in pictures and a few words
What it is and why it matters
Aficamten is a medicine for adults whose thickened heart wall itself blocks the outflow of blood. It is prescribed when symptoms persist on usual treatment.
- It is the second medicine of this type; it was approved in the US in December 2025
- It works the same way as the first one, mavacamten, but is easier to control
- It doesn’t cure the disease but keeps its manifestations under control while it is taken
What happens in the heart
In this disease the heart muscle contracts too forcefully. The thickened septum, together with a valve, blocks the blood’s way out into the aorta — the body’s main vessel.
- Hence breathlessness, chest pain and fainting, especially on exertion
How the medicine works
The heart muscle has proteins that latch onto each other and make it contract. Aficamten reduces the number of excess couplings.
- The heart contracts more moderately and relaxes better
- The obstruction to blood outflow becomes smaller
Why it is easier to control
The main difference from mavacamten is controllability. Aficamten reaches its working level in the blood faster and leaves the body faster.
- The dose can be adjusted more often and more flexibly
- If the heart weakens too much, the effect wears off faster
- This doesn’t mean “better”: the two medicines have not been compared directly
What the trial showed
Aficamten was tested in people with symptoms of this disease and compared with a dummy pill.
- Exercise capacity was measured on an exercise test: how much oxygen the body takes in at peak
- This is an objective measure: it does not depend on how you feel
Tested in people. Tested in people: exercise capacity on aficamten was better than on the dummy pill.
Heart ultrasound is a must
The medicine weakens the heart’s squeeze — that is both its purpose and its risk. So the heart is checked regularly by ultrasound.
- They check how strongly the heart pushes blood out
- If too weakly, the dose is lowered or treatment is paused
- The medicine leaving the body quickly makes this easier but doesn’t replace the checks
Place in treatment
Basic treatment usually comes first, and if symptoms and narrowing persist, a medicine of this type is discussed. But in a study, as the first medicine, aficamten helped more than the beta blocker metoprolol; its place in treatment is decided by the cardiologist.
- Basic treatment is beta blockers or verapamil
- Aficamten does not remove the need for cardiologist follow-up
- If medicines haven’t helped and narrowing is severe — a procedure on the septum in an experienced centre
Long-term treatment
The disease is written in the genes. The medicine keeps its manifestations — narrowing and symptoms — under control while it is taken.
- After stopping, the original state returns
- This is not a reason to refuse treatment
- But treatment is long-term and needs regular follow-up
Who should see a doctor first
Aficamten is prescribed by a cardiologist based on heart ultrasound. Tell your doctor about all the medicines you take and about plans for pregnancy.
- Some medicines change its effect via the liver: the dose is changed, and sometimes they can’t be combined
- An infection or a rhythm disturbance can temporarily weaken the heart — treatment is reviewed
- Women who can become pregnant need contraception
Important. Pregnancy is a contraindication for this medicine.
In one sentence
Aficamten reduces the excessive squeeze of a thickened heart and the obstruction to blood outflow; it is easier to control than the first medicine of this type, but heart ultrasound and cardiologist follow-up are mandatory.
In brief
The mechanism is mavacamten's
In hypertrophic cardiomyopathy the heart muscle contracts excessively: the fraction of myosin ready to engage actin is increased. The thickened septum together with the mitral valve blocks outflow into the aorta — obstruction follows, and with it breathlessness, chest pain and syncope.
Cardiac myosin inhibitors reduce the number of those couplings. The heart contracts more moderately, relaxes better and the outlet obstruction eases.
The mechanics are covered in the mavacamten guide; here we focus on what the second generation changes.
What the second generation changed
| Mavacamten | Aficamten | |
|---|---|---|
| FDA approval | April 2022 | December 2025 |
| Half-life | Long | Shorter |
| Time to steady state | Slower | Faster |
| Titration steps | Less frequent | More frequent, more flexible |
| Reversibility if over-suppressed | Slower | Faster |
| Pivotal trial | EXPLORER-HCM | SEQUOIA-HCM |
The practical meaning of these differences is one word: controllability. When a drug lowers cardiac contractility, being able to correct course quickly matters. A shorter half-life means both faster dose finding and faster resolution of an unwanted drop in ejection fraction.
This does not make aficamten "better" — no head-to-head trials have been conducted between the two, and such claims would not be supportable.
