Mavacamten is an oral selective and reversible cardiac myosin inhibitor.

Read more: Specific cardiomyopathies – hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy there is excessive growth and overactivity of myocytes. The protein myosin is very important for the contraction of myocytes. In these patients the myosin is overactive. This causes an increased contractility and a decreased relaxation of the myocytes. In some of these patients this leads to a narrowing or obstruction of the outflow tract of the left ventricle below the aortic valve. This is the LVOT, the left ventricular outflow tract. These patients then have an obstructive hypertrophic cardiomyopathy. Here there is an accelerated blood flow through the LVOT and an increased pressure gradient, which can be measured with echocardiography.

Myosin inhibition decreases contractility and improves relaxation of overactive myocytes. LVOT obstruction and the pressure gradient across the LVOT decrease, which increases cardiac output and decreases intracardiac pressure, reduces dyspnea on exertion and improves prognosis.

Trail : EXPLORER-HCM and VALOR-HCM

• Improving exercise capacity, reducing symptoms and improving quality of life.
• Reducing the need for invasive treatment (septal reduction therapy by surgical septal myomectomy or percutaneous alcoholic septal ablation).

Adult patients with hypertrophic obstructive cardiomyopathy and persistent symptoms of dyspnea on exertion (NYHA II-III) and an increased pressure gradient across the LVOT of ≥ 50 mmHg (at rest or after provocation (e.g. stress echocardiography), despite either previous therapy with a β-blocker and/or a non-dihydropyridine calcium antagonist (verapamil or diltiazem), or a contraindication or intolerance to these treatments.

From September 1, 2024, mavacamten (Camzyos) is reimbursed in Belgium for the treatment of obstructive hypertrophic cardiomyopathy.

The reimbursement criteria in Belgium are:

1. Camzyos must be initiated by a cardiologist working in a multidisciplinary center for the treatment of heart failure (see list at: https://www.heartfailure.be/en/medical-centers-2/ ).
2. Camzyos can only be delivered by the hospital pharmacy.
3. Clinical criteria:
   • NYHA class II or III.
   • Left ventricular wall thickness ≥ 15 mm (or ≥ 13 mm in positive family history).
   • Left ventricular ejection fraction (LVEF) ≥ 55% (by echocardiography).
   • At least one measurement of left ventricular outflow tract (LVOT) peak gradient ≥ 50 mmHg (at rest or after provocation (e.g. with stress echocardiography)), and with Valsalva manoeuvre an LVOT gradient ≥ 30 mmHg at the start of treatment.
   • Resting oxygen saturation ≥ 90%.
4. The patient must have been previously treated with a beta blocker or a calcium channel blocker (verapamil or diltiazem). This treatment should be continued unless intolerance occurs.
5. Genotyping for cytochrome P450 (CYP) 2C19 (CYP2C19) is required to determine the appropriate dose of Camzyos.
6. Before starting treatment, women of childbearing potential must have a negative pregnancy test.

Dose in adults: 2.5 mg, 5 mg, 10 mg or 15 mg orally once daily, depending on the CYP2C19 phenotype and the evolution of the peak gradient across the LVOT. The dose is determined by the cardiologist.

• Slow metabolizers : start with 2.5 mg per day, increasing to a maximum of 5 mg per day.
• Intermediate, normal to fast metabolizers: start with 5 mg per day, increasing to 15 mg per day if necessary.

After 4 and 8 weeks, check the effects on symptoms and cardiac function (echocardiography: LV function and evolution of the gradient across the LVOT, also with Valsalva manoeuvre).

Consider discontinuing treatment if no clinical improvement occurs after 4-6 months despite the maximum tolerated dose.

• Dizziness
• Dyspnea
• LV dysfunction with LVEF decrease <50%
• Syncope

• LVEF < 55% prior to initiation of therapy.
• LVEF decline <50% during therapy.
• Pregnancy and lactation. Good contraception is necessary.
• Certain combinations with other medicines. See interactions above and in the package leaflet.