the prospect of another option—one that might work better and carry fewer risks—represents a genuine shift in what's possible.
Masri captures the moment well: "This is an exciting time for treating HCM. While we continue to offer traditional surgical and procedural therapies for HCM, we are now also able to offer patients other treatment options." The work ahead is to prove aficamten can deliver on its promise, and to understand whether it might eventually become the preferred first-line treatment for a disease that has constrained the lives of half a million Americans.
Notable Quotes
By having more oxygen available during exercise, patients with obstructive hypertrophic cardiomyopathy can more easily walk, perform household chores, and do other everyday tasks.— Dr. Ahmad Masri, cardiologist at OHSU Knight Cardiovascular Institute
This is an exciting time for treating HCM. We are now able to offer patients other treatment options: therapies that were recently approved by the FDA and investigational therapies available through clinical trials.— Dr. Ahmad Masri
The Hearth Conversation Another angle on the story
Why does oxygen uptake matter so much for someone with this heart condition?
Because HCM thickens the heart muscle and restricts blood flow. When blood can't move efficiently, the body can't deliver oxygen to muscles during exercise. More oxygen available means the heart is working better—it's not just about feeling less tired, it's about survival.
The improvement was 1.7 milliliters per kilogram per minute. That sounds small.
In absolute terms, yes. But in a disease where patients can barely walk upstairs, that difference lets them do ordinary things. It's the difference between being housebound and being able to live.
You mentioned mavacamten was approved two years earlier. Why would doctors choose aficamten if it's newer?
Mavacamten works, but it has real drawbacks—it can trigger heart failure, it clashes with common medications, and patients need constant monitoring. If aficamten achieves similar results without those complications, it becomes the obvious choice.
OHSU is running four more trials. Does that mean aficamten isn't approved yet?
Correct. This Phase 3 trial is the final major hurdle before FDA review. The additional trials are testing it in children and other HCM variants to expand what the drug can treat. They're building the case for broader approval.
Who benefits most from this—the young athletes you mentioned?
They're one group, but HCM affects one in 500 people across all ages. Many don't know they have it until something catastrophic happens. For those diagnosed, this drug could mean the difference between a constrained life and a normal one.