What SEQUOIA-HCM showed
▸SEQUOIA-HCM (New England Journal of Medicine, 2024) — a phase 3 trial in patients with the symptomatic obstructive form. Aficamten improved peak oxygen uptake during exercise compared with placebo [1].
Peak oxygen uptake is an objective measure of capacity obtained during exercise testing. It does not depend on how the patient rates their own wellbeing, which is what makes it a valuable endpoint.
▸MAPLE-HCM (JACC: Heart Failure, 2026) is a separate trial that compared aficamten not with placebo but with the beta blocker metoprolol. Peak oxygen uptake improved more on aficamten — both in patients who had been taking beta blockers before enrolment and in those who had not [2].
Monitoring and safety
The requirements match the class:
▸echocardiography before starting, during titration and regularly thereafter — ejection fraction is the parameter watched; ▸if ejection fraction falls below threshold, the dose is reduced or treatment paused; ▸pregnancy is a contraindication; ▸hepatic enzyme interactions require a review of current therapy before prescribing; ▸intercurrent illness (infection, arrhythmia) can temporarily lower contractility — therapy is reassessed.
Where it belongs in treatment
In MAPLE-HCM, aficamten outperformed metoprolol as the first agent; its place in treatment is decided by the cardiologist. The usual sequence:
▸beta blockers or verapamil as baseline therapy; ▸with persistent symptoms and obstruction — discussion of a myosin inhibitor; ▸where drugs fail and obstruction is severe — septal myectomy or alcohol ablation in an experienced centre.
The choice between mavacamten and aficamten rests with the cardiologist: availability, convenience of monitoring and the clinical picture.
Summary
▸The second drug of the class, approved in December 2025. ▸Mechanism identical to mavacamten: fewer actin-myosin bridges, less obstruction. ▸The difference is controllability: shorter half-life, more flexible titration, faster reversibility. ▸SEQUOIA-HCM: improved peak oxygen uptake versus placebo. ▸Echocardiography is mandatory — the class risk has not gone away. ▸No head-to-head comparison with mavacamten — "better" cannot be claimed, "easier to titrate" can.
The diagnosis and management can be discussed at a consultation; the product can be ordered here.
References
1. Maron MS, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy (SEQUOIA-HCM). N Engl J Med. 2024;390(20):1849–1861. PMID 38739079
2. Dominguez F, et al. Efficacy of aficamten vs metoprolol according to pretrial beta-blocker treatment in obstructive hypertrophic cardiomyopathy: Insights From MAPLE-HCM. JACC Heart Fail. 2026. PMID 42667283
3. Olivotto I, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM). Lancet. 2020;396(10253):759–769. PMID 32871100
4. MYQORZO (aficamten) US Prescribing Information, Cytokinetics.
Key facts
- Aficamten (brand name Myqorzo, Cytokinetics) is the second cardiac myosin inhibitor of its class, approved by the FDA on 19 December 2025 — the most recent approval in this line.
- The mechanism matches mavacamten's: it reduces the fraction of myosin ready to engage actin, so the heart contracts less forcefully, relaxes better and outflow tract obstruction eases. The mechanics are covered in detail in the [mavacamten guide](/en/blog/mavacamten-camzyos-hypertrophic-cardiomyopathy).
- The main difference is pharmacokinetic. A shorter half-life and faster attainment of steady state mean the dose can be changed more often, and if contractility falls too far the effect wears off faster.
- SEQUOIA-HCM (New England Journal of Medicine, 2024): in patients with symptomatic obstructive hypertrophic cardiomyopathy, aficamten improved peak oxygen uptake during exercise compared with placebo.
- In MAPLE-HCM (2026), aficamten improved peak oxygen uptake more than the beta blocker metoprolol, regardless of prior beta blocker use.
- Monitoring is identical and equally mandatory: echocardiography with ejection fraction assessment before starting, during titration and regularly thereafter. Excessive suppression of contractility remains the class risk.
- No head-to-head trials exist between aficamten and mavacamten. Claims that one is "better" or "more effective" are not supportable — the difference lies in ease of dose management.
- Indication: symptomatic obstructive hypertrophic cardiomyopathy in adults whose standard therapy provides insufficient relief.
- As with mavacamten, pregnancy is a contraindication, and combination with strong hepatic enzyme inhibitors or inducers requires dose revision.
- In MAPLE-HCM, aficamten outperformed metoprolol as the first agent; its place in treatment is decided by the cardiologist, and the drug does not remove the need for cardiology follow-up.
