The European Medicines Agency has required pre-treatment genotyping of CYP2C19 to determine the initial and maximum dosage, in order to avoid overexposure to mavacamten associated with a decrease in ventricular ejection fraction below 50% in slow metabolisers of CYP2C19 (AUC multiplied by 3.4). The study is a requalification for the search for DNA samples obtained during treatment in order to genotype the genes of interest.The primary objective of the study is to estimate, for each of the CYP2C19 phenotypes of interest determined by genotyping (ultra-rapid, rapid, normal/extensive and intermediate metabolisers), the proportion of patients who are non-responders to mavacamten at each time point (D0, Week 4, Week 8, Week 12 and Week 24 in the treatment of HCM). This is a multicentre (3 centres which are hospitals of APHP) study aiming to include 300 patients with obstructive hypertrophic cardiomyopathy treated with Mavacamten who underwent or are undergoing CYP2C19 genotyping at the start of treatment. The inclusion period is 36 months and the follow-up period is 6 months. The total duration of the study is 42 months.
- Patients aged ≥18 years
Diagnosis of obstructive hypertrophic cardiomyopathy (OHCM), based on the guidelines of the European Society of Cardiology (Arbelo et al. 2023), with unexplained left ventricular hypertrophy and a maximum LVOT gradient ≥ 50 mmHg at rest, or after Valsalva manoeuvre or exercise at the time of diagnosis, and an LVOT gradient with Valsalva manoeuvre ≥ 30 mmHg at selection
With cardiac symptoms defined as NYHA class II/III, persistent despite background treatment (beta-blockers or calcium channel blockers)
LVEF ≥55% at the start of treatment with mavacamten
Minors
Adults under guardianship (legal guardianship and curatorship) or judicial protection
Pregnant or breastfeeding women
300 patients with obstructive hypertrophic cardiomyopathy treated with Mavacamten who underwent or are undergoing CYP2C19 genotyping at the start of treatment.
Cohort
Other
Not listed
Response rate to Mavacamten treatment
Proportion of patients responding to mavacamten (LVEF \>55% and LVOT gradient at Valsalva \<30 mL/min) according to different CYP2C19 and CYP3A phenotypic groups at 12 and 24 weeks, evaluated by echocardiography
Response rate to Mavacamten treatment in the above-mentioned populations
Echocardiographic parameters (LVOT gradients at rest and Valsalva, and LVEF) according to different CYP2C19 and CYP3A phenotypic groups at 0, 4, 8, 12 and 24 weeks: 1. Patients who have undergone invasive therapy for obstruction 2. According to NYHA class 3. In patients treated with beta-blockers
Response rate to Mavacamten treatment in the general population and in the above-mentioned populations
Steady-state daily dose of mavacamten in the general population and according to CYP2C19 and CYP3A patient phenotypic groups, at 12 and 24 weekInfluence of steady-state daily dose of mavacamten according to CYP2C19 and CYP3A phenotypic groups and co-treatments: 1. Co-administration of a strong to moderate CYP2C19 inhibitor 2. Co-administration of a strong to moderate CYP3A4 inhibitor 3. Co-administration of a strong to moderate CYP2C9 inhibitor
Description of cardiac and other adverse effects (excluding reduced LVEF) in the general population and in the above-mentioned populations
Description of cardiac and other adverse effects (excluding reduced LVEF) in the general population and in the above-mentioned populations (points 1a, 1b, 1c) according to: 1. Co-administration of a strong to moderate CYP2C19 inhibitor 2. Co-administration of a strong to moderate CYP3A4 inhibitor 3. Co-administration of a strong to moderate CYP2C9 inhibitor
Variation in dosage of Mavacamten at weeks 4, week 8, week 12 and week 24 according to the different populations
Variation in dosage of Mavacamten at weeks 4, week 8, week 12 and week 24 according to the different populations : a. Patients who have undergone invasive therapy for obstruction b. According to NYHA class c. In patients treated with beta-blockers
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